International Journal of Molecular Sciences

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15 pages, 2565 KB

Open AccessArticle

Influence of Very Short-Term Sexual Abstinence on Basic Semen Parameters and Sperm Chromatin Status: A Preliminary Study

by Kamil Gill, Mariusz Łukaszuk, Tomasz Machałowski and Małgorzata Piasecka

Int. J. Mol. Sci. 2026, 27(11), 5046; https://doi.org/10.3390/ijms27115046 - 3 Jun 2026

Cited by 1 | Viewed by 2414

Abstract

Infertility is a rising global medical problem that affects 15–20% of reproductive-age couples. Importantly, a male factor contributes to this issue in 30–50% of cases. Abnormalities in semen parameters, particularly sperm genome integrity, are major causes of male infertility. Recent reports indicate that [...] Read more.

Infertility is a rising global medical problem that affects 15–20% of reproductive-age couples. Importantly, a male factor contributes to this issue in 30–50% of cases. Abnormalities in semen parameters, particularly sperm genome integrity, are major causes of male infertility. Recent reports indicate that the duration of sexual abstinence is a significant and easily modifiable factor that may influence semen quality. Therefore, this study was designed to evaluate the effects of very short-term sexual abstinence on standard semen parameters and sperm chromatin status. This study was conducted on semen samples obtained from adult men (n = 95) who were partners in couples with reproductive failure. Each participant provided two semen samples on the same day: the first after 2–7 days of sexual abstinence and the second after one hour of sexual abstinence. Semen analysis was performed according to the World Health Organization (2021) guidelines, and the sperm chromatin status was determined using three complementary assays: sperm chromatin dispersion test (SCDt), and aniline blue (ABt) and toluidine blue (TBt) stains. One-hour sexual abstinence significantly reduced the following parameters: ejaculate volume (median: 3.50 mL vs. 1.50 mL), total sperm count (median: 78.30 × 10⁶ sperm vs. 29.00 × 10⁶ sperm cells), number of sperm cells with DNA fragmentation (SDF index; SCDt; median: 19.00% vs. 16.50%), prevalence of subjects with an SDF index > 20% (44.18% vs. 24.46%) and odds ratio for an SDF index > 20% (OR = 0.4568). No significant differences were found in the results of the ABt or TBt. Our data indicate that a very short period of sexual abstinence negatively affects ejaculate volume and total sperm count but positively influences sperm genome integrity. Importantly, the sperm chromatin dispersion test can be considered a useful tool for verifying sperm DNA quality. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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18 pages, 4363 KB

Open AccessArticle

Modulation of NF-κB and TLR Signaling Pathways and Complement Components in Ovine Maternal Thyroid During Early Pregnancy

by Yaqi Zhang, Jingjing Li, Fei Yang, Chenxu Wu, Leying Zhang and Ling Yang

Int. J. Mol. Sci. 2026, 27(11), 4791; https://doi.org/10.3390/ijms27114791 - 26 May 2026

Viewed by 490

Abstract

Pregnancy modulates the function of the thyroid gland to facilitate maternal immune tolerance, and nuclear factor kappa B (NF-κB) subunits, the IκB family, and toll-like receptors (TLRs) and complement signaling pathways may be implicated in maternal thyroid immunoregulation. However, it is unclear whether [...] Read more.

Pregnancy modulates the function of the thyroid gland to facilitate maternal immune tolerance, and nuclear factor kappa B (NF-κB) subunits, the IκB family, and toll-like receptors (TLRs) and complement signaling pathways may be implicated in maternal thyroid immunoregulation. However, it is unclear whether early pregnancy modulates the expression of NF-κB subunits, the IκB family, TLRs, and complement components in the maternal thyroid. The objective of this study was to analyze the effects of early pregnancy on the expression of genes and proteins of these signaling pathways in the maternal thyroid in ewes. In this study, ovine thyroids (n = 6 for each group) were sampled on day 16 of the estrous cycle (N16) and on days 13, 16, and 25 of pregnancy (P13, P16, and P25) with one conceptus. The ewes had an average weight of 41 kg and a body condition score of 3. The mRNA and protein expression of the NF-κB subunits and IκB family were analyzed by RT-qPCR, western blot, and immunohistochemistry. The results showed that the expression of all NF-κB subunits, the IκB family, and TLRs, as well as C1q, C1r, C2, C4a, C5b, and C9, peaked at P16 among these four stages (p < 0.05). In addition, C1s expression was greater at N16 and P16 than at P13 and P25 (p < 0.05), and C3 expression was stronger at P16 and P25 compared to N16 and P13 (p < 0.05). In conclusion, early pregnancy modulates the expression of NF-κB subunits, the IκB family, TLRs, and complement components in the ovine thyroid at both the mRNA and protein levels, which may be essential for maternal thyroid adaptation to pregnancy and beneficial for the prevention of pregnancy-related thyroid diseases in ewes. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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14 pages, 2338 KB

Open AccessArticle

Estrogen-Mediated Regulation of Fam3d in Mouse Uterus During the Estrous Cycle

by Hyukjung Kim, Byeongseok Kim, Joohee Kim, Yeonju Suh, Jimin Lee, Sangok Park, Man Ryul Lee, Hoi Chang Lee and Youngsok Choi

Int. J. Mol. Sci. 2025, 26(24), 11840; https://doi.org/10.3390/ijms262411840 - 8 Dec 2025

Cited by 3 | Viewed by 1419

Abstract

In mice, the uterus undergoes dynamic changes regulated by estrogen and progesterone during the estrous cycle. Proper regulation of these changes is critical for successful pregnancy. The Family with sequence similarity 3 (Fam3) gene family, comprising Fam3a, Fam3b, Fam3c, and [...] Read more.

