{"title":"Beyond body mass index: A contemporary review of obesity and female infertility.","authors":"Jongeun Han, Kyung Jin Lee, Seulki Kim","doi":"10.5653/cerm.2026.010048","DOIUrl":"https://doi.org/10.5653/cerm.2026.010048","url":null,"abstract":"<p><p>Obesity is increasingly understood as a reproductive-metabolic condition that can affect female fertility across the continuum from natural conception to assisted reproductive technology (ART). Excess adiposity may disrupt hypothalamic-pituitary-ovarian regulation, insulin signaling, inflammatory pathways, ovarian function, oocyte competence, embryo development, and endometrial receptivity. This review synthesizes current evidence linking obesity with infertility, reduced ART efficiency, implantation failure, miscarriage, and reduced live birth, while emphasizing that these associations vary according to reproductive and metabolic phenotype. Particular attention is given to polycystic ovary syndrome, advanced age, diminished ovarian reserve, recurrent implantation failure, and recurrent pregnancy loss. Pre-treatment weight-loss strategies, including lifestyle intervention, glucagon-like peptide-1 receptor agonists, tirzepatide, and bariatric surgery, are also considered in relation to reproductive benefit, treatment delay, and pregnancy safety. Overall, obesity should not be treated simply as a body mass index category, but rather as a phenotype-dependent reproductive-metabolic condition that requires individualized fertility-treatment planning.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of installing a volatile organic compound-removal filter in a clinical embryology laboratory on embryo development.","authors":"Koji Sakamoto, Yusuke Sagae, Masako Imano, Shoko Sakai, Yoshimi Kitawaki, Asuka Okunomiya, Masaki Mandai, Akihito Horie","doi":"10.5653/cerm.2026.09369","DOIUrl":"https://doi.org/10.5653/cerm.2026.09369","url":null,"abstract":"<p><strong>Objective: </strong>Improving embryo quality is essential for increasing pregnancy and live birth rates in assisted reproductive technology (ART). The culture environment strongly influences embryo quality, and air quality is one of its key components. Volatile organic compounds (VOCs) present in clinical embryology laboratories and incubators have been suggested to adversely affect gametes and embryos. This study examined whether installing a VOC-removal filter in a clinical embryology laboratory affected fertilization rate, cleavage rate, blastocyst formation rate, and good-quality blastocyst rate.</p><p><strong>Methods: </strong>A VOC-removal filter was installed in the clinical embryology laboratory to reduce ambient VOC concentrations. Embryological outcomes before and after filter installation were compared in both in vitro fertilization and intracytoplasmic sperm injection (ICSI) cycles. The evaluated outcomes were fertilization rate, cleavage rate, blastocyst formation rate, and good-quality blastocyst rate.</p><p><strong>Results: </strong>VOC concentrations decreased after filter installation; however, blastocyst formation rates did not differ significantly between the pre-installation and post-installation periods. In analyses restricted to ICSI cycles, the proportion of good-quality blastocysts was significantly higher after filter installation than before installation (p=0.0069).</p><p><strong>Conclusion: </strong>These findings suggest that VOCs in the clinical embryology laboratory may adversely affect embryo quality, particularly in ICSI cycles, which involve relatively prolonged laboratory handling. Management of VOC concentrations may therefore be an important component of efforts to improve embryo culture conditions in ART.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Funda Dağıstanlı, Mustafa Ayhan Ekici, Dilara Boztaş Engin
