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18 pages, 4044 KiB  
Article
Preparation and Immunogenicity Evaluation of a Ferritin-Based GnRH Nanoparticle Vaccine
by Ying Xu, Weihao Zhao, Yuhan Zhu, Bo Sun, Congmei Wu and Yuhe Yin
Vaccines 2025, 13(8), 781; https://doi.org/10.3390/vaccines13080781 - 23 Jul 2025
Viewed by 313
Abstract
Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to [...] Read more.
Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article
(This article belongs to the Section Veterinary Vaccines)
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16 pages, 1455 KiB  
Article
A Genome-Wide Association Study of Anti-Müllerian Hormone (AMH) Levels in Samoan Women
by Zeynep Erdogan-Yildirim, Jenna C. Carlson, Mohanraj Krishnan, Jerry Z. Zhang, Geralyn Lambert-Messerlian, Take Naseri, Satupaitea Viali, Nicola L. Hawley, Stephen T. McGarvey, Daniel E. Weeks and Ryan L. Minster
Genes 2025, 16(7), 793; https://doi.org/10.3390/genes16070793 - 30 Jun 2025
Viewed by 425
Abstract
Background/Objectives: The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused [...] Read more.
Background/Objectives: The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused exclusively on women of European ancestry, limiting insights into diverse populations. Methods: We conducted a GWAS to identify genetic loci associated with circulating AMH levels in a sample of 1185 Samoan women from two independently recruited samples. Using a Cox mixed-effects model we accounted for AMH levels below detectable limits and meta-analysed the summary statistics using a fixed-effect model. To prioritize variants and genes, we used FUMA and performed colocalization and transcriptome-wide association analysis (TWAS). We also assessed whether any previously reported loci were replicated in our GWAS. Results: We identified eleven genome-wide suggestive loci, with the strongest signal at ARID3A (19-946163-G-C; p = 2.32 × 10−7) and replicated rs10093345 near EIF4EBP1. The gene-based testing revealed ARID3A and R3HDM4 as significant genes. Integrating GWAS results with expression quantitative trait loci via TWAS, we detected seven transcriptome-wide significant genes. The lead variant in ARID3A is in high linkage disequilibrium (r2 = 0.79) with the known age-at-menopause variant 19-950694-G-A. Nearby KISS1R is a biologically plausible candidate gene that encodes the kisspeptin receptor, a regulator of ovarian follicle development linked to AMH levels. Conclusions: This study expands our understandings of AMH genetics by focusing on Samoan women. While these findings may be particularly relevant to Pacific Islanders, they hold broader implications for reproductive phenotypes such as the ovarian reserve, menopause timing, and polycystic ovary syndrome. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 2177 KiB  
Article
Yamabushitake Mushroom (Hericium erinaceus (Bull.) Pers. 1797) Mycelium Improves Reproductive System Dysfunction in Male Rats Induced by Polystyrene Microplastics
by Yi-Yuh Hwang, Sabri Sudirman, En-Yu Wei, Ruei-Feng Shiu, Zwe-Ling Kong and Deng-Fwu Hwang
Int. J. Mol. Sci. 2025, 26(12), 5735; https://doi.org/10.3390/ijms26125735 - 15 Jun 2025
Viewed by 684
Abstract
The use of plastic products has increased, leading to higher levels of plastic pollution, and it is becoming a major public health concern. Health risks—especially those related to reproductive system dysfunction caused by polystyrene microplastics (PS-MPs)—are emerging issues that require urgent attention. This [...] Read more.
