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Galaxamide Ameliorates Cisplatin-induced Uterine Injury via Anti‑inflammatory and Antiapoptotic Mechanisms in Mice. Galaxamide通过抗炎和抗凋亡机制改善小鼠顺铂诱导的子宫损伤。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-08 DOI: 10.1007/s43032-026-02186-5
Zihao Peng, Bo Yao, Ziyi Ling, Xingwei Zhang, Zehuan Chen, Shihai Xu, Hanlin Shuai, Bihui Guo, Ping Li
{"title":"Galaxamide Ameliorates Cisplatin-induced Uterine Injury via Anti‑inflammatory and Antiapoptotic Mechanisms in Mice.","authors":"Zihao Peng, Bo Yao, Ziyi Ling, Xingwei Zhang, Zehuan Chen, Shihai Xu, Hanlin Shuai, Bihui Guo, Ping Li","doi":"10.1007/s43032-026-02186-5","DOIUrl":"https://doi.org/10.1007/s43032-026-02186-5","url":null,"abstract":"<p><p>Cisplatin treatment can cause ovarian dysfunction, but its impact on uterine function remains poorly defined. Although galaxamide increases the antitumor efficacy of cisplatin and protects ovarian function, its effects on uterine health are unknown. HeLa tumor‑bearing female mice received CIS alone or in combination with galaxamide. We assessed uterine morphology, systemic inflammation, endometrial epithelial cell apoptosis, endometrial receptivity factor expression, macrophage polarization, and NF-κB signaling. Cisplatin induced epithelial thinning and glandular disorganization; promoted apoptosis; decreased the expression of receptivity markers and desmosome and tight junction integrity; and elevated the serum levels of IL-6, IL-18, and TNF-α. Moreover, M1 macrophage infiltration and NF-κB pathway activation were observed. Cotreatment with galaxamide reduced cytokine levels, preserved uterine architecture, normalized apoptotic gene expression, restored receptivity marker expression, maintained desmosome/tight junction integrity, promote M2 macrophage polarization, and inhibited NF‑κB activation. In this study, cisplatin-induced uterine injury in tumor-bearing model mice was characterized. Galaxamide was demonstrated to attenuate this damage through antiapoptotic and anti-inflammatory actions mediated by inhibition of the NF-κB signaling pathway, suggesting its potential as a protective adjuvant to mitigate uterine toxicity during CIS‑based chemotherapy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Observation of the Cryoprotective Effect of Chlorogenic Acid on Spermatogonial Stem Cells Transplanted into of Testicular Torsion-Induced Azoospermia Model. 更正:绿原酸对睾丸扭转致无精子症模型移植精原干细胞冷冻保护作用的观察。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-02 DOI: 10.1007/s43032-026-02199-0
Sareh Khoshbakht, Azim Hedayatpour, Tayebeh Rastegar, Alireza Ebrahimzade Bideskan, Mohsen Mir, Mohammadreza Ebrahimzade, Samiullah Safi, Farnaz Khadivi
{"title":"Correction: Observation of the Cryoprotective Effect of Chlorogenic Acid on Spermatogonial Stem Cells Transplanted into of Testicular Torsion-Induced Azoospermia Model.","authors":"Sareh Khoshbakht, Azim Hedayatpour, Tayebeh Rastegar, Alireza Ebrahimzade Bideskan, Mohsen Mir, Mohammadreza Ebrahimzade, Samiullah Safi, Farnaz Khadivi","doi":"10.1007/s43032-026-02199-0","DOIUrl":"10.1007/s43032-026-02199-0","url":null,"abstract":"","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Redefining Cryopreservation Media: L-Methionine Boosts Post-Thaw Sperm Quality Across Fertility Status. 重新定义冷冻保存介质:l -蛋氨酸在生育状态下提高解冻后精子质量。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-07-30 DOI: 10.1007/s43032-026-02163-y
Madhan Kumar P, Parameswari R, Babujanarthanam R, Abilash D
{"title":"Redefining Cryopreservation Media: L-Methionine Boosts Post-Thaw Sperm Quality Across Fertility Status.","authors":"Madhan Kumar P, Parameswari R, Babujanarthanam R, Abilash D","doi":"10.1007/s43032-026-02163-y","DOIUrl":"10.1007/s43032-026-02163-y","url":null,"abstract":"<p><p>Cryopreservation, an integral aspect of assisted reproductive technology, negatively affects the sperm motility, viability, membrane integrity, and DNA stability through the induction of cryo-oxidative stress and damage to cellular function. L-methionine, a sulfur-containing amino acid with significant antioxidant potential, was examined for dose-dependent effects on post-thaw sperm quality in 85 semen samples (n = 43) fertile and (n = 42) infertile. The Fertile and Infertile semen samples were cryopreserved in media supplemented with L-methionine (1.5 mM, M1; 3 mM, M2; and 6 mM, M3) in comparison with commercial cryopreservation medium (CM). After the thawing, sperm motility, morphology, viability, plasma membrane and acrosome