Data_Sheet_1_In utero Exposure to Excessive Estrogen Impairs Homologous Recombination and Oogenesis via Estrogen Receptor 2 in Mice.docx

The association between the accumulation of synthetic chemicals with estrogenic activity and risks to oogenesis has become a growing concern. This study indicates that in utero estrogen exposure can affect homologous recombination in early oogenesis and influence the reproductive potential and lifespan of female offspring. We conducted this study in developing mouse ovaries using two different models: oral doses administered to the mother, and fetal ovary cultures. Our analyses of meiotic fetal oocytes suggest that 17-β-estradiol induces gross aberrations in prophase I events, including delayed meiotic progression, increased unrepaired DNA damage, and altered homologous recombination levels. These effects were mainly mediated by estrogen receptor 2 (ESR2) activation. Mid-gestation exposure to estrogen also led to delayed primordial folliculogenesis after birth, impaired follicle development after prepuberty, and ultimately reduced the total litter size of the offspring. This raises the concern that maternal exposures to substances activating ESR2 may compromise the fertility of the exposed female fetus.

具有雌激素活性的合成化学物蓄积与卵子发生风险之间的关联已日益受到学界关注。本研究发现，子宫内雌激素暴露可影响早期卵子发生过程中的同源重组，并影响雌性子代的生殖潜能与寿命。本研究以发育中的小鼠卵巢为实验对象，采用两种研究模型：对母鼠经口给药，以及胎鼠卵巢体外培养。针对减数分裂期胎鼠卵母细胞的分析结果显示，17β-雌二醇（17-β-estradiol）可诱导减数分裂I期前期事件出现显著异常，具体包括减数分裂进程延迟、未修复DNA损伤增多以及同源重组水平改变。上述效应主要通过激活雌激素受体2（ESR2）介导。妊娠中期的雌激素暴露还会导致子代出生后原始卵泡发生延迟，青春期后卵泡发育受损，并最终降低子代的每胎总产仔数。这一结果引发了学界的担忧：母体暴露于可激活ESR2的物质，可能会损害暴露雌性胎儿的生育能力。