The use of plastic products has increased, leading to higher levels of plastic pollution, and it is becoming a major public health concern. Health risks—especially those related to reproductive system dysfunction caused by polystyrene microplastics (PS-MPs)—are emerging issues that require urgent attention. This study aimed to investigate the effects of erinacine A-enriched Hericium erinaceus mycelium (HE) on high-fat-diet- and PS-MP-induced reproductive system dysfunction in male rats. Reproductive dysfunction was induced by administering a high-fat diet followed by exposure to PS-MPs for six weeks. The results showed that HE treatment significantly reduced nitric oxide levels and enhanced glutathione peroxidase activity. Furthermore, HE supplementation significantly downregulated pro-inflammatory cytokines such as interleukin (IL)-6 and IL-1β. Additionally, HE treatment significantly increased Kiss1 concentration, upregulated follicle-stimulating hormone and testosterone levels, reduced the area of the seminiferous tubule lumen, and prevented a reduction in epithelial thickness. HE treatment also significantly increased sperm count and reduced sperm abnormalities. Based on these findings, HE supplementation helps prevent reproductive system dysfunction by reducing oxidative stress and pro-inflammatory cytokines. Therefore, erinacine A-enriched H. erinaceus mycelium could be considered a potential food supplement or functional food ingredient for the treatment of reproductive or testicular dysfunction. Full article
(This article belongs to the Section Molecular Pharmacology)
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11 pages, 193 KiB  
Article
Exploring the Potential Impact of SERPINE Gene Expression in Cumulus Cells During Fertility Treatments: A Single Center Study
by Sofoklis Stavros, Anastasios Potiris, Despoina Mavrogianni, Efthalia Moustakli, Kyriaki Tsiorou, Athanasios Zikopoulos, Nikolaos Kathopoulis, Charalampos Theofanakis, Dimitrios Loutradis, Ekaterini Domali and Peter Drakakis
Clin. Pract. 2025, 15(5), 83; https://doi.org/10.3390/clinpract15050083 - 23 Apr 2025
Viewed by 408
Abstract
Background/Objectives: Cumulus cells have been proposed to be indicators of oocyte quality. In this study, oocyte cumulus cells were analyzed for SERPINE gene expression. High SERPINE gene expression in cumulus cells is associated with reduced oocyte maturity. However, high mRNA levels in [...] Read more.
Background/Objectives: Cumulus cells have been proposed to be indicators of oocyte quality. In this study, oocyte cumulus cells were analyzed for SERPINE gene expression. High SERPINE gene expression in cumulus cells is associated with reduced oocyte maturity. However, high mRNA levels in granulosa cells are associated with follicles that result in pregnancy. This study aimed to evaluate SERPINE gene expression in cumulus cells across different ovarian stimulation protocols and its potential impact on follicle number, oocyte maturity, and embryo quality. Methods: The sample of the study consisted of 93 infertile women that underwent a five-day fixed antagonist protocol. Detection of SERPINE gene expression levels in cumulus cells was performed by extracting and isolating the total RNA produced in granulosa cells, and conducting cDNA synthesis and Real-Time Polymerase Chain Reaction. Results: The SERPINE gene expression in CCs was assessed in 71 samples. The SERPINE gene expression levels in CCs were categorized based on the ΔCp values. Most participants (65.9%) exhibited a high expression of the SERPINE gene, with ΔCp values greater than 2. Higher gene expression resulted in a higher number of follicles. However, no statistically significant results were observed regarding the number of follicles and the number of embryos. Conclusions: The study results provide insights into the expression patterns of the SERPINE gene in CCs and underscore the complexity of fertility-related biomarkers and the need for further investigation. SERPINE expression appears to be associated with follicle count, while its role in predicting oocyte quality and pregnancy success remains inconclusive. Full article
12 pages, 1503 KiB  
Article
The Anti-Acne and Reduction of Hyperpigmentation Effects of Products Containing Retinol, Niacinamide, Ceramides, and Dipotassium Glycyrrhizinate in Chinese Women
by Zheng Kuai, Wenna Wang, Jiahong Yang, Xiaofeng He, Yi Yi, Hequn Wang, Yijie Zheng and Yunfei Ai
Cosmetics 2025, 12(2), 69; https://doi.org/10.3390/cosmetics12020069 - 8 Apr 2025
Cited by 1 | Viewed by 3901
Abstract
Acne vulgaris is a dermatological condition characterized by the hyperkeratinization of sebaceous follicles, which can further lead to post-inflammatory hyperpigmentation. Considering the intricate pathophysiology of acne, it is essential to develop novel topical therapies that are capable of targeting multiple underlying mechanisms of [...] Read more.