integrity, oxidative stress (MDA), antioxidant enzyme activity including superoxide dismutase (SOD) and catalase, and DNA fragmentation were evaluated. The 3 mM L-methionine (M2) group significantly promoted spermatozoa motility, progressive motility, viability, morphology, and acrosome integrity(p < 0.05) while reducing MDA levels and enhancing the activities of superoxide dismutase (SOD) and catalase (p < 0.001) as a strong antioxidant protection. The DNA fragmentation was lowest in the M2 group in fertile and infertile men. In contrast, the highest concentration tested (6 mM, M3) did not improve sperm quality parameters and was associated with reduced motility, viability, and increased DNA fragmentation, suggesting potential toxicity at higher concentrations. The ROC analysis showed M2 (AUC: 0.88 vs. commercial medium) to be much more sensitive for the diagnosis of sperm damage. This study suggests that supplementation with 3 mM L-methionine may serve as a promising cryoprotective strategy for improving post-thaw sperm quality, particularly in infertile men.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1714-1730"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrative Multi-Omics Analysis Identifies Key Molecular Targets Linking Bisphenol A Exposure to Gestational Diabetes Mellitus. 综合多组学分析确定双酚A暴露与妊娠糖尿病相关的关键分子靶点。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-08-04 DOI: 10.1007/s43032-026-02170-z
Lu Zheng, Xinying Song, Huiyan Wang, Wenbo Zhou
{"title":"Integrative Multi-Omics Analysis Identifies Key Molecular Targets Linking Bisphenol A Exposure to Gestational Diabetes Mellitus.","authors":"Lu Zheng, Xinying Song, Huiyan Wang, Wenbo Zhou","doi":"10.1007/s43032-026-02170-z","DOIUrl":"10.1007/s43032-026-02170-z","url":null,"abstract":"<p><p>Bisphenol A (BPA) exposure is associated with gestational diabetes mellitus (GDM); however, the underlying molecular mechanisms remain elusive. This study aimed to identify key genes mediating BPA exposure-related GDM through integrative bioinformatics analysis. We integrated BPA-related targets from multiple databases with GDM-associated genes derived from GeneCards and the GSE103552 dataset. Functional enrichment analysis was performed on the intersecting genes. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using four topological algorithms. Machine learning approaches were employed for feature selection. Immune infiltration was assessed, and core gene expression was validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR), additional GEO datasets, and single-cell RNA sequencing data. Thirty-four overlapping genes were identified and found to be enriched in the insulin signaling pathway, the AMPK pathway, and inflammatory responses. Following further screening, five core genes-HSPA8, NR3C1, ITGB1, NOTCH2, and POU5F1-were selected, demonstrating robust diagnostic performance. Immune analysis revealed significant correlations between hub genes and the infiltration levels of immune cells. Consistent expression patterns of ITGB1 and NOTCH2 were validated across additional GEO datasets. RT-qPCR confirmed the downregulation of HSPA8 and the upregulation of NR3C1 and NOTCH2 in GDM. Single-cell analysis corroborated cell-type-specific expression within the placenta. This study elucidates potential molecular links between BPA exposure and GDM, highlighting immune-metabolic dysregulation. The identified core genes may serve as biomarkers or therapeutic targets, thereby advancing precision environmental health strategies for pregnancy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1674-1686"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Live Birth Following Microdissection Testicular Sperm Extraction and Intracytoplasmic Sperm Injection: A Case Study of a Patient with Non-Obstructive Azoospermia and a Y-chromosome Microdeletion (Ym9; P3, Including AZFb, c Region). 显微解剖睾丸精子提取和卵胞浆内单精子注射后的活产:一例非阻塞性无精子症和y染色体微缺失(Ym9; P3,包括AZFb, c区)的病例研究。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-07-29 DOI: 10.1007/s43032-026-02160-1
Kei-Ichiro Uemura, Akira Nakashima, Hiro Furusaka-Kishimoto, Kyoko Kido, Kiyoaki Nishihara, Kosuke Ueda, Makoto Nakiri, Tsukasa Igawa
