Qingyu Zhang, Xin Wu, Xinli Liu, Jinyan Wei, Li Wang, Jun Cao, Xiaolin Lu
{"title":"Dysregulation of SCARB1 Alternative Splicing Disturbs Amino Acid Metabolism in Anembryonic Pregnancy.","authors":"Qingyu Zhang, Xin Wu, Xinli Liu, Jinyan Wei, Li Wang, Jun Cao, Xiaolin Lu","doi":"10.1007/s43032-026-02179-4","DOIUrl":"https://doi.org/10.1007/s43032-026-02179-4","url":null,"abstract":"<p><p>Anembryonic pregnancy (AP) accounts for a notable proportion of all first-trimester spontaneous miscarriage. Alternative splicing has been implicated in placental development and spontaneous abortion. However, the role of alternative splicing in modulating amino acid metabolism in AP remains unclear. We employed mass spectrometry to measure the levels of amino acids and metabolites in the serum of AP patients and healthy controls. RNA-Seq and rMATS were utilized to evaluate the alternative splicing profiles of chorionic villi from the two groups. Key splicing events in PRKCD, SCARB1, and METTL2B were subsequently validated by splicing-specific PCR. An integrated analysis, incorporating transcription factor prediction and publicly available datasets, was performed to explore the potential mechanisms by which alternative splicing may contribute to the metabolic disturbances in AP. Mass spectrometry analysis confirmed dysregulated of amino acid metabolism in AP. Compared to controls, AP patients exhibited 903 differentially alternative splicing genes and 558 differentially expressed genes, with skipping exons as the predominant alternative splicing type. Notably, PRKCD, SCARB1, and METTL2B displayed the most significant splicing changes, with preferential exon inclusion in AP samples. Motif analysis predicted that SCARB1 was a potential target gene of transcription factor TEAD4. Functional studies revealed that both SCARB1 and TEAD4 were involved in metabolism regulation, including amino acid and lipid metabolism. Our study demonstrates that dysregulation of alternative splicing in SCARB1 may contribute to AP by disrupting metabolic homeostasis, particularly amino acid metabolism. These findings highlight alternative splicing-mediated metabolic reprogramming as a potential mechanistic underpinning of AP.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031120","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}
{"title":"MicroRNA-122-5p Targets FOXO3 to Mediate Podocyte Senescence and Proteinuria Induced by Angiotensin II Type 1 Receptor Autoantibodies in Preeclampsia.","authors":"Guoli Xu, Zhenhao Yang, Yuan Liu, Chen Zong, Xiaoqing Zhong, Yuxuan Zhou, Di Zhao, Chenhui Zhang, Liwen Zhang, Lin Yang, Jianying Niu","doi":"10.1007/s43032-026-02198-1","DOIUrl":"https://doi.org/10.1007/s43032-026-02198-1","url":null,"abstract":"<p><p>Preeclampsia (PE) drives irreversible podocyte depletion, predisposing patients to a heightened long-term risk of chronic kidney disease. While premature cellular senescence underlies this structural loss, the specific preeclamptic factors triggering this mechanism remain incompletely defined. We investigated the role of the angiotensin II type 1 receptor agonistic autoantibody (AT1-AA)-a central circulating pathogenic factor in PE-in promoting podocyte senescence through post-transcriptional pathways. We first interrogated public clinical transcriptomic datasets and validated the findings using clinical urine specimens from PE patients to identify key dysregulated microRNAs in PE. We then integrated in vitro mechanistic assays using human podocytes with an in vivo AT1-AA-infused pregnant mouse model. The regulatory cascade was validated via dual-luciferase reporter assays. The therapeutic efficacy of targeting this pathway was evaluated via systemic administration of a specific microRNA inhibitor (AntagomiR-122-5p). Bioinformatic analysis and clinical validation revealed that miR-122-5p is upregulated in PE patients. In vivo, AT1-AA exposure provoked classic PE manifestations, including severe hypertension, albuminuria, and podocyte foot process effacement. This pathology was driven by podocyte-specific senescence, evidenced by nuclear p21 accumulation and a senescence-associated secretory phenotype (SASP). Mechanistically, AT1-AA triggered a toxic accumulation of mitochondrial reactive oxygen species (mtROS) by upregulating miR-122-5p, which directly repressed the FOXO3/SOD2 antioxidant defense system. Targeted in vivo inhibition of miR-122-5p yielded dual therapeutic benefits: it attenuated the elevation in maternal systolic blood pressure and conferred direct cytoprotection to the glomerular filtration barrier. AntagomiR-122-5p effectively reversed glomerular senescence, suppressed local inflammatory cytokines, and restored podocyte ultrastructure. AT1-AA governs preeclamptic podocyte senescence and proteinuria by suppressing the FOXO3/SOD2 signaling axis via clinically relevant miR-122-5p. Systemic antagonism of miR-122-5p offers a comprehensive therapeutic strategy to simultaneously alleviate maternal hypertension and protect the renal filtration barrier from permanent structural decline.