{"title":"Comparison of a single dose of follitropin alfa administered before or after clomiphene citrate in the treatment of unexplained infertility.","authors":"Funda Dağıstanlı, Mustafa Ayhan Ekici, Dilara Boztaş Engin","doi":"10.5653/cerm.2025.09117","DOIUrl":"https://doi.org/10.5653/cerm.2025.09117","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy of a single 150 international unit (IU) dose of follitropin alfa (FA), administered either before or after clomiphene citrate (CC), in women with unexplained infertility.</p><p><strong>Methods: </strong>This prospective interventional study included 105 patients allocated to four groups. Group 1 received CC 100 mg/day on cycle days 3-7. Group 2 received a single 150-IU dose of FA on day 3, followed by CC on days 4-8. Group 3 received CC 100 mg/day on days 3-7, followed by a single 150-IU dose of FA on day 8. Group 4 received only a single 150-IU dose of FA on day 3. The primary outcomes were pregnancy rate (PR) and risk of ovarian hyperstimulation syndrome (OHSS), and the secondary outcome was ovulation rate (OR).</p><p><strong>Results: </strong>No ovulation was observed in the single-dose FA group. Group 1 had a PR of 11.4%, an OR of 94.3%, and an OHSS risk of 5.7%. Group 2 had a PR of 3.3%, an OR of 80.8%, and an OHSS risk of 13.3%. Group 3 had a PR of 6.7%, an OR of 92.6%, and an OHSS risk of 10%. The OR was significantly higher in the CC group than in the other groups (p=0.022). However, no significant differences were observed among groups in PR or OHSS risk (p>0.05).</p><p><strong>Conclusion: </strong>Adding a single dose of FA before or after CC did not improve treatment success in patients with unexplained infertility.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hoan Phuc Nguyen, Dung Ngoc Le, Hoa Thanh Nguyen, Thanh Huy Dao, Hoa Thi Le, Phuong Thi Thuy Dao, Son Khang Nguyen
{"title":"Comparative effectiveness of physiological intracytoplasmic sperm injection and intracytoplasmic sperm injection in couples affected by abnormal sperm morphology.","authors":"Hoan Phuc Nguyen, Dung Ngoc Le, Hoa Thanh Nguyen, Thanh Huy Dao, Hoa Thi Le, Phuong Thi Thuy Dao, Son Khang Nguyen","doi":"10.5653/cerm.2026.09579","DOIUrl":"https://doi.org/10.5653/cerm.2026.09579","url":null,"abstract":"<p><strong>Objective: </strong>This study compared outcomes after physiological intracytoplasmic sperm injection (PICSI) versus conventional intracytoplasmic sperm injection (ICSI) in couples affected by abnormal sperm morphology.</p><p><strong>Methods: </strong>This retrospective cohort study included 246 couples in whom the male partner had abnormal sperm morphology, defined as normal morphology <4% according to World Health Organization 2021 criteria, and who underwent assisted reproductive treatment at the in vitro fertilization and Tissue Engineering Center, Hanoi Medical University Hospital, from January 2022 to January 2024. Couples underwent either PICSI or conventional ICSI according to routine clinical practice. To reduce confounding, 1:1 matching based on female age, anti-Müllerian hormone level, and antral follicle count was performed. Embryological and clinical outcomes were compared between groups. Clinical outcomes were assessed only in first frozen embryo transfer cycles using day-5 blastocysts.</p><p><strong>Results: </strong>No significant differences were observed between the PICSI and ICSI groups in embryological outcomes, including the number of metaphase II oocytes, fertilization rate, day-5 blastocyst formation rate, and high-quality blastocyst rate. Clinical outcomes were also comparable, including the rates of positive serum beta-human chorionic gonadotropin, clinical pregnancy, implantation, ongoing pregnancy, pregnancy with multiple gestational sacs, and live birth. Subgroup analyses stratified by female and male age likewise showed no significant differences in outcomes.</p><p><strong>Conclusion: </strong>In this real-world Vietnamese cohort of couples affected by abnormal sperm morphology, PICSI demonstrated no significant advantage over conventional ICSI. These findings support individualized selection of sperm injection techniques rather than routine PICSI use. Future prospective studies incorporating sperm DNA fragmentation testing and sibling-oocyte designs are warranted.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mako Goto, Osamu Okitsu, Kohei Mizuno, Atsuko Kusuhara, Koji Kusuhara