{"title":"Live Birth Following Microdissection Testicular Sperm Extraction and Intracytoplasmic Sperm Injection: A Case Study of a Patient with Non-Obstructive Azoospermia and a Y-chromosome Microdeletion (Ym9; P3, Including AZFb, c Region).","authors":"Kei-Ichiro Uemura, Akira Nakashima, Hiro Furusaka-Kishimoto, Kyoko Kido, Kiyoaki Nishihara, Kosuke Ueda, Makoto Nakiri, Tsukasa Igawa","doi":"10.1007/s43032-026-02160-1","DOIUrl":"10.1007/s43032-026-02160-1","url":null,"abstract":"<p><p>The azoospermia factor (AZF) region on the long arm of the Y chromosome is instrumental in spermatogenesis. In particular, complete deletion of the AZFa, AZFb, and AZFb + c regions is not an indication for microdissection testicular sperm extraction (MD-TESE) as there is no chance of sperm retrieval. This report presents a rare case of a successful live birth, following intracytoplasmic sperm injection (ICSI) using sperm from a patient with a microdeletion of the Y chromosome, including part of the AZFb, c region, who underwent MD-TESE. A 3X-year-old Japanese man with azoospermia was admitted to our hospital in October X. Scrotal ultrasonography, physical examination, and genetic examination resulted in a diagnosis of non-obstructive azoospermia with Y chromosomal microdeletion of Ym-9 P3 (deletion of sequence-tagged site markers [sY2990][sY1197][sy1191], including part of the AZFb region). Thus, ICSI resulted in a successful fertilization and the subsequent birth of a child, suggesting its potential application in the field of in vitro fertilization.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1700-1704"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Risk Score for Polycystic Ovary Syndrome Based on Meta-Analysis and Machine Learning of Gut Microbiota Signatures. 基于肠道微生物群特征的meta分析和机器学习的多囊卵巢综合征风险评分。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-06-19 DOI: 10.1007/s43032-026-02129-0
Panwang Huang, Ye Li, Fan-Sheng Kong, Tao Guo, Jin-Ping Yao, Jian-Huan Chen, Yaping Ma
{"title":"A Risk Score for Polycystic Ovary Syndrome Based on Meta-Analysis and Machine Learning of Gut Microbiota Signatures.","authors":"Panwang Huang, Ye Li, Fan-Sheng Kong, Tao Guo, Jin-Ping Yao, Jian-Huan Chen, Yaping Ma","doi":"10.1007/s43032-026-02129-0","DOIUrl":"10.1007/s43032-026-02129-0","url":null,"abstract":"<p><p>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder among reproductive-age women, in which emerging evidence suggests a substantial role played by the gut microbiota. To comprehensively evaluate gut microbiota alterations in PCOS and identify microbial biomarkers through integrated analysis, a systematic search of PubMed, Web of Science, and Embase was conducted for studies employing 16S rRNA gene sequencing of fecal samples from PCOS cohorts. Ten eligible PCOS cohorts, comprising 858 individuals, were included in the study, from which a risk score was derived using a 20-gene gut microbial signature associated with PCOS. Meta-analysis at the genus level identified that Subdoligranulum, NK4A214_group, and Collinsella significantly decreased, and Bacteroides increased in PCOS across multiple cohorts. Machine learning analysis identified a 20-genus microbial signature using the least absolute shrinkage and selection operator (LASSO) method, which was used to construct a risk score with an AUC of 0.835 in diagnosis prediction. Network analysis further identified Negativibacillus and Lachnospiraceae_UCG_010 as potential driver microbes in PCOS. The analysis in this study highlights key alterations in the gut microbiota across PCOS cohorts. The identified gut microbial signature and derived LASSO-based risk model offer novel insights and a potential tool for PCOS diagnosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1804-1815"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Postnatal Developmental Localization of Vaspin/GRP78 in the Mouse Pituitary and its Evidence in Gonadotrophin Secretion. 小鼠垂体中Vaspin/GRP78的产后发育定位及其在促性腺激素分泌中的作用
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-07-28 DOI: 10.1007/s43032-026-02162-z
Preethi Riba, Guruswami Gurusubramanian, Vikas Kumar Roy
{"title":"Postnatal Developmental Localization of Vaspin/GRP78 in the Mouse Pituitary and its Evidence in Gonadotrophin Secretion.","authors":"Preethi Riba, Guruswami Gurusubramanian, Vikas Kumar Roy","doi":"10.1007/s43032-026-02162-z","DOIUrl":"10.1007/s43032-026-02162-z","url":null,"abstract":"<p><p>Adipokine, vaspin, and its receptor GRP78 play an important role in reproductive and metabolic functions. Both proteins are expressed in reproductive tissues like the testis, ovary, and also in the hypothalamus. Our recent study has reported its postnatal localization in the testis, suggesting its involvement in the local reproductive role in pubertal males. This study investigated the postnatal