Acne vulgaris is a dermatological condition characterized by the hyperkeratinization of sebaceous follicles, which can further lead to post-inflammatory hyperpigmentation. Considering the intricate pathophysiology of acne, it is essential to develop novel topical therapies that are capable of targeting multiple underlying mechanisms of acne. The objective of this study was to study the effect of products containing retinol, niacinamide, ceramides, and dipotassium glycyrriszinate on acne-related markers. A total of 43 women with acne skin (including sensitive skin) were enrolled. To evaluate the effect of test products on acne-related indicators following 4 weeks of use, this study combined clinical assessments of skin condition (acne lesion counts), instrumental assessments (skin gloss), and photo tracking using VISIA-CR and Primos CR systems, which encompass metrics such as a*, ITA°, skin area (%) covered by sebum spots, and the presence of sebum spots. Adverse reactions were also assessed. After 4 weeks of treatment, significant reductions were observed in both the inflammatory acne lesion count and non-inflammatory acne lesion count, while there was also a significant decrease in skin redness a* and skin area (%) covered by sebum spots and a significant increase in skin brightness ITA° and gloss. No adverse events occurred during the entire testing process. In summary, the daily application of products containing retinol, niacinamide, and ceramides not only improves acne-related symptoms but also alleviates post-inflammatory hyperpigmentation caused by acne, which suggests that such products have the potential to meet the dual needs of brightening and acne care. Full article
(This article belongs to the Section Cosmetic Dermatology)
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16 pages, 6378 KiB  
Article
Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve
by Enes Karaman, Adem Yavuz, Erol Karakas, Esra Balcioglu, Busra Karaca, Hande Nur Doganay, Koray Gorkem Sacinti and Orhan Yildiz
Vaccines 2025, 13(4), 345; https://doi.org/10.3390/vaccines13040345 - 24 Mar 2025
Cited by 1 | Viewed by 52573
Abstract
Objectives: This study aimed to elucidate the effects of messenger RNA (mRNA) and inactivated coronavirus disease 2019 (COVID-19) vaccines on ovarian histology and reserve in rats. Methods: Thirty female Wistar albino rats, aged 16–24 weeks, were randomly divided into three groups [...] Read more.
Objectives: This study aimed to elucidate the effects of messenger RNA (mRNA) and inactivated coronavirus disease 2019 (COVID-19) vaccines on ovarian histology and reserve in rats. Methods: Thirty female Wistar albino rats, aged 16–24 weeks, were randomly divided into three groups (n = 10): control, mRNA vaccine, and inactivated vaccine groups. Each vaccine group received two doses (on day 0 and day 28) at human-equivalent doses. Four weeks post-second vaccination, ovarian tissues were harvested for analysis. Results: Immunohistochemical analysis was performed to evaluate the expression of transforming growth factor beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), caspase-3, and anti-Müllerian hormone (AMH) in ovarian follicles. Both vaccines induced significant increases in TGF-β1, VEGF, and caspase-3 expression, with more pronounced effects in the mRNA vaccine group. Conversely, AMH expression in the granulosa cells of primary, secondary, and antral follicles showed marked reductions (p < 0.001). The counts of primordial, primary, and secondary follicles decreased significantly in the inactivated vaccine group relative to controls and further in the mRNA vaccine group compared to the inactivated group (p < 0.001). Additionally, the mRNA vaccine group exhibited a decrease in antral and preovulatory follicles and an increase in atretic follicles compared to the other groups (p < 0.05). The serum AMH level was diminished with the mRNA vaccination in comparison with the control and inactivated groups. Conclusions: Our findings suggest that both mRNA and inactivated COVID-19 vaccines may detrimentally impact ovarian reserve in rats, primarily through accelerated follicular loss and alterations in apoptotic pathways during folliculogenesis. Given these observations in a rat model, further investigations into the vaccines’ effects on human ovarian reserve are needed. Full article
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21 pages, 2536 KiB  
Article
Impact of PM2.5 Exposure from Wood Combustion on Reproductive Health: Implications for Fertility, Ovarian Function, and Fetal Development
by Paulo Salinas, Nikol Ponce, Mariano del Sol and Bélgica Vásquez
Toxics 2025, 13(4), 238; https://doi.org/10.3390/toxics13040238 - 24 Mar 2025
Cited by 1 | Viewed by 908
Abstract
This study evaluates the impact of PM2.5 exposure from wood combustion on reproductive health and fetal development using an experimental model in Sprague Dawley rats. The study was conducted in Temuco, Chile, where high levels of air pollution are primarily attributed to residential [...] Read more.
