Phthalates are known endocrine-disrupting chemicals that are found in many consumer products. Our laboratory previously developed a relevant phthalate mixture consisting of six phthalates and found that it disrupted female fertility in mice. However, it is unknown if prenatal exposure to phthalate mixtures can accelerate reproductive aging and if this occurs in multiple generations. Thus, we tested the hypothesis that prenatal exposure to a mixture of phthalates accelerates biomarkers of reproductive aging in multiple generations of female mice. Pregnant CD-1 mice were orally dosed with vehicle control or a phthalate mixture (20 µg/kg/day-500 mg/kg/day) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to create the F2 and F3 generations by mating them with unexposed males. At 13 months, estrous cyclicity was monitored and ovaries and sera were collected for analysis. In the F1 generation, the mixture decreased testosterone and inhibin B levels, but increased follicle-stimulating hormone and luteinizing hormone levels compared to control. In the F2 generation, the phthalate mixture decreased the percent of antral follicles and testosterone hormone levels compared to control. In the F3 generation, prenatal exposure to the phthalate mixture increased ovarian weight, increased the time in metestrus/diestrus, altered follicle numbers, and decreased the levels of luteinizing hormone compared to control. Collectively, these data suggest that prenatal exposure to a phthalate mixture may accelerate several biomarkers of reproductive aging in a multi- and transgenerational manner in female mice.

邻苯二甲酸盐是已知的内分泌干扰化学物质，存在于许多消费品中。我们的实验室之前开发了一种由六种邻苯二甲酸盐组成的相关邻苯二甲酸盐混合物，发现它会破坏雌性小鼠的生育能力。然而，尚不清楚产前接触邻苯二甲酸酯混合物是否会加速生殖衰老，以及这种情况是否会在多代中发生。因此，我们测试了这样的假设：产前接触邻苯二甲酸盐混合物会加速多代雌性小鼠生殖衰老的生物标志物。从妊娠第 10 天到出生，怀孕的 CD-1 小鼠每天口服载体对照或邻苯二甲酸酯混合物（20 µg/kg/天-500 mg/kg/天）。这些水坝所生的成年 F1 雌性被用来与未暴露的雄性交配，产生 F2 和 F3 代。13 个月时，监测动情周期并收集卵巢和血清进行分析。在 F1 代中，与对照组相比，该混合物降低了睾酮和抑制素 B 水平，但增加了卵泡刺激素和黄体生成素水平。在 F2 代中，与对照组相比，邻苯二甲酸盐混合物降低了窦卵泡的百分比和睾酮激素水平。在 F3 代中，与对照组相比，产前接触邻苯二甲酸酯混合物会增加卵巢重量，增加发情后期/间期时间，改变卵泡数量，并降低促黄体激素水平。总的来说，这些数据表明，产前接触邻苯二甲酸盐混合物可能会以多代和跨代的方式加速雌性小鼠生殖衰老的几个生物标志物。