localization of vaspin and GRP78 at different developmental stages of the pituitary. The study includes in vivo 35-day exogenous vaspin treatment in adult male mice (0.1 µg/kg and 1 µg/kg) and whole pituitary explant cultured with vaspin, GnRH agonist, and HA15 (GRP78 inhibitor, 12 µM) in vitro. Both vaspin and GRP78 showed strong immunostaining at PND65, and both were shown to co-express within the anterior pituitary. The exogenous vaspin treatment significantly increases the circulating LH, FSH, GnRH, and testosterone levels at higher doses, along with increased AR expression. Also, the hypothalamic Gnrh1 expression increased in both doses of vaspin. In vitro vaspin treatment increased the basal secretion of LH and FSH from the whole pituitary. The study provides the first suggestive evidence on vaspin-mediated gonadotrophin secretion. Moreover, GRP78 inhibition using HA15 decreased mRNA expression of Lhβ and Fshβ in the pituitary. Their expression was increased after co-treatment with vaspin, suggesting the involvement of GRP78-mediated action in pituitary gonadotrophin secretion. Furthermore, the study has also reported the co-localization of LH and FSH with vaspin and GRP78.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1794-1803"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Astaxanthin and Male Reproductive Health: Mechanisms, Experimental Evidence, and Clinical Perspectives. 虾青素与男性生殖健康:机制、实验证据和临床观点。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-08-21 DOI: 10.1007/s43032-026-02177-6
Ali Mokhtari, Marziyeh Tavalaee, Nushin Naderi, Amir-Ali Dadkhah, Omidreza Sedig, Mohammad Hossein Nasr-Esfahani
{"title":"Astaxanthin and Male Reproductive Health: Mechanisms, Experimental Evidence, and Clinical Perspectives.","authors":"Ali Mokhtari, Marziyeh Tavalaee, Nushin Naderi, Amir-Ali Dadkhah, Omidreza Sedig, Mohammad Hossein Nasr-Esfahani","doi":"10.1007/s43032-026-02177-6","DOIUrl":"10.1007/s43032-026-02177-6","url":null,"abstract":"<p><p>Oxidative stress is a primary driver of male infertility, underscoring the critical importance of effective antioxidant defense systems in maintaining reproductive function. Astaxanthin, a xanthophyll carotenoid with potent free radical-scavenging capacity and membrane-stabilizing properties, has garnered interest as a therapeutic agent for male reproductive health. Experimental evidence indicates that astaxanthin modulates cellular redox homeostasis, preserves mitochondrial integrity, and attenuates lipid peroxidation in spermatozoa and testicular cells. Through these mechanisms, it potentially maintains sperm structural integrity and functional competence under oxidative stress. Preclinical studies demonstrate that astaxanthin supplementation enhances sperm quality, supports mitochondrial bioenergetics, and protects against testicular oxidative injury. However, clinical evidence in men remains limited and heterogeneous, with variations in study populations, treatment durations, dosages, and outcome measures. Although some clinical investigations report improvements in semen parameters and markers of oxidative stress, others lack consistent findings. Consequently, these clinical data must be interpreted with caution. This narrative review synthesizes knowledge on the biological mechanisms through which astaxanthin influences male reproductive physiology, including oxidative regulation and stress response modulation. It evaluates existing data, identifies significant knowledge gaps, and highlights research priorities. To clarify the therapeutic utility of astaxanthin in male infertility, well-designed, large-scale randomized controlled trials featuring standardized formulations and robust clinical outcomes are required.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1747-1759"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prenatal Androgenization Modifies H3K9me3 Binding in the Promoter of the Androgen Receptor Gene in the Arcuate Nucleus of the Adult Female Mouse. 产前雄激素化改变成年雌性小鼠弓形核雄激素受体基因启动子中H3K9me3的结合
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-08-21 DOI: 10.1007/s43032-026-02174-9
Yugo Watanabe, Kelly A Glendining, Lorryn Fisher, Rebecca E Campbell, Christine L Jasoni
