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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 6094

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Special Issue Editor

Dr. Kamil Gill

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Guest Editor

Department of Histology and Developmental Biology, Faculty of Health Sciences, Pomeranian Medical University, 71-210 Szczecin, Poland
Interests: male fertility; semen analysis; sperm chromatin; sperm DNA fragmentation; oxidative stress; reactive oxygen species
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Special Issue Information

Dear Colleagues,

We are pleased to announce this Special Issue, which will highlight the latest research in reproductive physiology and endocrinology. The foundation of modern therapy lies in a deep understanding of the biological processes occurring in the reproductive system under physiological and pathological conditions. Although these studies are called basic science, they use advanced molecular methods to explore changes at the genetic and epigenetic level, as well as the influence of environmental factors on these changes.

In addition, the study of reproductive endocrinology cannot be ignored; reproductive endocrine disorders can occur due to abnormal changes in any part of the hypothalamic–pituitary–gonadal axis, and can include a variety of symptoms, including infertility, hirsutism, virilization, oligomenorrhea and amenorrhea in women and infertility and changes in sexual function in men. In particular, understanding the role of hormones and their regulatory mechanisms in infertility is vital. We will focus on the effects of obesity, hypothyroidism, polycystic ovary syndrome, reproductive hormones, and IVF on reproductive health.

This Special Issue aims to provide a comprehensive overview of recent advances in reproductive physiology and reproductive endocrinology to help us better understand the functioning of the reproductive system and reveal the processes leading to its dysfunction. We encourage the submission of original research articles and reviews, especially those that provide results at the molecular level.

Dr. Kamil Gill
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

reproductive
endocrinology
reproductive hormones
embryology
molecular research
IVF
obesity

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Published Papers (7 papers)

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Research

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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

Viewed by 690

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 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

Viewed by 301

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 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

Viewed by 415

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 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

Viewed by 359

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 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 1 | Viewed by 1755

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 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

Viewed by 708

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, 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

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20 pages, 899 KB

Open AccessReview

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

Viewed by 1101

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 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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