This study evaluates the impact of PM2.5 exposure from wood combustion on reproductive health and fetal development using an experimental model in Sprague Dawley rats. The study was conducted in Temuco, Chile, where high levels of air pollution are primarily attributed to residential wood burning. A multigenerational exposure model was implemented using controlled exposure chambers with filtered (FA) and unfiltered (NFA) air. Second-generation (G2) female rats (n = 48) were exposed pregestationally (60 days) and gestationally (23 days) under four conditions: FA/FA, FA/NFA, NFA/FA, and NFA/NFA. PM2.5 concentration and composition were monitored using beta-ray attenuation and X-ray fluorescence spectrometry. Reproductive parameters, ovarian follicle counts, and hormonal levels were assessed via vaginal cytology, histological analysis, and chemiluminescence immunoassays. PM2.5 exposure disrupted estrous cyclicity (p = 0.0001), reduced antral and growing follicles (p = 0.0020; p = 0.0317), and increased post-implantation losses (p = 0.0149). Serum progesterone and estradiol levels were significantly altered (p < 0.05). Despite ovarian disruptions, fertility rates remained unchanged. These findings suggest that chronic exposure to wood smoke-derived PM2.5 adversely affects ovarian function and fetal growth without significantly impairing overall reproductive capacity. This study highlights the need for public health policies to mitigate wood smoke pollution. Full article
(This article belongs to the Topic Biomass Use and its Health and Environmental Effects)
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15 pages, 1658 KiB  
Article
Association of Polycystic Ovary Syndrome with Clinical, Physical, and Reproductive Factors: A Data-Driven Analysis
by Ismat Ara Begum, A. S. M. Sanwar Hosen, Deepak Ghimire and Mi Jin Park
Diagnostics 2025, 15(6), 711; https://doi.org/10.3390/diagnostics15060711 - 12 Mar 2025
Cited by 1 | Viewed by 1543
Abstract
Background/Objectives: Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine disorder with significant clinical and reproductive implications. Identifying dose–response relationships between clinical, physical, and reproductive factors and PCOS can enhance diagnostic accuracy and inform treatment strategies. This study utilized a data-driven approach to [...] Read more.
Background/Objectives: Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine disorder with significant clinical and reproductive implications. Identifying dose–response relationships between clinical, physical, and reproductive factors and PCOS can enhance diagnostic accuracy and inform treatment strategies. This study utilized a data-driven approach to analyze the associations between key factors, including age, weight, menstrual cycle length, Anti-Mullerian Hormone (AMH) levels, and follicle count, with PCOS prevalence. Methods: A retrospective analysis was conducted on a dataset of 539 participants to determine the optimal ranges of these factors associated with an increased likelihood of PCOS diagnosis. Statistical analyses were conducted using Python, including correlation matrix, univariate and multivariate logistic regression, and dose–response evaluations. Results: Our findings demonstrated that the risk of PCOS increases positively in women under 32 years of age. AMH levels above 4.18 ng/mL were strongly associated with PCOS, suggesting that higher AMH levels may reflect excessive follicular activity rather than enhanced ovarian function. Weight was positively correlated with PCOS, emphasizing the role of metabolic disturbances in its pathophysiology. Additionally, menstrual cycle length exhibited a non-linear association with PCOS, with both shortened and prolonged cycles being indicative of hormonal dysregulation. A higher follicle count was consistently linked to PCOS, reinforcing its diagnostic significance. Conclusions: This study provides evidence of non-linear dose–response relationships between PCOS and clinical, physical, and reproductive factors. The proposed optimal ranges may serve as valuable reference points for clinicians, aiding in early diagnosis and personalized management strategies for women with PCOS. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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23 pages, 3754 KiB  
Article
Depletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice
by Monica Moore, Busra Cetinkaya-Un, Papri Sarkar, Umit A. Kayisli, Nihan Semerci-Gunay, Michael Teng, Charles J. Lockwood and Ozlem Guzeloglu-Kayisli
Int. J. Mol. Sci. 2025, 26(6), 2471; https://doi.org/10.3390/ijms26062471 - 10 Mar 2025
Viewed by 902
Abstract
Prenatal stress (PNS) impairs offspring ovarian development by exerting negative long-term effects on postnatal ovarian function and folliculogenesis. FKBP51 is a stress-responsive protein that inhibits glucocorticoid and progesterone receptors. We hypothesize that FKBP51 contributes to impaired ovarian development and folliculogenesis induced by PNS. [...] Read more.