In mice, the uterus undergoes dynamic changes regulated by estrogen and progesterone during the estrous cycle. Proper regulation of these changes is critical for successful pregnancy. The Family with sequence similarity 3 (Fam3) gene family, comprising Fam3a, Fam3b, Fam3c, and Fam3d, encodes cytokine-like proteins, but their uterine roles remain unclear. This study examined Fam3 expression in the mouse uterus across the estrous cycle and assessed estrogen-dependent regulation. RNA-seq analysis revealed increased Fam3b, Fam3c, and Fam3d expression during proestrus and estrus. Notably, Fam3d showed dynamic regulation, peaking in these stages. To test estrogen regulation, estradiol was administered to ovariectomized mice, showing maximal Fam3d expression at 24 h post-injection. ERα antagonist treatment blocked this induction, indicating ERα-mediated regulation. Immunofluorescence localized FAM3D to the cytoplasm of luminal and glandular epithelia, especially in the apical region, with no stromal or nuclear expression. These findings suggest that estrogen and Erα (Estrogen receptor alpha) signaling control Fam3d expression, implicating FAM3D in uterine epithelial function. This study provides novel insights into Fam3d’s role in uterine physiology and a foundation for exploring its function in reproduction. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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14 pages, 12158 KB

Open AccessArticle

ESR1 Regulates Fecundity and Functions in Sheep Endometrial Stromal Cells

by Kang Li, Xiaoxiao Gao, Zhibo Wang, Dongxu Li, Jiahe Guo, Feng Wang and Tianlong Guo

Int. J. Mol. Sci. 2025, 26(23), 11410; https://doi.org/10.3390/ijms262311410 - 25 Nov 2025

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Abstract

Endometrial stromal cell (ESC) plasticity is critical to embryo survival and conceptus elongation; however, their genetic regulation remains unclear. To elucidate the molecular mechanisms by which ESR1 regulates sheep fecundity through endometrial function, we investigated the effects of ESR1 on ovine ESCs in [...] Read more.

Endometrial stromal cell (ESC) plasticity is critical to embryo survival and conceptus elongation; however, their genetic regulation remains unclear. To elucidate the molecular mechanisms by which ESR1 regulates sheep fecundity through endometrial function, we investigated the effects of ESR1 on ovine ESCs in vitro. Tissue distribution analysis revealed elevated ESR1 expression in the reproductive organs, particularly the endometrium, compared with that in non-reproductive tissues. Both ESR1 mRNA and its encoded ERα protein were significantly upregulated in the endometrium of high-fecundity Hu sheep compared to those in the endometrium of low-fecundity Hu sheep. Given the specific localisation of ERα in ESCs, we examined the functional roles of ESR1 in these cells in vitro. ESR1 knockdown in ESCs inhibited cell proliferation and induced apoptosis, concomitant with increased Caspase3 and Caspase9 mRNA expression. Furthermore, ESR1 interference triggered G0/G1-phase cell cycle arrest via the upregulation of P53 and P21 and significantly impaired cell migration capacity. Collectively, these results demonstrate that ESR1 critically regulates ESC proliferation, apoptosis, cell cycle progression, and migration. Our findings establish ESR1 as a key determinant of sheep fecundity and provide mechanistic insights into the high reproductive efficiency of Hu sheep. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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17 pages, 580 KB

Open AccessArticle

Association of BMAL1 and CLOCK Gene Polymorphisms with Preeclampsia Risk with Subtype Analysis

by Fan Xia, Peiwen Wang, Ziye Li, Jiehua Wei, Jianhui Wei, Yuhang Wu, Chu Liu, Shanyu Lin, Suyan Guo, Linbin He, Mengshi Chen, Lizhang Chen and Tingting Wang

Int. J. Mol. Sci. 2025, 26(21), 10797; https://doi.org/10.3390/ijms262110797 - 6 Nov 2025

Cited by 3 | Viewed by 1456

Abstract

Preeclampsia (PE), a major cause of maternal and perinatal morbidity, is a hypertensive pregnancy disorder with poorly defined pathogenesis. While dysregulation of core circadian genes including brain and muscle ARNT-like 1 (BMAL1; also termed ARNTL) and circadian locomotor output cycles [...] Read more.

Preeclampsia (PE), a major cause of maternal and perinatal morbidity, is a hypertensive pregnancy disorder with poorly defined pathogenesis. While dysregulation of core circadian genes including brain and muscle ARNT-like 1 (BMAL1; also termed ARNTL) and circadian locomotor output cycles kaput (CLOCK) has been implicated in PE, the contribution of their genetic polymorphisms to PE remains unclear. In this case–control study, polymorphisms in BMAL1 and CLOCK were genotyped using MassARRAY in 202 PE patients (97 early-onset [eoPE], 105 late-onset [loPE]) and 400 controls. Following genotyping and linkage disequilibrium-pruning (r² > 0.8) to retain representative tag SNPs, the final set for association analysis comprised three non-redundant BMAL1 SNPs (rs4757144, rs11022780, rs969485) and one CLOCK SNP (rs1048004). After confounder adjustment, no significant associations were detected for CLOCK variants, whereas the BMAL1 rs11022780 variant demonstrated a significant protective effect against PE (TT vs. CC: OR = 0.26 [95% CI 0.09–0.78]; recessive model: OR = 0.25 [95% CI 0.09–0.74]), particularly in the eoPE subgroup. Expression quantitative trait locus (eQTL) analysis confirmed that this SNP correlated with BMAL1 mRNA expression in whole blood, and protein–protein interaction analysis highlighted BMAL1′s central role in circadian networks, implying a genetically influenced regulatory mechanism of PE through BMAL1 expression. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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15 pages, 2093 KB

Open AccessArticle

Sperm DNA Fragmentation Impairs Early Embryo Development but Is Not Predictive of Pregnancy Outcomes: Insights from 870 ICSI Cycles

by Tomasz Machałowski, Julita Machałowska, Kamil Gill, Maciej Ziętek, Małgorzata Piasecka, Grzegorz Mrugacz and Przemysław Ciepiela

Int. J. Mol. Sci. 2025, 26(16), 7923; https://doi.org/10.3390/ijms26167923 - 16 Aug 2025

Cited by 12 | Viewed by 14062

Abstract

Sperm DNA fragmentation (SDF) is increasingly regarded as a biomarker of male infertility, but its predictive value for intracytoplasmic sperm injection (ICSI) outcomes remains controversial. This retrospective cohort study analyzed 870 fresh single-blastocyst ICSI cycles performed between January 2023 and December 2024. SDF [...] Read more.