{"title":"Humidified culture in a dry incubator improves culture performance.","authors":"Mako Goto, Osamu Okitsu, Kohei Mizuno, Atsuko Kusuhara, Koji Kusuhara","doi":"10.5653/cerm.2025.08844","DOIUrl":"https://doi.org/10.5653/cerm.2025.08844","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine whether localized humidification within a dry incubator could mitigate increased osmotic pressure in the culture medium and improve embryo development and clinical outcomes.</p><p><strong>Methods: </strong>In vitro culture and pregnancy outcomes were retrospectively compared between a dry incubator group (K-dry) and a conventional humidified incubator group (WJ). In addition, a K-humidified group was prospectively established by adding 4 mL of human tubal fluid medium outside the wells in a dry incubator to assess whether localized humidification improved outcomes compared with conventional dry conditions.</p><p><strong>Results: </strong>In the two-group comparison, the WJ group had significantly higher rates of good-morphology day 3 embryos, blastocyst formation, and good-morphology blastocysts than the K-dry group (p<0.05). In multivariate analysis, dry culture conditions were independently associated with poorer developmental outcomes. In the three-group comparison, the K-humidified group had a significantly higher rate of good-morphology day 3 embryos than the K-dry group (p=0.011) and did not differ significantly from the WJ group. Clinical pregnancy and ongoing pregnancy rates did not differ significantly across the study groups.</p><p><strong>Conclusion: </strong>Dry culture conditions may compromise embryo quality through osmotic stress. Localized humidification within a dry incubator was associated with improved early embryo development and increased the number of embryos suitable for transfer or cryopreservation, with comparable performance to a conventional humidified incubator. However, once embryos reached a transferable blastocyst stage, implantation potential appeared to be driven primarily by intrinsic embryo competence rather than by the prior culture environment.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between serum vitamin D status and early pregnancy outcomes in first in vitro fertilization cycles with high-quality embryo transfer.","authors":"Sol-Ee Yun, Jung-Jae Seo","doi":"10.5653/cerm.2026.09593","DOIUrl":"https://doi.org/10.5653/cerm.2026.09593","url":null,"abstract":"<p><strong>Objective: </strong>Vitamin D has been widely studied in assisted reproductive technology, but findings remain inconsistent. This study evaluated the association between serum vitamin D levels and early pregnancy outcomes in a strictly controlled cohort designed to minimize confounding.</p><p><strong>Methods: </strong>This retrospective cohort study included 129 women undergoing their first in vitro fertilization (IVF) cycle between 2023 and 2025 with transfer of at least 1 high-quality embryo. Patients were categorized according to serum vitamin D status as insufficient (<30 ng/mL) or sufficient (≥30 ng/mL). Multivariable logistic regression was adjusted for maternal age, anti-Müllerian hormone (AMH), embryo transfer day, and seasonal variation.</p><p><strong>Results: </strong>In the full cohort (n=129), clinical pregnancy rates were 54.5% (12/22) in the sufficient group and 33.6% (36/107) in the insufficient group (p=0.065). In the complete-case analysis (n=107) with available AMH data, the sufficient group had a higher clinical pregnancy rate than the insufficient group (63.2% [12/19] vs. 36.4% [32/88]; crude odds ratio [OR], 3.00; 95% confidence interval [CI], 1.07 to 8.39; p=0.036). However, in this analysis set, vitamin D sufficiency was not an independent predictor of clinical pregnancy (adjusted OR [aOR], 2.31; 95% CI, 0.77 to 6.98; p=0.137). Sensitivity analysis using a 20 ng/mL threshold showed no significant association (aOR, 1.21; 95% CI, 0.53 to 2.77; p=0.648). Maternal age remained the only statistically significant predictor (aOR, 0.89 per year; 95% CI, 0.79 to 1.00; p=0.041), even after seasonal adjustment.</p><p><strong>Conclusion: </strong>Serum vitamin D status was not independently associated with clinical pregnancy in this cohort. However, the wide CIs suggest that clinically relevant effects cannot be excluded. Previously reported positive associations may reflect residual confounding rather than direct biological effects, warranting larger prospective trials.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of intravenous remdesivir on endometrial receptivity in female mice.","authors":"Jamileh Sadat Mirsanei, Azam Govahi, Zahra Abroodi, Rana Mehdizadeh, Ronak Shabani, Mehdi Mehdizadeh, Marziyeh Ajdary","doi":"10.5653/cerm.2026.09138","DOIUrl":"10.5653/cerm.2026.09138","url":null,"abstract":"<p><strong>Objective: </strong>Pregnant women with coronavirus disease 2019 (COVID-19) are more likely than nonpregnant women to require admission to an intensive care unit, and many may require antiviral therapy. Remdesivir, an antiviral drug used to treat COVID-19, may exert toxic effects on specific tissues and organs. Therefore, this study investigated the effects of remdesivir on endometrial tissue in pregnant female mice.