Prenatal stress (PNS) impairs offspring ovarian development by exerting negative long-term effects on postnatal ovarian function and folliculogenesis. FKBP51 is a stress-responsive protein that inhibits glucocorticoid and progesterone receptors. We hypothesize that FKBP51 contributes to impaired ovarian development and folliculogenesis induced by PNS. Timed-pregnant Fkbp5+/+ (wild-type) and Fkbp5−/− (knockout) mice were randomly assigned to either the undisturbed (nonstress) or PNS group, with exposure to maternal restraint stress from embryonic days 8 to 18. Ovaries from the offspring were harvested and stained, and follicles were counted according to their stages. Ovarian expressions of FKBP51 were evaluated by immunohistochemistry and Fkbp5 and steroidogenic enzymes were evaluated by qPCR. Compared to controls, Fkbp5+/+ PNS offspring had increased peripubertal primordial follicle atresia and fewer total follicles in the adult and middle-aged groups. In adult Fkbp5+/+ offspring, PNS elevated FKBP51 levels in granulosa cells of primary to tertiary follicles. Our results suggest that PNS administration increased FKBP51 levels, depleted the ovarian reserve, and dysregulated ovarian steroid synthesis. However, these PNS effects were tolerated in Fkbp5−/− mice, supporting the conclusion that FKBP51 contributes to reduced ovarian reserve induced by PNS. Full article
(This article belongs to the Section Molecular Biology)
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13 pages, 273 KiB  
Review
Platelet-Rich Plasma and Electrochemical Biosensors: A Novel Approach to Ovarian Function Evaluation and Diagnostics
by Tatjana Ivaskiene, Greta Kaspute, Egle Bareikiene and Urte Prentice
Int. J. Mol. Sci. 2025, 26(5), 2317; https://doi.org/10.3390/ijms26052317 - 5 Mar 2025
Cited by 1 | Viewed by 1186
Abstract
Preserving ovarian function is important to women’s reproductive health. It is necessary for fertility and maintaining the overall hormonal balance. Platelet-rich plasma (PRP) is an autologous plasma containing a predominately platelet concentrate prepared from fresh blood. It has been observed that PRP injections [...] Read more.