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025743","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}
Amir Ajoolabady, Bonglee Kim, Jaakko Tuomilehto, Domenico Pratico, Jun Ren, Abdel Halim Harrath
{"title":"Pyroptosis in Patients with Ovarian Dysfunction and Infertility: Molecular Mechanisms and Therapeutics.","authors":"Amir Ajoolabady, Bonglee Kim, Jaakko Tuomilehto, Domenico Pratico, Jun Ren, Abdel Halim Harrath","doi":"10.1007/s43032-026-02208-2","DOIUrl":"https://doi.org/10.1007/s43032-026-02208-2","url":null,"abstract":"<p><p>Pyroptosis is a caspase-dependent, inflammatory programmed form of cell death that is evolutionarily conserved among eukaryotic cells. Increasing evidence indicates that pyroptosis plays significant pathological roles in various human diseases and inflammatory conditions. Infertility, particularly female infertility, and ovarian dysfunction are closely associated with inflammation, with recent findings pinpointing a role for pyroptosis in the pathogenesis of these pathologies. Accordingly, this narrative review aims to provide an updated overview of recent discoveries elucidating the role of pyroptosis in ovarian infertility and related diseases, the underlying molecular mechanisms and signaling pathways involved, and emerging therapeutic compounds with the potential to inhibit pyroptosis and alleviate ovarian infertility and diseases. In addition, we highlight key research gaps and propose future directions that warrant further investigation.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025783","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}
{"title":"Taurine Attenuates Repeated Heat Stress-Induced Male Reproductive Dysfunction in Mice: Associations with HPG Axis Homeostasis and Hypothalamic Microglial Changes.","authors":"Bin Li, Ruixi Ming, Yumeng Liu, Hongzhou Guo","doi":"10.1007/s43032-026-02209-1","DOIUrl":"https://doi.org/10.1007/s43032-026-02209-1","url":null,"abstract":"<p><p>Heat stress (HS)-induced male reproductive dysfunction is usually interpreted within a testis-centered framework, whereas the contribution of central neuroendocrine disturbance remains less well defined. In the present study, a repeated HS mouse model was used to examine whether taurine pretreatment attenuates reproductive dysfunction by integrating local testicular endpoints with HPG-axis-related and hypothalamic inflammatory readouts. Male C57BL/6J mice were assigned to control, HS + vehicle, and HS + taurine groups. Mice in the HS groups were exposed to 40 ± 1 °C for 1 h daily for 14 consecutive days, and taurine was administered intraperitoneally before each heat exposure. Sperm parameters, testicular histopathology, inflammatory, oxidative, apoptotic, endocrine, and hypothalamic microglial endpoints were assessed. Repeated HS impaired sperm motility and concentration, increased abnormal sperm morphology, and caused marked histopathological injury in the testes. These changes were accompanied by increased testicular inflammation, oxidative stress, and apoptosis. HS also disrupted HPG-axis hormone homeostasis, as reflected by altered hypothalamic Gnrh expression, pituitary Lhb and Fshb expression, and circulating reproductive hormone levels. In parallel, repeated HS was associated with hypothalamic microglial activation, increased inflammatory responses, and increased microglia-GnRH overlap. Taurine pretreatment significantly attenuated sperm dysfunction and testicular injury, reduced inflammatory, oxidative, and apoptotic alterations, partially restored endocrine homeostasis, and reduced hypothalamic microglial responses. Together, these findings show that taurine alleviates repeated HS-induced male reproductive dysfunction with coordinated improvements in testicular injury, endocrine imbalance, and hypothalamic inflammatory responses. However, the hypothalamic findings are associative and do not establish causality.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025796","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}