{"title":"Prenatal Androgenization Modifies H3K9me3 Binding in the Promoter of the Androgen Receptor Gene in the Arcuate Nucleus of the Adult Female Mouse.","authors":"Yugo Watanabe, Kelly A Glendining, Lorryn Fisher, Rebecca E Campbell, Christine L Jasoni","doi":"10.1007/s43032-026-02174-9","DOIUrl":"10.1007/s43032-026-02174-9","url":null,"abstract":"<p><p>Animal models have shown that prenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS) features. We have identified that prenatally androgenized (PNA) mice modelling PCOS show suppressed androgen receptor mRNA (Ar) expression in the arcuate nucleus (ARC) across development. This could contribute to PCOS-related impaired gonadal steroid hormone feedback to GnRH neurons. However, the mechanism of Ar mRNA suppression following PNA is not determined. We performed a chromatin immunoprecipitation (ChIP) assay coupled with quantitative PCR (qPCR) to investigate histone and transcription factor binding within the Ar gene promoter or enhancer regions in the ARC of female mice at postnatal day (P)60 or gestational day (GD)18.5. In comparison to adult vehicle control (VEH) mice, our ChIP-qPCR revealed that H3K9me3, a repressive histone mark, was increased in adult PNA mice at the promoter regions of the Ar gene. H3K27ac, an active histone mark, and SP1, a transcription factor that acts as a positive regulator of gene expression, were unchanged in the same regions. Increased H3K9me3 seen at the promoter region in adult PNA mice, however, was not observed in the GD18.5 mice ARC following PNA. These results suggest that the deposition of H3K9me3 on the Ar promoter is unlikely to be established by PNA at the time of excess androgen exposure, and instead is likely to be established later in postnatal development or in adulthood. These data provide greater understanding of the developmental mechanisms and timeline underpinning PNA-mediated female dysfunction and PCOS-like reproductive physiology.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1775-1782"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
INSL3 Preserves Male Reproductive Function Under Inflammatory and Glucocorticoid Stress in Rats. INSL3在炎症和糖皮质激素应激下保护雄性大鼠生殖功能。
IF 2.8 3区 医学
Reproductive Sciences Pub Date : 2026-09-01 Epub Date: 2026-08-07 DOI: 10.1007/s43032-026-02164-x
Gulfidan Coskun, Tugce Sapmaz, Dilek Saker, Samet Kara, Leman Sencar, Yusuf Dogus, Sait Polat
{"title":"INSL3 Preserves Male Reproductive Function Under Inflammatory and Glucocorticoid Stress in Rats.","authors":"Gulfidan Coskun, Tugce Sapmaz, Dilek Saker, Samet Kara, Leman Sencar, Yusuf Dogus, Sait Polat","doi":"10.1007/s43032-026-02164-x","DOIUrl":"10.1007/s43032-026-02164-x","url":null,"abstract":"<p><p>Rheumatoid arthritis and its glucocorticoid-based treatment may adversely affect male reproductive function by disrupting spermatogenesis, steroidogenesis, and testicular homeostasis. Insulin-like peptide 3 (INSL3), a Leydig cell-derived peptide hormone and marker of Leydig cell functional capacity, may contribute to the maintenance of testicular function through its steroidogenic and anti-inflammatory effects. In the present study, we investigated the effects of prednisolone and INSL3, administered alone or in combination, on testicular structure and function in rats with adjuvant-induced arthritis. Adult male rats were allocated to seven groups: control, prednisolone, INSL3, arthritis, arthritis + prednisolone, arthritis + INSL3, and arthritis + prednisolone + INSL3. Testicular alterations were evaluated using histological, morphometric, immunohistochemical, ultrastructural, testosterone, and sperm analyses. Arthritis was associated with reduced testicular weight, decreased seminiferous tubule diameter and epithelial thickness, impaired sperm parameters, lower serum and intratesticular testosterone levels, increased testicular tumor necrosis factor-α and interleukin-6 immunoreactivity, and reduced 3β-hydroxysteroid dehydrogenase and proliferating cell nuclear antigen immunoreactivity. In arthritic rats, prednisolone or INSL3 alone was associated with partial improvement in selected testicular parameters, whereas combined treatment was associated with improvement across several inflammatory, morphometric, steroidogenic, and sperm-related parameters. These findings suggest that INSL3 treatment is associated with partial attenuation of inflammation-related testicular injury and improvement in selected reproductive parameters under inflammatory and glucocorticoid stress. Further studies are required to clarify whether these effects are mediated by direct intratesticular mechanisms or indirect systemic pathways.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1731-1746"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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