P-628 Bisphenol exposure and its impact on telomere length and ovarian reserve in reproductive-age women

IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
E E Lara-Molina, V Garrigós, A Vázquez, D Amorós, M Florensa, X Tao, A Ballesteros, A Chisvert, R González-Martín, F Dominguez
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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
双酚暴露及其对育龄妇女端粒长度和卵巢储备的影响
研究问题卵泡液(FF)、血清和尿液中的双酚(bp)浓度是否影响育龄妇女白细胞和积云细胞的端粒长度(TL) ?FF和尿液中较高浓度的bp与白细胞端粒缩短和窦泡计数减少有关。暴露于主要存在于塑料中的bp会对卵母细胞质量和女性生育能力产生不利影响。在体外受精患者中,尿血压水平升高与减数分裂细胞周期停滞、减数分裂纺锤体形成异常、染色体排列失调、窦卵泡计数减少和卵母细胞产量减少有关。然而,影响卵母细胞健康的具体机制尚不清楚。体外研究表明,BP暴露抑制端粒酶活性并缩短白细胞端粒;但其对卵巢卵泡细胞TL的影响,以及由此对女性生殖衰老的影响,仍未得到研究。这项前瞻性、非干预性队列研究包括134名卵子捐赠者,他们按照临床标准方案接受了受控的卵巢刺激。取阴道卵母细胞当天,采集血液(白细胞和血浆)、尿液、FF和积云细胞样本。测定白细胞(LTL)和积云细胞(CCTL)的相对TL。此外,测定了血清、尿液和FF样品中的9种双酚类物质(BPA、BPAP、BPAF、BPB、BPC、BPE、BPF、BPS和BPZ)。采用微型吸附分散微萃取法对9种bp进行分析。从白细胞和积云细胞中分离基因组DNA用于TL测量。采用SYBR-Green实时定量PCR技术评估相对TL。广义线性模型检验了双酚、TLs、窦卵泡计数(AFC)、抗勒氏杆菌激素(AMH)和成熟卵母细胞之间的关系,估计了每剂量增加2倍的平均差异(95% CI)。采用粗模型和年龄- bmi吸烟调整模型。参与者的中位年龄为25岁[IQR: 21-28], BMI为22.51 kg/m²[IQR: 20.76-24.43];45.5%的人从不吸烟。在三种生物基质中评估的9种bp中,只有FF中的BPA和BPE以及尿液中的BPZ和BPF在至少50%的参与者中被检测到,并被纳入进一步的分析。计算每种生物液中bp的总和作为一个新的暴露变量。平均BP浓度(ng/mL)为: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], U-∑BP 0.09[0.03 - 0.20]。在生物体液中没有观察到任何双酚的相关性。在调整后的模型中,CCTL不受任何双酚类物质的显著影响。而FF-∑BP浓度越高,LTL降低1% [0.99 (0.99 - 1.00),p = 0.023]。尿BPZ浓度升高与窦卵泡计数降低显著相关[0.98 (0.97-1.00),p = 0.012],但AMH水平与BP浓度无显著相关性。对于获得的成熟卵母细胞,没有观察到任何评估bp的显著关联。局限性,谨慎的原因需要进一步的研究来证实生物体液中可检测到的BP浓度与生殖老化以及女性生殖结果下降之间的联系。此类研究应包括更大的人群和跨多个时间点的纵向评估,以提供更有力和全面的证据。暴露于bp可能会显著影响端粒长度和卵巢储备。评估多种bp和其他增塑剂对于了解它们对卵巢老化和生殖结果的有害影响至关重要。它们在环境中的普遍存在引起了对长期生态和健康影响的严重关切,突出了全面研究和监管的必要性。试验注册号
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来源期刊
Human reproduction
Human reproduction 医学-妇产科学
CiteScore
10.90
自引率
6.60%
发文量
1369
审稿时长
1 months
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.
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