Havva Betul Bacak, Fatma Ketenci Gencer, Enes Serhat Coskun, Fatih Irice, Yağmur Aciyiyen, Hayat Terkan, Ecenur Celikoglu Berker, Sinem Deligozoglu, Serkan Kumbasar, Suleyman Salman
{"title":"Association of Maternal Thyroid-stimulating Hormone Levels with Psychological Well-being, Sexual Function, and Quality of Life During Pregnancy.","authors":"Havva Betul Bacak, Fatma Ketenci Gencer, Enes Serhat Coskun, Fatih Irice, Yağmur Aciyiyen, Hayat Terkan, Ecenur Celikoglu Berker, Sinem Deligozoglu, Serkan Kumbasar, Suleyman Salman","doi":"10.1007/s43032-026-02206-4","DOIUrl":"https://doi.org/10.1007/s43032-026-02206-4","url":null,"abstract":"<p><p>We primarily investigated whether depressive and anxiety symptoms, sexual function, and quality of life differed between pregnant women grouped using a predefined maternal thyroid-stimulating hormone (TSH) cutoff of 2.5 mIU/L, with complementary continuous analyses used to characterize the TSH-outcome relationships. In this prospective single-center observational cohort (November 2025-January 2026), 208 pregnant women attending antenatal care completed the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Arizona Sexual Experiences Scale (ASEX), and the 13-item Quality of Life Short Form (YKK-13) before physician evaluation and blood sampling. After predefined exclusions (including autoimmune thyroid disease and thyroid-related medication use) and endocrinology consultation for TSH ≥ 2.5 mIU/L, 192 participants were included (TSH < 2.5 mIU/L, n = 102; TSH ≥ 2.5 mIU/L, n = 90) with complete questionnaire data. Baseline age, gestational age, gravida, parity, and body mass index were similar between groups. Median BDI and BAI scores were higher in the TSH ≥ 2.5 mIU/L group than in the TSH < 2.5 mIU/L group (BDI: 13.0 vs 10.0; p = 0.002; BAI: 11.0 vs 8.0; p = 0.009). YKK-13 and ASEX scores showed no statistically significant between-group differences (p = 0.068 for YKK-13 and p = 0.400 for ASEX). In exploratory pairwise analyses, the first detectable difference in BDI was observed for TSH < 2.5 versus 2.5- < 4.5 mIU/L (p = 0.007), while comparisons between 2.5- < 4.5 and ≥ 4.5 mIU/L were not significant for BDI, BAI, YKK-13, or ASEX (all p > 0.05). In complementary analyses treating TSH as a continuous variable, higher maternal TSH was weakly but monotonically associated with higher depression and anxiety scores and lower quality of life, with no evidence of a nonlinear or threshold-like relationship. Maternal TSH ≥ 2.5 mIU/L was associated with higher depressive and anxiety symptom scores in unadjusted comparisons, whereas sexual function and quality-of-life scores were broadly comparable across TSH strata. Given the absence of FT4 and thyroid autoantibody measurements, the use of a fixed pragmatic TSH cutoff, the lack of trimester-specific reference intervals, and the absence of multivariable adjustment, these findings should be interpreted as exploratory and hypothesis-generating rather than as evidence of an independent or causal association.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017747","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}
Asli Metin Mahmutoglu, Mehmet Caniklioglu, Aysen Caniklioglu, Emin Kaymak, Yuksel Terzi
{"title":"Sperm tRNA-Derived Fragment-36 Expression in Varicocele: Associations with Disease Severity, Semen Parameters and Reproductive Hormones.","authors":"Asli Metin Mahmutoglu, Mehmet Caniklioglu, Aysen Caniklioglu, Emin Kaymak, Yuksel Terzi","doi":"10.1007/s43032-026-02210-8","DOIUrl":"https://doi.org/10.1007/s43032-026-02210-8","url":null,"abstract":"<p><p>Varicocele is a prevalent and potentially reversible cause of male infertility; however, the molecular mechanisms underlying its pathogenesis remain poorly understood. Transfer RNA-derived fragments (tRFs) have emerged as important regulators of reproductive and vascular dysfunction, yet their role in varicocele has not been explored. This study aimed to evaluate the expression of tRF-23, tRF-36 and tRF-40 in spermatozoa from men with varicocele and healthy controls, and to determine whether their expression is associated with reproductive hormone levels and semen quality. Blood