</p><p><strong>Methods: </strong>Thirty female Naval Medical Research Institute (NMRI) mice were divided into five groups. The control group received no treatment, and the sham group received the remdesivir solvent, dimethyl sulfoxide. The 2-, 4-, and 8-mg groups received the corresponding doses of remdesivir. Treatment continued for 10 days. After injection and mating, the presence of a vaginal plug was considered to indicate gestational day 1. On gestational day 4.5, uterine tissue damage, pinopode status, serum estradiol levels, and tissue expression of interleukin-6 and interleukin-1β were examined.</p><p><strong>Results: </strong>Serum estradiol levels and interleukin-6 expression in endometrial tissue decreased in a dose-dependent manner after remdesivir treatment. Remdesivir treatment was also associated with fewer uterine pinopodes and histological evidence of endometrial tissue injury (p<0.05).</p><p><strong>Conclusion: </strong>In pregnant mice, remdesivir reduced serum estradiol levels, decreased the number of endometrial pinopodes, and suppressed interleukin-6 expression. These findings suggest that remdesivir may adversely affect the endometrium and potentially compromise implantation; however, direct functional validation is required.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nahid Pashaie, Delsuz Rezaee, Sara Hosseini, Mohammad Salehi
{"title":"In vitro oocyte maturation is associated with altered OCT4 promoter methylation, DNMT expression, and early embryonic development in transgenic mouse embryos.","authors":"Nahid Pashaie, Delsuz Rezaee, Sara Hosseini, Mohammad Salehi","doi":"10.5653/cerm.2026.09152","DOIUrl":"https://doi.org/10.5653/cerm.2026.09152","url":null,"abstract":"<p><strong>Objective: </strong>In vitro oocyte maturation (IVM) is widely used in assisted reproductive technologies; however, its potential effects on epigenetic regulation and embryonic development remain incompletely understood. In this study, we compared the developmental competence and epigenetic characteristics of transgenic mouse embryos derived from in vitro-matured and in vivo-matured oocytes.</p><p><strong>Methods: </strong>A human OCT4-enhanced green fluorescent protein (EGFP) construct was microinjected into fertilized oocytes, and embryo development was evaluated by assessing cleavage and blastocyst formation rates. The methylation status of the OCT4 promoter was assessed using methylation-specific polymerase chain reaction (PCR), and the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l) and endogenous Oct4 were analyzed using quantitative real-time PCR.</p><p><strong>Results: </strong>Embryos derived from IVM oocytes exhibited significantly reduced cleavage and blastocyst formation rates compared with those derived from in vivo-matured oocytes. In addition, differences in OCT4 promoter methylation patterns and altered expression of DNMTs were observed between the two groups. In particular, increased Dnmt3a expression and decreased Oct4 expression were associated with embryos derived from IVM oocytes.</p><p><strong>Conclusion: </strong>These findings suggest that IVM is associated with epigenetic alterations that may influence early embryonic development and the quality of transgenic embryos. Improved understanding of these effects may contribute to the optimization of IVM protocols and outcomes in assisted reproductive technologies.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of environmentally relevant ibuprofen exposure on ovarian follicular atresia in Wistar rats: A biochemical and immunohistological study.","authors":"Safa Mouaki Benani, Souheyla Benbia, Yamina Belkhiri, Kahina Yahia, Angham Ouadah, Aya Chafai","doi":"10.5653/cerm.2025.09089","DOIUrl":"10.5653/cerm.2025.09089","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate whether chronic exposure to environmentally relevant concentrations of ibuprofen promotes follicular atresia in female rats and to explore potential underlying mechanisms affecting ovarian function.