Wang Zifan, Fleisch Abby, Rifas-Shiman Sheryl L, Calafat Antonia M, James-Todd Tamarra, Coull Brent A, Chavarro Jorge E, Hivert Marie-France, Whooten Rachel C, Perng Wei, Oken Emily, Mahalingaiah Shruthi
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Center for Interdisciplinary Population and Health Research, MaineHealth Institute for Research, Westbrook, ME, USA; Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA.
Environ Res. 2025 Mar 1;268:120786. doi: 10.1016/j.envres.2025.120786. Epub 2025 Jan 9.
Per- and polyfluoroalkyl substances (PFAS) may impact ovarian folliculogenesis and steroidogenesis, but whether prenatal exposure may impact offspring reproductive health is unknown. This study examines the extent to which maternal PFAS plasma concentrations during pregnancy are associated with polycystic ovary syndrome (PCOS) and related characteristics in female offspring.
We studied 322 mother-daughter pairs in Project Viva, a Boston-area longitudinal pre-birth cohort enrolled 1999-2002. We examined associations of maternal prenatal (median: 9.6 weeks gestation) plasma concentrations of six PFAS (log2 transformed) with PCOS and related characteristics among daughters during mid-to-late adolescence. We estimated the associations of single PFAS and PFAS as a mixture with each outcome, using logistic regression and quantile g-computation, respectively, adjusting for parity, and maternal sociodemographic and other lifestyle/health factors.
Among the 322 mother-daughter pairs, the majority of mothers identified as non-Hispanic White and had a college degree, and 13% of daughters had either self-reported PCOS or probable PCOS based on irregular menstrual cycles and clinical or biochemical markers of hyperandrogenism. Among all daughters, there were 27% with irregular menstrual cycles, 34% with hirsutism, and 6% with moderate-to-severe acne. When fully adjusted for confounders, per doubling of maternal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) concentration was associated with higher odds of self-reported PCOS [OR (95% CI) = 2.66 (1.18, 5.99)], and per doubling of maternal perfluorononanoate (PFNA) concentration was associated with higher odds of moderate-to-severe acne [OR (95% CI) = 2.33 (1.09, 4.99)] in daughters with or without irregular menstrual cycles. We found no associations of the mixture of six PFAS with PCOS or related traits.
Our findings suggest a positive association between maternal concentrations of EtFOSAA and PCOS in their daughters during mid-to-late adolescence, although future studies with larger sample size and extended follow-up across the reproductive life-course are needed.
全氟和多氟烷基物质(PFAS)可能会影响卵巢卵泡生成和类固醇生成,但产前暴露是否会影响后代生殖健康尚不清楚。本研究调查了孕期母亲血浆中PFAS浓度与女性后代多囊卵巢综合征(PCOS)及相关特征之间的关联程度。
我们在“活力计划”中研究了322对母女,该计划是一个位于波士顿地区的纵向出生前队列,于1999年至2002年招募。我们研究了母亲产前(中位数:妊娠9.6周)血浆中六种PFAS(对数2转换后)的浓度与青春期中后期女儿的PCOS及相关特征之间的关联。我们分别使用逻辑回归和分位数g计算法,对单种PFAS以及PFAS混合物与每种结局的关联进行了估计,并对胎次、母亲的社会人口学特征以及其他生活方式/健康因素进行了调整。
在这322对母女中,大多数母亲为非西班牙裔白人且拥有大学学位,13%的女儿根据月经周期不规律以及高雄激素血症的临床或生化指标,自我报告患有PCOS或可能患有PCOS。在所有女儿中,27%月经周期不规律,34%多毛,6%患有中度至重度痤疮。在对混杂因素进行充分调整后,母亲2-(N-乙基全氟辛烷磺酰胺基)乙酸酯(EtFOSAA)浓度每增加一倍,与自我报告的PCOS几率较高相关[比值比(95%置信区间)=2.66(1.18,5.99)],母亲全氟壬酸(PFNA)浓度每增加一倍,与有或没有月经周期不规律的女儿中度至重度痤疮几率较高相关[比值比(95%置信区间)=2.33(1.09,4.99)]。我们发现六种PFAS混合物与PCOS或相关特征之间无关联。
我们的研究结果表明,母亲EtFOSAA浓度与青春期中后期女儿的PCOS之间存在正相关,不过未来需要开展样本量更大且涵盖整个生殖生命历程的长期随访研究。