and semen samples were collected from 60 patients with clinically graded varicocele (n = 20 per grade) and 20 controls. Expression levels of tRFs were quantified using qRT-PCR. All three tRFs were detected in spermatozoa from both patients and controls. Relative to controls, tRF-23 and tRF-36 expression levels were increased by 1.23-fold and 1.52-fold, respectively, whereas tRF-40 expression was reduced to 0.9-fold; however, these differences did not reach statistical significance (p > 0.05). Stratification by varicocele grade revealed a distinct expression pattern for tRF-36, which was significantly downregulated in grade III compared with grade I varicocele patients (4.52-fold decrease, p = 0.010). Correlation analyses demonstrated significant associations among the three tRFs, and all were negatively correlated with sperm concentration. Collectively, these findings provide the first evidence linking tRF expression to varicocele and suggest a potential role for tRFs in the molecular pathology of this condition.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017761","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}
{"title":"Correction to: Deciphering the Role of ZEB1 as a Central Regulator of Epithelial-Mesenchymal Transition and Hormonal Resistance in Endometriosis.","authors":"Sanket Shirodkar, Gaurav Doshi","doi":"10.1007/s43032-026-02212-6","DOIUrl":"10.1007/s43032-026-02212-6","url":null,"abstract":"","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983422","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}
{"title":"Dual Roles of Autophagy in Endometrial Fibrosis and Its Implications in Age-Related Reproductive Dysfunction.","authors":"Hiroshi Kobayashi","doi":"10.1007/s43032-026-02192-7","DOIUrl":"https://doi.org/10.1007/s43032-026-02192-7","url":null,"abstract":"<p><p>With the increasing prevalence of pregnancies at advanced maternal age, elucidating the molecular mechanisms underlying reproductive aging has become an important clinical challenge. In addition to ovarian aging, accumulating evidence suggests that age-related alterations in the endometrium contribute to impaired implantation and adverse reproductive outcomes. Autophagy, a highly conserved intracellular quality-control system, regulates mitochondrial homeostasis, metabolism, inflammation, and tissue remodeling. This review summarizes current evidence regarding the role of autophagy in endometrial fibrosis associated with reproductive aging. We first outline the general molecular mechanisms of autophagy-mediated fibrosis based on studies in multiple organs and then critically evaluate evidence specific to the endometrium. Impaired autophagy promotes oxidative stress, mitochondrial dysfunction, cellular senescence, epithelial-mesenchymal transition, fibroblast-to-myofibroblast transition, and extracellular matrix accumulation, thereby contributing to fibrotic remodeling and reduced endometrial receptivity. Conversely, under specific cellular and microenvironmental conditions, autophagy may facilitate profibrotic remodeling, highlighting its context-dependent dual role. We further discuss current evidence, limitations, and future research priorities, emphasizing the distinction between mechanisms established in the endometrium and concepts extrapolated from other organs. A better understanding of cell type-specific and age-dependent autophagy may facilitate the development of biomarkers and safe therapeutic strategies for endometrial fibrosis and reproductive aging.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977936","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}
Bahadır Codal, Ahmet Kurt, Hacer Kaplan, Ayberk Çakır, Burak Hızlı, Mustafa Raşit Özler
{"title":"Circulating Fatty Acid-Binding Protein 4 (FABP4) in Adolescents with Polycystic Ovary Syndrome: Metabolic Correlates and Diagnostic Performance.","authors":"Bahadır Codal, Ahmet Kurt, Hacer Kaplan, Ayberk Çakır, Burak Hızlı, Mustafa Raşit Özler","doi":"10.1007/s43032-026-02189-2","DOIUrl":"https://doi.org/10.1007/s43032-026-02189-2","url":null,"abstract":"<p><p>To compare circulating fatty acid-binding protein 4 (FABP4) concentrations in adolescents with polycystic ovary syndrome (PCOS) and controls, examine its metabolic correlates, and evaluate its diagnostic performance. This prospective observational study included 88 adolescents (44 PCOS, 44 controls) aged 10-19 years. PCOS was diagnosed