Sperm DNA fragmentation (SDF) is increasingly regarded as a biomarker of male infertility, but its predictive value for intracytoplasmic sperm injection (ICSI) outcomes remains controversial. This retrospective cohort study analyzed 870 fresh single-blastocyst ICSI cycles performed between January 2023 and December 2024. SDF was measured using the Sperm Chromatin Dispersion test and patients were categorized into low (SDF ≤ 20%, n = 664) and high (SDF > 20%, n = 206) groups. Higher SDF was significantly associated with reduced semen quality, lower fertilization rates, and poorer blastocyst development. In multivariable analysis, each 1% increase in SDF reduced the odds of achieving a fertilization rate > 80% by 1.6% (OR = 0.984, 95% CI: 0.971–0.997, p = 0.015) and decreased the chance of obtaining top-quality blastocysts on day 5 by 2.5% (OR = 0.975, 95% CI: 0.958–0.992, p = 0.004). A trend toward impaired day-3 embryo quality was observed (OR = 0.983, p = 0.068). No significant association was found with clinical pregnancy (OR = 0.989, p = 0.155), while the relationship with miscarriage was borderline (OR = 0.961, p = 0.053). These findings suggest that elevated SDF adversely impacts early embryological outcomes in ICSI, supporting its use as a prognostic tool during ART counseling. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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13 pages, 9208 KB

Open AccessArticle

Hormonal Signaling and Follicular Regulation in Normal and Miniature Pigs During Corpus Luteum Regression

by Sang-Hwan Kim

Int. J. Mol. Sci. 2025, 26(15), 7147; https://doi.org/10.3390/ijms26157147 - 24 Jul 2025

Cited by 1 | Viewed by 1378

Abstract

Reproductive efficiency in pigs is regulated by hormonal pathways that control follicular development at Day 15 of the estrous cycle, during corpus luteum regression. Miniature pigs are extensively employed as human-relevant models in biomedical research, yet their reproductive characteristics during mid-luteal regression remain [...] Read more.

Reproductive efficiency in pigs is regulated by hormonal pathways that control follicular development at Day 15 of the estrous cycle, during corpus luteum regression. Miniature pigs are extensively employed as human-relevant models in biomedical research, yet their reproductive characteristics during mid-luteal regression remain inadequately characterized, limiting assessments of their translational reliability. Differences in follicular morphology, hormonal signaling, and vascular development may underlie their lower fertility compared to conventional pigs. In this study, follicular development after corpus luteum formation was compared between conventional pigs and minipigs using histological staining, immunofluorescence, hormonal assays, and transcriptomic profiling. The expression of VEGF, mTOR, LH, FSH, PAPP-A, and apoptosis markers was evaluated across the granulosa and thecal regions. Differential gene expression was analyzed using microarray data followed by GO categorization. Minipigs exhibited smaller follicles, reduced vascularization, and lower VEGF and MMP activity compared to conventional pigs. Expression of LH and PAPP-A was higher in conventional pigs, while minipigs showed relatively elevated E2 and FSH levels. Transcriptomic data revealed greater upregulation of cell-survival- and angiogenesis-related genes in conventional pigs, including genes involved in IGF pathways. Apoptosis and poor extracellular matrix remodeling were more pronounced in minipigs. Minipigs demonstrated impaired follicular remodeling and weaker hormonal signaling after corpus luteum formation, which likely contributed to their reduced reproductive efficiency. Understanding these species differences can guide breeding strategies and fertility management in biomedical and agricultural settings. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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18 pages, 9131 KB

Open AccessArticle

The Primary Cultivation of Oogonial Stem Cells from Black Rockfish (Sebastes schlegelii): Morphology and Transcriptome Landscape

by Jingjing Zhang, Lei Lin, Shengyu Zhu, Yanming Zhang, Caichao Dong, Yu Yang, Yuyan Liu, Xuwen Cao, Yangbin He, Honglong Ji, Bo Meng, Qian Wang and Changwei Shao

Int. J. Mol. Sci. 2025, 26(14), 6772; https://doi.org/10.3390/ijms26146772 - 15 Jul 2025

Cited by 7 | Viewed by 1716

Abstract

Black rockfish (Sebastes schlegelii) is a marine ovoviviparous teleost that exhibits significant sexual dimorphism, with females growing faster and reaching larger sizes than males. Establishing stable oogonial stem cells (OSCs) is critical for understanding germline stem cell dynamics and facilitating all-female [...] Read more.

Black rockfish (Sebastes schlegelii) is a marine ovoviviparous teleost that exhibits significant sexual dimorphism, with females growing faster and reaching larger sizes than males. Establishing stable oogonial stem cells (OSCs) is critical for understanding germline stem cell dynamics and facilitating all-female breeding. In this study, we successfully isolated and cultured OSCs from S. schlegelii for 12 passages. These cells exhibited alkaline phosphatase activity, expressed germline marker genes (ddx4, cdh1, klf4), and maintained a diploid karyotype (2n = 48). Transcriptomic comparisons between early (P3) and late (P12) passages revealed significant metabolic dysfunction and cell cycle arrest in the late-passage cells. Specifically, the down-regulation of glutathione-related and glycolysis-related genes (gstm3, gstt1, mgst3, gsta1, gsta4, gsto1, gapdh) and key mitotic regulators (cdk1, chk1, cdk4, e2f3, ccne2, ccnb1) suggested that metabolic imbalance contributes to oxidative stress, resulting in cell cycle inhibition and eventual senescence. This study provides a marine fish model for investigating metabolism-cell cycle interactions in germline stem cells and lays the foundation for future applications in germ cell transplantation and all-female breeding. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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10 pages, 1123 KB

Open AccessArticle

Indoleamine 2,3-Dioxygenase Regulates Placental Trophoblast Cell Invasion

by Yoshiki Kudo and Jun Sugimoto

Int. J. Mol. Sci. 2025, 26(12), 5889; https://doi.org/10.3390/ijms26125889 - 19 Jun 2025

Cited by 2 | Viewed by 1190

Abstract

To clarify the physiological importance of the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase, in human pregnancy, we have studied how the expression of this enzyme controls extravillous cytotrophoblast invasion into the decidua. We have generated an Ishikawa cell line stably transfected with a plasmid [...] Read more.

