E E Lara-Molina, V Garrigós, A Vázquez, D Amorós, M Florensa, X Tao, A Ballesteros, A Chisvert, R González-Martín, F Dominguez
{"title":"P-628 Bisphenol exposure and its impact on telomere length and ovarian reserve in reproductive-age women","authors":"E E Lara-Molina, V Garrigós, A Vázquez, D Amorós, M Florensa, X Tao, A Ballesteros, A Chisvert, R González-Martín, F Dominguez","doi":"10.1093/humrep/deaf097.934","DOIUrl":null,"url":null,"abstract":"Study question Do concentrations of bisphenols (BPs) in follicular fluid (FF), serum, and urine influence telomere length (TL) in leukocytes and cumulus cells of reproductive-age women? Summary answer Higher concentrations of BPs in FF and urine are associated with leukocyte telomere shortening and reduced antral follicle count. What is known already Exposure to BPs, primarily present in plastics, adversely affects oocyte quality and female fertility. Elevated urinary BP levels are associated with meiotic cell cycle arrest, abnormal meiotic spindle formation, chromosomal misalignment, reduced antral follicle counts, and diminished oocyte yield in IVF patients. However, the specific mechanisms affecting oocyte health remain unclear. In vitro studies show BP exposure inhibits telomerase activity and shortens telomeres in leukocytes; yet its effects on TL in ovarian follicle cells, and consequently on female reproductive aging, remain unstudied. Study design, size, duration This prospective, non-interventional cohort study included 134 egg donors who underwent controlled ovarian stimulation following the clinic’s standard protocol. On the day of vaginal oocyte retrieval, samples of blood (leukocytes and plasma), urine, FF, and cumulus cells were collected. Relative TL was measured in leukocytes (LTL) and cumulus cells (CCTL). Additionally, nine bisphenols (BPA, BPAP, BPAF, BPB, BPC, BPE, BPF, BPS, and BPZ) were quantified in serum, urine, and FF samples. Participants/materials, setting, methods The nine BPs were analyzed using a miniaturized sorptive dispersive microextraction method. Genomic DNA from leukocytes and cumulus cells was isolated for TL measurements. Relative TL was assessed using a SYBR-Green real-time quantitative PCR protocol. Generalized linear models examined associations between bisphenols, TLs, antral follicle count (AFC), anti-müllerian hormone (AMH), and mature oocytes, estimating mean differences per dose-2fold increase (95% CI). Crude and age-BMI-smoking-adjusted models were applied. Main results and the role of chance Participants had a median age of 25 years [IQR: 21–28] and a BMI of 22.51 kg/m² [IQR: 20.76–24.43]; 45.5% had never smoked. Among the nine BPs evaluated in three biological matrices, only BPA and BPE in FF, and BPZ and BPF in urine, were detected in at least 50% of participants and included in further analysis. The sum of BPs in each biofluid was calculated as a new exposure variable. Mean and interquartile range BP concentrations (ng/mL) were as follows: FF-BPA 1.67 [0.10–5.37], FF-BPE 0.00 [0.00–0.11], FF-∑BP 1.84 [0.11–5.42], U-BPF 0.02 [0.01–0.09], U-BPZ 0.03 [0.00–0.08], and U-∑BP 0.09 [0.03–0.20]. No correlations were observed among biofluids for any bisphenol. In the adjusted models, CCTL was not significantly affected by any bisphenols. However, higher FF-∑BP concentrations were associated with a significant 1% decrease in LTL [0.99 (0.99–1.00), p = 0.023]. Higher urinary BPZ concentrations were significantly associated with reduced antral follicle count [0.98 (0.97–1.00), p = 0.012], though AMH levels showed no significant associations with BP concentrations. Regarding mature oocytes obtained, no significant associations were observed for any evaluated BPs. Limitations, reasons for caution Further research is required to confirm the association between detectable BP concentrations in biological fluids and reproductive aging, as well as diminished reproductive outcomes in women. Such studies should include larger populations and longitudinal assessments across multiple time points to provide more robust and comprehensive evidence. Wider implications of the findings Exposure to BPs may significantly influence telomere length and ovarian reserve. Evaluating multiple BPs and other plasticizers is essential to understanding their harmful effects on ovarian aging and reproductive outcomes. Their environmental ubiquity raises serious concerns about long-term ecological and health impacts, highlighting the need for comprehensive research and