Preserving ovarian function is important to women’s reproductive health. It is necessary for fertility and maintaining the overall hormonal balance. Platelet-rich plasma (PRP) is an autologous plasma containing a predominately platelet concentrate prepared from fresh blood. It has been observed that PRP injections into the ovary can renew the functional cells of the cortical layer of the ovary follicles and reactivate the production of sex hormones. It may improve a woman’s fertility in the case of premature ovarian failure, the condition after chemotherapy treatment, or during the climacteric period. The main markers to evaluate the procedure’s success are elevated anti-Müllerin hormone and enlarged count level of atrial follicles in ovaries. The aim of this review is to identify the ovarian PRP procedure success markers and point out the electrochemical sensor techniques. Literature was selected depending on including and excluding criteria; studies were sorted by topics in two blocks: PRP biomarkers and electrochemistry. As PRP acts as a regenerative care, electrochemical biosensors can provide accurate, real-time data to evaluate the biological response to PRP therapy. The biosensors’ ability to monitor hormonal levels and follicle development serves as objective markers of the effectiveness of PRP in restoring ovarian function. Together, these approaches enable a more precise evaluation of ovarian health and fertility outcomes after PRP intervention. Full article
(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)
11 pages, 2260 KiB  
Article
Technical and Performance Characteristics Between Different Anti-Mullerian Hormone (AMH) Assay Methods and Antral Follicle Count (AFC) in Malaysian Women with Infertility: A University-Based Centre Cohort
by Chong Jie Wen, Mohd Faizal Ahmad, Muhammad Azrai Abu, Nalisa Shamyra Johari, Izzatul Aliaa Badaruddin, Shah Shamsul Azhar and Abdul Kadir Abdul Karim
Life 2025, 15(3), 383; https://doi.org/10.3390/life15030383 - 28 Feb 2025
Viewed by 1068
Abstract
Backgrounds: Evaluating the AMH level and AFC are crucial in infertility practice. Thus, accurate measurement is paramount. Various methods are available and selecting the right process is essential to ensure good reproducibility and precise results. Thus, our study aims to determine the analytical [...] Read more.
Backgrounds: Evaluating the AMH level and AFC are crucial in infertility practice. Thus, accurate measurement is paramount. Various methods are available and selecting the right process is essential to ensure good reproducibility and precise results. Thus, our study aims to determine the analytical performance of AMH Plus and AFIAS-AMH and the correlation between the two AMH assays and AFC values. Methods: A prospective study was conducted at the Advanced Reproductive Center, Hospital Canselor Tuanku Mukhriz (HCTM), Faculty of Medicine, National University of Malaysia, to compare the correlation between the AMH assay methods and AFCs. It included 100 patients from Feb 2024 until June 2024. Results: A total of 100 women with infertility, with a mean age of 35.87 ± 3.92, were included in our study. Our results revealed a strong positive correlation between the two AMH assays, with the comparable performance of AMH Plus and AFIAS-AMH. We also found that the serum AMH evaluation was comparable with the routine AFC assessment. Conclusions: Our findings indicated that serum AMH levels determine the association between AMH levels and follicle counts and the correlation between AMH concentrations and assays. Our study demonstrated the competent repeatability, acceptable linearity, and laboratory precision of the AFIAS-AMH test and comparative assessment of the AFC and serum AMH evaluation. Full article
(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)
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15 pages, 492 KiB  
Systematic Review
Unveiling the Impact of COVID-19 on Ovarian Function and Premature Ovarian Insufficiency: A Systematic Review
by Charalampos Voros, Despoina Mavrogianni, Aspasia Minaoglou, Anthi-Maria Papahliou, Vasileios Topalis, Antonia Varthaliti, Dimitris Mathiopoulos, Panagiota Kondili, Menelaos Darlas, Agni Pantou, Sophia Sina, Antonia Athanasiou, Diamantis Athanasiou, Dimitrios Loutradis and Georgios Daskalakis
Biomedicines 2025, 13(2), 407; https://doi.org/10.3390/biomedicines13020407 - 7 Feb 2025
Cited by 2 | Viewed by 3277
Abstract
Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which [...] Read more.
Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which are enhanced by its entrance into ovarian tissues via ACE2 receptors. The purpose of this comprehensive review was to investigate the molecular pathways that link SARS-CoV-2 infection to POI and analyze their consequences for ovarian reserve and fertility. Methods: We searched databases such as PubMed, Scopus, EMBASE, and Google Scholar for papers published between 2020 and 2024. Eligible studies investigated the effects of SARS-CoV-2 on ovarian function, including the hormonal indicators anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH), oocyte quality, and ovarian reserve. The data were compiled into a complete examination of molecules and clinical findings. Increased inflammatory indicators, such as interleukin-6 and NLRP3 inflammasome activation, impaired ovarian homeostasis. Anti-SARS-CoV-2 antibodies in follicular fluid could have impaired oocyte quality. Observational studies showed transitory decreases in AMH and changed FSH levels following infection, with variable effects on antral follicle count and IVF results. Changes in lipid profiles and VEGF expression emphasized the virus’s influence on ovarian angiogenesis and the ovarian microenvironment. Conclusions: SARS-CoV-2 infection impairs ovarian function by causing oxidative stress, inflammation, and hormonal disruption, thereby increasing the incidence of POI. While most alterations are temporary, the long-term reproductive consequences remain unknown. Continuous monitoring and specific treatments are required to reduce the reproductive risks associated with COVID-19. Full article
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16 pages, 16488 KiB  
Article
Peritoneal Endometriosis Impairs Ovarian Reserve and Increases Atresia in a Rat Model
by Analía Ricci, Tatiana Bengochea, Carla Olivares, Sofía del Valle, Julieta Simone, Kristina Gemzell-Danielsson, Rosa Inés Barañao, Gabriela Meresman and Mariela Bilotas
Biomedicines 2025, 13(2), 348; https://doi.org/10.3390/biomedicines13020348 - 3 Feb 2025
Cited by 2 | Viewed by 1168
Abstract
Background/Objectives: Endometriosis has a marked impact on fertility, although the mechanisms behind this relationship remain poorly understood, particularly in cases without significant anatomical distortions or in the context of ovarian endometriomas. This study aimed to investigate the effect of peritoneal endometriosis on ovarian [...] Read more.
Background/Objectives: Endometriosis has a marked impact on fertility, although the mechanisms behind this relationship remain poorly understood, particularly in cases without significant anatomical distortions or in the context of ovarian endometriomas. This study aimed to investigate the effect of peritoneal endometriosis on ovarian function by assessing ovarian reserve and apoptosis. Methods: Peritoneal endometriosis was surgically induced in Sprague Dawley rats through the autotransplantation of uterine fragments onto the bowel mesothelium. One month post-surgery, ovarian structures were counted, follicle and corpora lutea apoptosis was evaluated by TUNEL, and apoptotic-related protein expression in ovaries was assessed by Western blot. Additionally, a co-culture system using 12Z endometriotic and KGN granulosa cell lines was utilized to evaluate gene expression by RT-qPCR. Results: Rats with peritoneal endometriosis exhibited a significant reduction in ovarian structures characterized by a low number of total follicles, particularly primordial, primary, preantral, and late-antral follicles. Consistently, AMH protein expression was decreased in ovaries in the presence of endometriosis. In addition, this disease led to a significant increase in late-antral follicles that were TUNEL-positive and in the number of apoptotic cells in corpora lutea, indicating higher apoptosis in endometriosis ovaries. Concomitantly, the altered expression of apoptosis-related proteins was observed, with increased procaspase 3 and decreased BCL-2 expression. In addition, KGN granulosa cells co-cultured with 12Z endometriotic cells displayed reduced KITLG mRNA expression and increased AMHR2 mRNA expression. Conclusions: Peritoneal endometriosis significantly impairs ovarian health by disrupting folliculogenesis, reducing ovarian reserve, and increasing apoptosis, potentially accelerating ovarian aging and contributing to infertility. These results underscore the need for further research to identify the molecular pathways involved and to develop targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Molecular and Clinical Aspects of Endometriosis Pathophysiology)
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16 pages, 1241 KiB  
Article
Antioxidant Intake and Ovarian Reserve in Women Attending a Fertility Center
by Ana B. Maldonado-Cárceles, Irene Souter, Ming-Chieh Li, Makiko Mitsunami, Irene Dimitriadis, Jennifer B. Ford, Lidia Mínguez-Alarcón and Jorge E. Chavarro
Nutrients 2025, 17(3), 554; https://doi.org/10.3390/nu17030554 - 31 Jan 2025
Viewed by 2763
Abstract
Background/Objectives: The aim of this study was to investigate the association between antioxidant intake and antral follicle count (AFC), a marker of ovarian reserve, in women attending a fertility clinic. Methods: We conducted an observational study with 567 women undergoing infertility evaluation at [...] Read more.