To clarify the physiological importance of the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase, in human pregnancy, we have studied how the expression of this enzyme controls extravillous cytotrophoblast invasion into the decidua. We have generated an Ishikawa cell line stably transfected with a plasmid encoding indoleamine 2,3-dioxygenase under the control of a tetracycline inducible promoter. Using this Ishikawa cell line and extravillous cytotrophoblast cell line, HTR-8/SVneo, we developed a quantitative in vitro trophoblast invasion assay. When trophoblast cells were cultured on a layer of Ishikawa cells expressing indoleamine 2,3-dioxygenase, tryptophan degradation was enhanced and trophoblast cell invasion was suppressed. These findings suggest that indoleamine 2,3-dioxygenase expressed in the decidua may play a role in regulating trophoblast invasion. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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12 pages, 1113 KB

Open AccessArticle

Abnormally Increased Prolactin Levels in Women with Polycystic Ovarian Syndrome Are Associated with Risk of Obesity, Insulin Resistance and Prediabetes

by Vesselina Yanachkova and Teodora Stankova

Int. J. Mol. Sci. 2025, 26(9), 4239; https://doi.org/10.3390/ijms26094239 - 29 Apr 2025

Cited by 5 | Viewed by 9312

Abstract

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine condition in women of reproductive age, characterized also by insulin resistance, affecting both obese and non-obese individuals. Hyperprolactinemia in patients with PCOS may additionally aggravate the decline in insulin sensitivity, attributable to prolactin lipogenic effects [...] Read more.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine condition in women of reproductive age, characterized also by insulin resistance, affecting both obese and non-obese individuals. Hyperprolactinemia in patients with PCOS may additionally aggravate the decline in insulin sensitivity, attributable to prolactin lipogenic effects and influence on metabolic profile. Therefore, this study aimed to investigate the serum levels of prolactin in women with PCOS and their associations with obesity, insulin resistance and prediabetes. A retrospective monocentric study was performed using the electronic database of 157 women diagnosed with PCOS. Serum prolactin, BMI, complete glucose-insulin profile and insulin resistance indices following OGTT were determined. The women with hyperprolactinemia (40.8%) had significantly higher BMI (p = 0.007), fasting glucose (p = 0.003), insulin levels (p < 0.001) and HOMA-IR (p < 0.001). The women with PCOS categorized as overweight/obese (47.1%), insulin resistant (68.8%), having impaired fasting glycaemia (28.7%) and prediabetes (36.3%) showed significantly higher levels of prolactin compared to the respective counterparts. Consequently, higher prolactin levels were significantly associated with an elevated risk of development of overweight/obesity (OR 2.59; 95% CI: 1.34–4.97, p = 0.004), insulin resistance (OR 3.33; 95% CI: 1.54–7.19, p = 0.002) and prediabetes (OR 1.98; 95% CI: 1.02–3.85, p = 0.043) in women with PCOS. Our results suggest that hyperprolactinemia might be a pathophysiological link between obesity, insulin resistance, and carbohydrate metabolism impairments in patients with PCOS. Increased prolactin levels may serve as an additional indicator of insulin resistance and even further exacerbate it in women with PCOS. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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14 pages, 4642 KB

Open AccessArticle

DNA Methylation Patterns Provide Insights into the Epigenetic Regulation of Intersex Formation in the Chinese Mitten Crab (Eriocheir sinensis)

by Shu-Jian Fang, Shu-Cheng Shao, Meng-Qi Ni, Ya-Nan Yang and Zhao-Xia Cui

Int. J. Mol. Sci. 2025, 26(7), 3224; https://doi.org/10.3390/ijms26073224 - 30 Mar 2025

Cited by 1 | Viewed by 1841

Abstract

DNA methylation is a form of epigenetic regulation that plays an important role in regulating gene expression of organisms. However, the DNA methylation pattern of intersex crabs has not yet been clarified. In order to reveal the DNA methylation in intersex Eriocheir sinensis [...] Read more.

DNA methylation is a form of epigenetic regulation that plays an important role in regulating gene expression of organisms. However, the DNA methylation pattern of intersex crabs has not yet been clarified. In order to reveal the DNA methylation in intersex Eriocheir sinensis, this study investigated the genome-wide DNA methylation profiles of female, male, and intersex individuals. The similar results across samples showed that the levels of cytosine methylation in the CG context were significantly higher than that in the CHG and CHH contexts. The methylation levels in the promoter region were higher than those in other functional element regions. We screened 149 differentially methylated genes (DMGs) in the promoter region between female and intersex crabs and 110 DMGs between male and intersex crabs. Three core gene networks were found in a comparison group of female and intersex crabs that involved heat shock proteins, ribosomes, and metabolism pathways; two core gene networks were found in the comparison group of male and intersex crabs that involved ribosomes and metabolism pathways. The six confirmed genes of Hsc70, Hsp90, Rpl18, Acsl1, Yip2, and Rpl7 had lower methylation levels in the promoter region of intersex crabs than that of female and male crabs. However, six genes showed higher expression in intersex crabs than in female and male crabs. Our results reveal that DNA methylation is involved in the formation and maintenance of life activities of intersex crabs through the regulation of gene expression, enriching the DNA methylation library of the whole genome of E. sinensis and providing new insights for a better understanding of the epigenetic regulation of the formation of intersex E. sinensis. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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Review

Jump to: Research

28 pages, 1927 KB

Open AccessReview

The Role of Papaverine in the Molecular and Biomechanical Mechanisms of Cervical Ripening: A Narrative Review

by Wojciech Flis, Mateusz Wartęga, Tomasz Góra and Maciej W. Socha

Int. J. Mol. Sci. 2026, 27(14), 6344; https://doi.org/10.3390/ijms27146344 - 17 Jul 2026

Viewed by 562

Abstract

Papaverine (PPV) has long been used in obstetric practice to facilitate cervical dilatation, yet its mechanism of action remains poorly understood. This creates an apparent paradox, as experimental studies indicate that PPV suppresses several inflammatory signaling pathways traditionally considered essential for physiological cervical [...] Read more.