using 2023 ESHRE/ASRM criteria. Clinical, anthropometric, and biochemical parameters were assessed. Serum FABP4 was measured via ELISA. Statistical analyses included multivariable linear regression, Firth's penalized logistic regression, and receiver operating characteristic (ROC) curves. Median FABP4 levels were significantly higher in adolescents with PCOS compared to controls (5.74 vs. 3.59 ng/mL, p < 0.001). Multivariable linear regression demonstrated that PCOS status, body mass index (BMI), and insulin resistance (HOMA-IR) associated with higher FABP4 concentrations. Multivariable logistic regression identified free androgen index (FAI) and FABP4 as variables independently associated with PCOS. ROC analysis showed FABP4 (> 4.08 ng/mL) yielded an area under the curve (AUC) of 0.849 (81.8% sensitivity, 75.0% specificity). The combination of FABP4 and FAI improved model discrimination compared with FAI alone (ΔAUC = 0.133, p = 0.001), and this improvement remained significant after BMI adjustment. Circulating FABP4 is elevated in adolescents with PCOS and is associated with PCOS status, BMI, and insulin resistance. In this cohort, FABP4 provided complementary metabolic information when interpreted alongside FAI; however, BMI-matched, body composition-characterized, and externally validated studies are needed before FABP4 can be considered a clinically generalizable adjunctive biomarker in adolescent PCOS.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970993","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}
Seyma Donmez Sahıp, Mehmet Mustafa Eyol, Ekin Ersoy, Elif Erden Deveci, Ibrahim Bugra Bahadır, Batuhan Turgay
{"title":"Serum Prostate-Specific Antigen Concentrations in Polycystic Ovary Syndrome: A Comparative Analysis of Hirsute and Non-Hirsute Phenotypes.","authors":"Seyma Donmez Sahıp, Mehmet Mustafa Eyol, Ekin Ersoy, Elif Erden Deveci, Ibrahim Bugra Bahadır, Batuhan Turgay","doi":"10.1007/s43032-026-02187-4","DOIUrl":"https://doi.org/10.1007/s43032-026-02187-4","url":null,"abstract":"<p><strong>Objective: </strong>Polycystic ovary syndrome (PCOS), affecting 5-10% of reproductive-aged women, is marked by anovulation and hyperandrogenism. Prostate-specific antigen (PSA), traditionally a prostate cancer biomarker, has also been detected in female tissues and proposed as a marker of androgen activity. This study examined whether serum total and free PSA differ between hirsute and non-hirsute PCOS phenotypes, hypothesizing higher levels in the hirsute group.</p><p><strong>Methods: </strong>In this prospective case-control study, 90 women with PCOS diagnosed by the 2003 Rotterdam ESHRE/ASRM criteria were enrolled between May 2022 and January 2023. Participants were stratified into hirsute and non-hirsute groups using the modified Ferriman-Gallwey score. Demographic, clinical, and reproductive data were recorded, and venous blood samples collected on cycle days 2-3 were analyzed for PSA, androgens, and metabolic parameters. Insulin resistance was assessed using homeostatic model assessment of insulin resistance (HOMA-IR).</p><p><strong>Results: </strong>Age did not differ between groups, but body mass index (BMI) (p = 0.044), acne prevalence (p = 0.032), and free testosterone (p = 0.014) were significantly higher in hirsute women. Amenorrhea and oligomenorrhea were more frequent in the non-hirsute group (p = 0.012). Ovarian morphology, alopecia, and PSA levels showed no significant differences between groups (all p > 0.05). However, Spearman rank correlation analysis revealed significant positive correlations between PSA and Ferriman-Gallwey score (r<sub>s</sub> = 0.896, p < 0.001), total testosterone (r<sub>s</sub> = 0.779, p < 0.001), HOMA-IR (r<sub>s</sub> = 0.838, p < 0.001), DHEA-S (r<sub>s</sub> = 0.807, p < 0.001), and LH (r<sub>s</sub> = 0.804, p < 0.001).</p><p><strong>Conclusions: </strong>Hirsute phenotypes demonstrated clustered hyperandrogenic features, including higher free testosterone, BMI, and acne prevalence. Although PSA levels did not differ between phenotypic groups, the significant positive correlations with hirsutism score and metabolic parameters suggest that PSA may reflect androgenic-metabolic activity in PCOS, underscoring the heterogeneity of the syndrome and the need for comprehensive phenotypic assessment.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970915","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}