Background/Objectives: The aim of this study was to investigate the association between antioxidant intake and antral follicle count (AFC), a marker of ovarian reserve, in women attending a fertility clinic. Methods: We conducted an observational study with 567 women undergoing infertility evaluation at the Massachusetts General Hospital Fertility Center, who were enrolled in the Environment and Reproductive Health (EARTH) study. Participants filled out the lifestyle and health questionnaires and a validated food frequency questionnaire (FFQ) for assessing habitual dietary intake and underwent a transvaginal ultrasound to measure AFC. Intake of nutrients with direct antioxidant capacity (vitamin A, C, and E and carotenoids) and intake of antioxidant food sources were estimated from the FFQ. Adjusted Poisson regression models were fitted to assess the relationships between antioxidants and AFC while adjusting for potential confounders. Non-linearity was assessed with restricted cubic splines. Results: The median (interquartile range) age and AFC of participants were 35.0 (32.0–38.0) years and 13 (9–18), respectively. Our findings revealed a non-linear association between lycopene intake and AFC. There was a positive linear association with the highest AFC among women consuming approximately 6000 mcg/day of lycopene (p for non-linearity = 0.003). An inverse association was observed between retinol intake, predominantly from dairy foods, and AFC among women aged under 35 years (p-trend < 0.001 and 0.01, respectively). Conclusions: Our findings suggest that lycopene intake might influence the ovarian reserve in fertility patients. The observed inverse association with retinol, if confirmed, may reflect biological mechanisms different from oxidative stress. The underlying mechanisms of these associations remain to be elucidated and warrant further investigation. Full article
(This article belongs to the Special Issue Impact of Diet, Nutrition and Lifestyle on Reproductive Health)
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Article
Association of Glycemic Index, Glycemic Load, and Carbohydrate Intake with Antral Follicle Counts Among Subfertile Females
by Makiko Mitsunami, Maryam Kazemi, Amy R. Nichols, Lidia Mínguez-Alarcón, Victoria W. Fitz, Irene Souter, Russ Hauser and Jorge E. Chavarro
Nutrients 2025, 17(3), 382; https://doi.org/10.3390/nu17030382 - 21 Jan 2025
Cited by 1 | Viewed by 1309
Abstract
Background/Objectives: Few studies have investigated the association of dietary glycemic index (GI), glycemic load (GL), and carbohydrate intake with antral follicle count (AFC). This study aimed to investigate the association of total carbohydrate intake and carbohydrate quality, measured by dietary GI and GL, [...] Read more.
Background/Objectives: Few studies have investigated the association of dietary glycemic index (GI), glycemic load (GL), and carbohydrate intake with antral follicle count (AFC). This study aimed to investigate the association of total carbohydrate intake and carbohydrate quality, measured by dietary GI and GL, with ovarian reserve assessed by AFC. Methods: This study included 653 females from the Environment And Reproductive Health Study who completed AFC and food frequency questionnaire. Of these, 579 female individuals had a quantifiable AFC in both ovaries and were included in the primary analysis. We estimated average GI and GL for each participant from self-reported intakes of carbohydrate-containing foods and divided participants into tertiles. Poisson regression models were used to quantify the relations of GI, GL, carbohydrates, and AFC while adjusting for potential confounders. Results: Participants had a median age of 35 y. Compared to participants in the lowest tertile of dietary GI, those in the highest tertile had a 6.3% (0.6%, 12.3%) higher AFC (p, trend 0.03) after adjustment for potential confounders. Stratified analyses revealed that the association between GI and AFC was present only among participants who had not undergone infertility evaluations. Conclusions: A higher dietary GI was associated with a higher AFC. Subgroup analyses among individuals who had not had a diagnostic evaluation of infertility before joining the study suggest that high-glycemic carbohydrates may be related to PCOM. Full article
(This article belongs to the Special Issue Impact of Diet, Nutrition and Lifestyle on Reproductive Health)
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