</p><p><strong>Methods: </strong>Ten adult female Wistar rats were randomly assigned to two groups (n=5 per group): a control group and an ibuprofen-exposed group. The experiment was conducted over a 4-month period. The control group received standard drinking water, whereas the ibuprofen group received drinking water supplemented with ibuprofen. Body weight and ovarian index were recorded throughout the study. Ovarian tissues were examined histologically to quantify atretic follicles and to assess structural alterations. Immunohistochemical analysis was performed to evaluate B-cell lymphoma 2 (Bcl-2) expression. Biochemical analyses were conducted to measure oxidative stress markers, including malondialdehyde and catalase, and serum levels of estradiol and interleukin 6 (IL-6) were determined.</p><p><strong>Results: </strong>Chronic ibuprofen exposure was associated with a significant increase in follicular atresia and induced marked histopathological alterations in ovarian tissue. Both body weight gain and the ovarian index were reduced in the ibuprofen group compared with controls. Biochemical analyses demonstrated elevated oxidative stress, along with disrupted serum estradiol and IL-6 levels. In addition, Bcl-2 expression was downregulated in ibuprofen-exposed rats.</p><p><strong>Conclusion: </strong>Even at environmentally relevant concentrations, ibuprofen exposure may compromise ovarian function by promoting follicular atresia through multiple interacting pathways, including oxidative stress, inflammatory responses, downregulation of Bcl-2, and impaired estradiol synthesis. These findings highlight the potential reproductive health risks associated with chronic low-dose environmental exposure to ibuprofen.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":"53 3","pages":"298-306"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elmira Sayad, Masoumeh Faghani, Parvaneh Keshavarz, Ali Rafiei, Fahimeh Mohammadghasemi
{"title":"Quercetin attenuates nicotine-induced ovarian and uterine dysfunction in rats.","authors":"Elmira Sayad, Masoumeh Faghani, Parvaneh Keshavarz, Ali Rafiei, Fahimeh Mohammadghasemi","doi":"10.5653/cerm.2025.08298","DOIUrl":"10.5653/cerm.2025.08298","url":null,"abstract":"<p><strong>Objective: </strong>Nicotine, a principal constituent of tobacco smoke, disrupts female reproductive physiology. Quercetin, a flavonoid with both phytoestrogenic and antioxidant properties, may counteract this toxicity. This study aimed to evaluate the histological, biochemical, and molecular effects of quercetin co-administration with nicotine on ovarian and uterine tissues in rats.</p><p><strong>Methods: </strong>Thirty-two female Wistar rats were assigned to four groups: control, nicotine-treated (1 mg/kg), quercetin-treated (15 mg/kg), and a combined nicotine (1 mg/kg)-quercetin (15 mg/kg) group. Histopathological assessments were performed alongside biochemical analyses of oxidative stress markers-malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAC)-and enzyme-linked immunosorbent assay (ELISA)-based hormonal profiling. Immunohistochemistry was employed to quantify estrogen receptor-alpha (ERα) and Ki-67 expression.</p><p><strong>Results: </strong>Co-administration of nicotine and quercetin increased uterine wall thickness and was associated with elevated estradiol levels, reduced MDA activity, and increased SOD and TAC in both uterine and ovarian tissues compared with the nicotine group. The nicotine-quercetin group also showed a lower Ki-67 index in ovarian follicles and stroma, along with a marked reduction in atretic follicles. Conversely, there were significant increases in antral follicles, corpus luteum formation, and ERα expression in the uterine endometrium and epithelium, as well as in the ovarian stroma and corpus luteum, versus the nicotine-only group.</p><p><strong>Conclusion: </strong>Quercetin (15 mg/kg) appears to protect against nicotine-induced reproductive impairments (1 mg/kg), likely through its antioxidant properties, its capacity to stabilize hormone levels, and its modulation of ERα and Ki-67 expression. These findings support quercetin's therapeutic potential for preventing or alleviating smoking-related reproductive damage.</p>","PeriodicalId":46409,"journal":{"name":"Clinical and Experimental Reproductive Medicine-CERM","volume":" ","pages":"258-269"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}