Papaverine (PPV) has long been used in obstetric practice to facilitate cervical dilatation, yet its mechanism of action remains poorly understood. This creates an apparent paradox, as experimental studies indicate that PPV suppresses several inflammatory signaling pathways traditionally considered essential for physiological cervical ripening, despite its reported clinical benefits during labor. In this narrative review, we critically integrate current knowledge of cervical ripening biology with the pharmacological actions of PPV to reconcile this discrepancy. We propose that the reported clinical effects of PPV may be explained predominantly by modulation of cervical biomechanics rather than by direct enhancement of inflammatory remodeling. In particular, smooth muscle relaxation and cyclic nucleotide-dependent signaling may reduce functional cervical resistance and facilitate cervical dilatation despite the predominantly anti-inflammatory molecular profile of PPV. Although this mechanistic framework remains hypothetical, it provides a biologically plausible explanation for the apparent discrepancy between the molecular and clinical effects of papaverine and highlights priorities for future experimental and clinical research. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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14 pages, 2413 KB

Open AccessReview

Mitochondrial DNA Modification in Assisted Reproduction: Concept to Practice—A Narrative Review

by Mariam Mehwish Mohsin, Misbah Azher, Fatima Asghar, Hiba Habeebu Rahiman, Rajani Dube, Subhranshu Sekhar Kar, Shadha Nasser Mohammed Bahutair, Bellary Kuruba Manjunatha Goud and Swayam Siddha Kar

Int. J. Mol. Sci. 2026, 27(6), 2890; https://doi.org/10.3390/ijms27062890 - 23 Mar 2026

Viewed by 1228

Abstract

Mitochondria play a fundamental role in human reproduction by supplying the energy required for key early reproductive processes. As mitochondrial Deoxyribonucleic acid (mtDNA) is maternally inherited, pathogenic mutations can lead to multisystem disorders that are transmitted to offspring. Mitochondrial replacement therapy (MRT) has [...] Read more.

Mitochondria play a fundamental role in human reproduction by supplying the energy required for key early reproductive processes. As mitochondrial Deoxyribonucleic acid (mtDNA) is maternally inherited, pathogenic mutations can lead to multisystem disorders that are transmitted to offspring. Mitochondrial replacement therapy (MRT) has emerged as a promising assisted reproductive approach to prevent the transmission of pathogenic mtDNA by replacing defective mitochondria with healthy donor mitochondria. There have been recent reports of successful MRT in humans. However, MRT remains a relatively new procedure and needs further experiments to establish its long-term safety and effectiveness. Overall, mitochondrial replacement therapy holds significant promise in helping families build healthier futures. This review explores the evolution of mitochondrial DNA modification in reproductive cells and addresses the associated ethical considerations, including acceptable clinical indications, reproductive choices, and long-term considerations for affected children. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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32 pages, 419 KB

Open AccessReview

Peri-Transfer Glucocorticoid Therapy in Oocyte-Donation IVF Bridging the Immunological Gap

by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Charalampos Tsimpoukelis, Athanasios Karpouzos, Maria Anastasia Daskalaki, Nikolaos Kanakas, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis Show full author list Hide full author list

Int. J. Mol. Sci. 2026, 27(3), 1217; https://doi.org/10.3390/ijms27031217 - 26 Jan 2026

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Abstract

In vitro fertilisation via oocyte donation is a unique reproductive technique in which the embryo is fully separate from the receiver. This compels the immune system to exert more effort at the interface between the uterus and the remainder of the body. This [...] Read more.

In vitro fertilisation via oocyte donation is a unique reproductive technique in which the embryo is fully separate from the receiver. This compels the immune system to exert more effort at the interface between the uterus and the remainder of the body. This setting has maintained interest in peri-transfer glucocorticoid treatment as a possible approach to modify endometrial immunity and enhance implantation. Nevertheless, the data for this procedure are disjointed and mostly derive from investigations on autologous in vitro fertilisation. This narrative review consolidates contemporary evidence on endometrial immunology in oocyte donation cycles, analysing the mechanistic basis, clinical results, and constraints related to peri-implantation glucocorticoid therapy. Outcomes from randomised studies in autologous cycles consistently demonstrate that there is no advantage in live birth rates, but the claimed improvements in clinical pregnancy rates are from heterogeneous and low-quality data. Limited research exists on people who have received oocyte donations. The majority are diminutive and non-random, often integrating glucocorticoids with other therapies such as antibiotics, granulocyte colony-stimulating factor, or endometrial damage. These designs inhibit the dissociation of the independent impact of glucocorticoids. Recent comprehensive randomised studies on recurrent implantation failure further demonstrate the lack of advantages in live births and highlight possible safety issues. The current data do not support the usual use of peri-transfer glucocorticoids in oocyte donation for in vitro fertilisation; nevertheless, short-term, low-dose treatment may be justified in meticulously chosen immunological profiles. There is an urgent need for rigorously designed randomised studies focused only on oocyte-donation recipients to elucidate the therapeutic effectiveness, safety, and suitable clinical context for glucocorticoid treatment in this expanding patient demographic. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

30 pages, 711 KB

Open AccessReview

A Systematic Review on GLP-1 Receptor Agonists in Reproductive Health: Integrating IVF Data, Ovarian Physiology and Molecular Mechanisms

by Charalampos Voros, Fotios Chatzinikolaou, Ioannis Papapanagiotou, Spyridon Polykalas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Georgios Papadimas, Charalampos Tsimpoukelis, Dimitrios Vaitsis, Athanasios Karpouzos, Maria Anastasia Daskalaki, Nikolaos Kanakas, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis Show full author list Hide full author list

Int. J. Mol. Sci. 2026, 27(2), 759; https://doi.org/10.3390/ijms27020759 - 12 Jan 2026

Cited by 13 | Viewed by 6392

Abstract

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, [...] Read more.