regulation. Trial registration number No","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"2 1","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human reproduction","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/humrep/deaf097.934","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Study question Do concentrations of bisphenols (BPs) in follicular fluid (FF), serum, and urine influence telomere length (TL) in leukocytes and cumulus cells of reproductive-age women? Summary answer Higher concentrations of BPs in FF and urine are associated with leukocyte telomere shortening and reduced antral follicle count. What is known already Exposure to BPs, primarily present in plastics, adversely affects oocyte quality and female fertility. Elevated urinary BP levels are associated with meiotic cell cycle arrest, abnormal meiotic spindle formation, chromosomal misalignment, reduced antral follicle counts, and diminished oocyte yield in IVF patients. However, the specific mechanisms affecting oocyte health remain unclear. In vitro studies show BP exposure inhibits telomerase activity and shortens telomeres in leukocytes; yet its effects on TL in ovarian follicle cells, and consequently on female reproductive aging, remain unstudied. Study design, size, duration This prospective, non-interventional cohort study included 134 egg donors who underwent controlled ovarian stimulation following the clinic’s standard protocol. On the day of vaginal oocyte retrieval, samples of blood (leukocytes and plasma), urine, FF, and cumulus cells were collected. Relative TL was measured in leukocytes (LTL) and cumulus cells (CCTL). Additionally, nine bisphenols (BPA, BPAP, BPAF, BPB, BPC, BPE, BPF, BPS, and BPZ) were quantified in serum, urine, and FF samples. Participants/materials, setting, methods The nine BPs were analyzed using a miniaturized sorptive dispersive microextraction method. Genomic DNA from leukocytes and cumulus cells was isolated for TL measurements. Relative TL was assessed using a SYBR-Green real-time quantitative PCR protocol. Generalized linear models examined associations between bisphenols, TLs, antral follicle count (AFC), anti-müllerian hormone (AMH), and mature oocytes, estimating mean differences per dose-2fold increase (95% CI). Crude and age-BMI-smoking-adjusted models were applied. Main results and the role of chance Participants had a median age of 25 years [IQR: 21–28] and a BMI of 22.51 kg/m² [IQR: 20.76–24.43]; 45.5% had never smoked. Among the nine BPs evaluated in three biological matrices, only BPA and BPE in FF, and BPZ and BPF in urine, were detected in at least 50% of participants and included in further analysis. The sum of BPs in each biofluid was calculated as a new exposure variable. Mean and interquartile range BP concentrations (ng/mL) were as follows: FF-BPA 1.67 [0.10–5.37], FF-BPE 0.00 [0.00–0.11], FF-∑BP 1.84 [0.11–5.42], U-BPF 0.02 [0.01–0.09], U-BPZ 0.03 [0.00–0.08], and U-∑BP 0.09 [0.03–0.20]. No correlations were observed among biofluids for any bisphenol. In the adjusted models, CCTL was not significantly affected by any bisphenols. However, higher FF-∑BP concentrations were associated with a significant 1% decrease in LTL [0.99 (0.99–1.00), p = 0.023]. Higher urinary BPZ concentrations were significantly associated with reduced antral follicle count [0.98 (0.97–1.00), p = 0.012], though AMH levels showed no significant associations with BP concentrations. Regarding mature oocytes obtained, no significant associations were observed for any evaluated BPs. Limitations, reasons for caution Further research is required to confirm the association between detectable BP concentrations in biological fluids and reproductive aging, as well as diminished reproductive outcomes in women. Such studies should include larger populations and longitudinal assessments across multiple time points to provide more robust and comprehensive evidence. Wider implications of the findings Exposure to BPs may significantly influence telomere length and ovarian reserve. Evaluating multiple BPs and other plasticizers is essential to understanding their harmful effects on ovarian aging and reproductive outcomes. Their environmental ubiquity raises serious concerns about long-term ecological and health impacts, highlighting the need for comprehensive research and regulation. Trial registration number No
期刊介绍:
Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues.
Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.