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, and steroidogenic production, in addition to its systemic metabolic effects. Nonetheless, there is a limited comprehension of the molecular mechanisms that regulate these activities and their correlation with menstrual function, reproductive potential, and assisted reproduction. This comprehensive review focuses on ovarian biology, granulosa cell signaling networks, steroidogenesis, and translational fertility outcomes, integrating clinical, in vivo, and in vitro information to elucidate the effects of GLP-1 receptor agonists on reproductive health. We conducted a thorough search of PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating the effects of GLP-1RA on reproductive or ovarian outcomes, in accordance with PRISMA criteria. The retrieved data included metabolic changes, androgen levels, monthly regularity, ovarian structure, granulosa cell growth and death, FOXO1 signaling, FSH-cAMP-BMP pathway activity, and fertility or IVF results. Clinical trials shown that GLP-1 receptor agonists improve menstrual regularity, decrease body weight and central adiposity, increase sex hormone-binding globulin levels, and lower free testosterone in overweight and obese women with PCOS. Liraglutide, when combined with metformin, significantly improved IVF pregnancy rates, whereas exenatide increased natural conception rates. Mechanistic studies demonstrate that GLP-1R activation affects FOXO1 phosphorylation, hence promoting granulosa cell proliferation and anti-apoptotic processes. Incretin signaling altered steroidogenesis by reducing the levels of StAR, P450scc, and 3β-HSD, so inhibiting FSH-induced progesterone synthesis, while simultaneously enhancing BMP-Smad signaling. Animal studies demonstrated both beneficial (enhanced follicular growth, anti-apoptotic effects) and detrimental results (oxidative stress, granulosa cell death, uterine inflammation), indicating a context- and dose-dependent response. GLP-1 receptor agonists influence female reproductive biology by altering overall physiological processes and specifically impacting the ovaries via FOXO1 regulation, steroidogenic enzyme expression, and BMP-mediated FSH signaling. Preliminary clinical data indicate improved reproductive function in PCOS, as seen by increased pregnancy rates in both natural and IVF cycles; nevertheless, animal studies reveal a potential risk of ovarian and endometrial damage. These results highlight the need for controlled human research to clarify reproductive safety, molecular pathways, and optimum therapy timing, particularly in non-PCOS patients and IVF settings. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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61 pages, 2889 KB

Open AccessReview

Understanding the Secular Decline in Testosterone: Mechanisms, Consequences, and Clinical Perspectives

by Óscar Fraile-Martínez, Miguel A. Ortega and Cielo García-Montero

Int. J. Mol. Sci. 2026, 27(2), 692; https://doi.org/10.3390/ijms27020692 - 9 Jan 2026

Cited by 7 | Viewed by 28536

Abstract

Testosterone is a key regulator of male and female physiology, influencing reproductive function, muscle and bone anabolism, metabolic homeostasis, and psychological well-being. Growing evidence indicates a secular, age-independent decline in testosterone levels across populations, a trend associated with reduced fertility, metabolic and cardiovascular [...] Read more.

Testosterone is a key regulator of male and female physiology, influencing reproductive function, muscle and bone anabolism, metabolic homeostasis, and psychological well-being. Growing evidence indicates a secular, age-independent decline in testosterone levels across populations, a trend associated with reduced fertility, metabolic and cardiovascular dysfunction, mood disturbances, and impaired quality of life. While aging and genetic factors play a role, a wide range of modifiable influences—including obesity, physical inactivity, unhealthy dietary patterns, chronic stress, poor sleep, and exposure to endocrine-disrupting chemicals or other environmental stressors—appear to contribute substantially to this phenomenon. This narrative review synthesizes the evidence on testosterone’s physiological significance, the causes and consequences of its secular decline, and evaluates potential interventions, emphasizing lifestyle and environmental strategies (physical activity, nutrition, weight management, sleep, stress reduction, sunlight exposure) as well as pharmacological and nutraceutical options. Overall, the contemporary testosterone decline represents a complex, multifactorial public health issue requiring integrated approaches to preserve hormonal and systemic health. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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44 pages, 553 KB

Open AccessReview

Molecular Crosstalk Between Intrauterine hCG and Endometrial Receptivity: Signalling Pathways, Immune Modulation, and Translational Perspectives in IVF

by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Maria Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis

Int. J. Mol. Sci. 2026, 27(1), 278; https://doi.org/10.3390/ijms27010278 - 26 Dec 2025

Cited by 8 | Viewed by 2731

Abstract

A limited period of endometrial receptivity is defined by molecular interactions between the embryo and maternal tissues, which are crucial for successful implantation. The results of clinical studies assessing intrauterine human chorionic gonadotropin (hCG) as an endometrial priming agent in in vitro fertilisation [...] Read more.

A limited period of endometrial receptivity is defined by molecular interactions between the embryo and maternal tissues, which are crucial for successful implantation. The results of clinical studies assessing intrauterine human chorionic gonadotropin (hCG) as an endometrial priming agent in in vitro fertilisation (IVF) have been inconsistent, markedly affected by dose, timing, and cycle context. This narrative review summarises molecular data demonstrating that hCG modulates immunological, stromal, endothelial, and epithelial compartments in a coordinated manner, affecting essential endometrial processes. hCG promotes adhesion competence and proliferation in the epithelium via a microRNA-regulated signalling axis (miR-126-3p–PIK3R2–PI3K/Akt). Intrauterine hCG promotes controlled apposition and invasion at the vascular interface by selectively strengthening endothelial junctional cohesion via VE-cadherin and CD146, without promoting angiogenesis. hCG collaborates with ERK/mTOR signalling to regulate autophagy and apoptosis, alters steroid–receptor networks in the stroma, initiates early decidual and survival markers (ACTA2, NOTCH1, complement C3), and enhances stress resistance. hCG modifies the immunological milieu by enhancing the activity of regulatory T cells and altering the distribution of uterine natural killer cells. This facilitates immunological tolerance and the remodelling of spiral arteries. These pleiotropic effects together enhance biomarkers and provide a scientific justification for context-dependent clinical responses, including patient-chosen, directed methods for the delivery of intrauterine hCG during IVF. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

35 pages, 425 KB

Open AccessReview

Oxidative Stress–Telomere Axis in IVF: Molecular Mechanisms, Biomarkers, and Clinical Translation

by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Ioakeim Sapantzoglou, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Maria Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis

Int. J. Mol. Sci. 2025, 26(23), 11359; https://doi.org/10.3390/ijms262311359 - 24 Nov 2025

Cited by 10 | Viewed by 2259

Abstract

The reduction in oocyte competence and ovarian reserve coincides with reproductive ageing; nevertheless, the molecular mechanisms underlying this phenomenon remain poorly understood. Our testable mechanistic hypothesis is that the oxidative stress–telomere axis is a crucial regulatory mechanism controlling meiotic stability, mitochondrial resilience, and [...] Read more.

The reduction in oocyte competence and ovarian reserve coincides with reproductive ageing; nevertheless, the molecular mechanisms underlying this phenomenon remain poorly understood. Our testable mechanistic hypothesis is that the oxidative stress–telomere axis is a crucial regulatory mechanism controlling meiotic stability, mitochondrial resilience, and granulosa cell integrity. This notion posits that granulosa and cumulus cells have accelerated telomere attrition and impaired DNA-damage responses due to elevated amounts of reactive oxygen species, which also induce oxidative guanine lesions, inhibit telomerase function, and generate telomeric replication stress. This telomere-dependent vulnerability is anticipated to compromise developmental competence, disrupt meiotic spindle integrity, and diminish metabolic support to the oocyte, prior to observable declines in AMH or follicle count. Data from human IVF cohorts supports the model: Conditions such as PCOS, endometriosis, and POI have unique oxidative-telomeric profiles, whereas diminished telomere length in granulosa cells, reduced telomerase activity, and worse fertilisation, blastulation, and pregnancy outcomes are associated with increased follicular oxidative DNA damage. The findings suggest that oxidative DNA damage (8-OHdG), telomerase activity, and the structure of granulosa-cell telomeres may serve as preliminary indicators of preclinical ovarian ageing. This theory may be directly evaluated in forthcoming longitudinal studies and specific treatments related to telomerase regulation, mitochondrial medicines, or redox modulation. Consequently, the oxidative stress–telomere axis may represent a vital physiologic factor affecting reproductive lifespan and a prospective target for personalised ART techniques. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

17 pages, 578 KB

Open AccessReview

Tirzepatide as a Potential Disease-Modifying Therapy in Lipedema: A Narrative Review on Bridging Metabolism, Inflammation, and Fibrosis

by Diogo Pinto da Costa Viana, Adriana Luckow Invitti and Eduardo Schor

Int. J. Mol. Sci. 2025, 26(21), 10741; https://doi.org/10.3390/ijms262110741 - 5 Nov 2025

Cited by 12 | Viewed by 34573

Abstract

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular [...] Read more.

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide’s potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic–hormonal therapy capable of modifying the natural course of lipedema. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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42 pages, 633 KB

Open AccessReview

Impact of Bariatric Surgery on the Expression of Fertility-Related Genes in Obese Women: A Systematic Review of LEP, LEPR, MC4R, FTO, and POMC

by Charalampos Voros, Ioakeim Sapantzoglou, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Despoina Mavrogianni, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Georgios Papadimas, Ioannis Papapanagiotou, Dimitrios Vaitsis, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Vasileios Topalis, Marianna Theodora, Nikolaos Thomakos, Fotios Chatzinikolaou, Panagiotis Antsaklis, Dimitrios Loutradis, Evangelos Menenakos and Georgios Daskalakis Show full author list Hide full author list

Int. J. Mol. Sci. 2025, 26(21), 10333; https://doi.org/10.3390/ijms262110333 - 23 Oct 2025

Cited by 3 | Viewed by 3081

Abstract

Obesity is a multifaceted disorder influenced by various factors, with heredity being a significant contributor. Bariatric surgery is the most effective long-term intervention for morbid obesity and associated comorbidities, while outcomes vary significantly across individuals. Recent studies indicate that genetic and molecular determinants, [...] Read more.

Obesity is a multifaceted disorder influenced by various factors, with heredity being a significant contributor. Bariatric surgery is the most effective long-term intervention for morbid obesity and associated comorbidities, while outcomes vary significantly across individuals. Recent studies indicate that genetic and molecular determinants, particularly alterations in the leptin–melanocortin signalling pathway involving the fat mass and obesity-associated gene (FTO), pro-opiomelanocortin (POMC), melanocortin 4 receptor (MC4R), leptin (LEP), and leptin receptor (LEPR), influence the efficacy of weight loss and metabolic adaptations post-surgery. This narrative review consolidates evidence from peer-reviewed papers available in PubMed and Scopus until July 2025. The emphasis was on novel research and systematic reviews examining genetic polymorphisms, gene–environment interactions, and outcomes following bariatric procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). Recent research emphasised the integration of genetic screening and precision medicine models into clinical bariatric workflows. Variants in FTO (e.g., rs9939609), MC4R (e.g., rs17782313), LEPR, and POMC are associated with diminished weight loss post-surgery, an increased likelihood of weight regain, and reduced metabolic enhancement. Patients with bi-allelic mutations in MC4R, POMC, or LEPR exhibited poor long-term outcomes despite receiving effective physical interventions. Furthermore, genes regulating mitochondrial metabolism (such as PGC1A), adipokine signalling (such as ADIPOQ), and glucose regulation (such as GLP1R) have been demonstrated to influence the body’s response to sugar and the extent of weight gain or loss. Two recent systematic reviews elucidate that candidate gene investigations are beneficial; however, larger genome-wide association studies (GWAS) and machine learning techniques are necessary to enhance predictive accuracy. Integrating genetic and molecular screening with bariatric surgery planning possesses significant therapeutic potential. Genotyping can assist in patient selection, procedural decisions, and medication additions, particularly for those with variants that influence appetite regulation or metabolic flexibility. Advancements in precision medicine, including the integration of polygenic risk scores, omics-based profiling, and artificial intelligence, will enhance the customisation of surgical interventions and extend the lifespan of individuals with severe obesity. The epigenetic regulators of energy balance DNA methylation, histone changes, and microRNAs that may affect individual differences in weight-loss patterns after bariatric surgery are also briefly contextualised. We discuss the concept that epigenetic modulation of gene expression, mediated by microRNAs in response to food and exercise, may account for variations in metabolic outcomes post-surgery. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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22 pages, 3926 KB

Open AccessReview

Targeting Modifiable Risks: Molecular Mechanisms and Population Burden of Lifestyle Factors on Male Genitourinary Health

by Xingcheng Yang, Meiping Lan, Jiawen Yang, Yuyi Xia, Linxiang Han, Ling Zhang and Yu Fang

Int. J. Mol. Sci. 2025, 26(19), 9698; https://doi.org/10.3390/ijms26199698 - 5 Oct 2025

Cited by 2 | Viewed by 2834

Abstract

Health represents a state of complete physical, mental, and social well-being, with lifestyle factors accounting for approximately 60% of health determinants. Suboptimal health describes an intermediate condition between wellness and disease. According to 2023 WHO data, infertility affects approximately 17.5% of global adults, [...] Read more.

Health represents a state of complete physical, mental, and social well-being, with lifestyle factors accounting for approximately 60% of health determinants. Suboptimal health describes an intermediate condition between wellness and disease. According to 2023 WHO data, infertility affects approximately 17.5% of global adults, with male factors implicated in 30–50% of cases, establishing infertility as a critical public health challenge. Substantial preclinical and clinical evidence links suboptimal lifestyles to male reproductive dysfunction, positioning these behaviors as modifiable infertility risk factors encompassing environmental contaminants and lifestyle patterns. This systematic review synthesizes evidence on five key lifestyle determinants—tobacco, alcohol, microplastics, sedentariness, and sleep disruption—affecting male genitourinary health. Adopting an evidence-based medicine framework, we integrate epidemiological and experimental research to establish foundational knowledge for developing novel preventive strategies targeting male suboptimal health. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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23 pages, 627 KB

Open AccessReview

Time-Lapse Imaging in IVF: Bridging the Gap Between Promises and Clinical Realities

by Grzegorz Mrugacz, Igor Bołkun, Tomasz Magoń, Izabela Korowaj, Beata Golka, Tomasz Pluta, Olena Fedak, Paulina Cieśla, Joanna Zowczak and Ewelina Skórka

Int. J. Mol. Sci. 2025, 26(19), 9609; https://doi.org/10.3390/ijms26199609 - 1 Oct 2025

Cited by 10 | Viewed by 6628

Abstract

Time-lapse imaging (TLI) has emerged as a transformative technology in in vitro fertilization (IVF). This is because it offers continuous, non-invasive embryo assessment through morphokinetic profiling. It demonstrates key advantages such as reduced embryologist subjectivity, detection of dynamic anomalies, and improved implantation rates [...] Read more.

Time-lapse imaging (TLI) has emerged as a transformative technology in in vitro fertilization (IVF). This is because it offers continuous, non-invasive embryo assessment through morphokinetic profiling. It demonstrates key advantages such as reduced embryologist subjectivity, detection of dynamic anomalies, and improved implantation rates in niche populations. However, its clinical utility remains debated. Large trials and meta-analyses reveal no universal improvement in live birth rates compared to conventional methods. Key challenges underlying the outcome include algorithm generalizability, lab-specific protocol variability, and high costs. Nevertheless, TLI shows promise in specific contexts. For instance, Preimplantation Genetic Testing for Aneuploidies (PGT-A) cycles where it reduces unnecessary biopsies by predicting euploidy. However, even in this, its benefits are marginal in unselected populations. This review synthesizes evidence to highlight that TLI’s value is context-dependent, not universal. As such, adoption must be cautious to avoid resource misallocation without significant IVF outcome improvements. In future, personalized protocols, integration with non-invasive biomarkers, and multicenter collaboration are crucial to optimize TLI’s potential in assisted reproduction. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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20 pages, 899 KB

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Exploring Hirsutism: Epidemiology, Associated Endocrinal Abnormalities, and Societal Challenges in GCC—A Narrative Review

by Mohamed Anas Patni, Rajani Dube, Subhranshu Sekhar Kar, Biji Thomas George, Manjunatha Goud Bellary Kuruba, Suresh Kumar Srinivasamurthy and Abdalla Ahmed Eldaw Elamin

Int. J. Mol. Sci. 2025, 26(12), 5575; https://doi.org/10.3390/ijms26125575 - 11 Jun 2025

Cited by 4 | Viewed by 5912

Abstract

Hirsutism, characterized by excessive terminal hair growth in androgen-sensitive areas, presents significant medical and psychosocial challenges in Gulf Cooperation Council (GCC) countries. This narrative review explores the epidemiology, endocrine factors, molecular basis of pathophysiology, cultural influences, and management approaches to hirsutism within the [...] Read more.

Hirsutism, characterized by excessive terminal hair growth in androgen-sensitive areas, presents significant medical and psychosocial challenges in Gulf Cooperation Council (GCC) countries. This narrative review explores the epidemiology, endocrine factors, molecular basis of pathophysiology, cultural influences, and management approaches to hirsutism within the GCC. Regional factors such as consanguinity, rising obesity rates, and lifestyle habits contribute to a higher prevalence of hirsutism and related endocrine disorders, particularly polycystic ovary syndrome (PCOS). Cultural stigmas surrounding body hair further delay diagnosis and treatment, compounding psychological distress. The review examines the role of androgen excess, genetic susceptibility, and emerging molecular insights, including epigenetic dysregulations. Diagnostic limitations and the need for region-specific screening tools are discussed, alongside the current reliance on pharmacological, cosmetic, and traditional therapies. Public health initiatives targeting stigma reduction and early detection are emphasized. Future recommendations include culturally tailored research, enhanced public awareness, and the adoption of advanced diagnostic strategies to improve patient outcomes. This review aims to guide healthcare practices and inform policy development for the better management of hirsutism in the GCC context. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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