Prenatal exposure to a mixture of phthalates accelerates the age-related decline in reproductive capacity but may not affect direct biomarkers of ovarian aging in the F1 generation of female mice.
Prenatal exposure to a mixture of phthalates accelerates the age-related decline in reproductive capacity but may not affect direct biomarkers of ovarian aging in the F1 generation of female mice.
复制标题
DOI：
10.1093/eep/dvab010
复制
发表时间：
2021
影响因子：
3.8
通讯作者：
Flaws JA
中科院分区：
文献类型：
--
作者：
Brehm E;Flaws JA
邻苯二甲酸酯用于许多消费品，导致人类每天接触。虽然许多研究集中在单一的邻苯二甲酸酯，人类暴露于邻苯二甲酸酯的混合物。我们的实验室创造了一种由六种不同邻苯二甲酸酯组成的邻苯二甲酸酯混合物，发现它对女性生殖产生负面影响，并加速了生殖衰老的一些生物标志物。然而，尚不清楚产前暴露于混合物是否会加速小鼠生殖能力和卵巢老化的自然下降。因此，我们检验了产前暴露于邻苯二甲酸酯混合物加速F1代小鼠生殖能力和卵巢衰老生物标志物年龄相关性下降的假设。妊娠CD-1母兽从妊娠第10天至出生每天经口给予对照品或邻苯二甲酸酯混合物（20 µg/kg/天-200 mg/kg/天）。将F1代雌性幼仔龄定为11-13月龄，然后在11和13月龄进行发情周期和繁殖试验。在13个月时从F1雌性收集卵巢以检查卵巢老化的生物标志物。与对照组相比，产前暴露于邻苯二甲酸酯混合物减少了F1雌性动物在发情前期的时间以及F1雌性动物在11和13月龄时分娩的能力。相反，产前暴露于混合物并不影响F1代卵巢直接老化的生物标志物。总的来说，我们的数据表明，产前邻苯二甲酸酯混合物暴露加速了与年龄相关的自然生殖能力下降，但可能不会影响F1代卵巢衰老的一些生物标志物。
Phthalates are used in many consumer products, leading to daily human exposure. Although many studies focus on single phthalates, humans are exposed to mixtures of phthalates. Our laboratory created a phthalate mixture consisting of six different phthalates and found that it negatively affected female reproduction and accelerated some biomarkers of reproductive aging. However, it was unknown if prenatal exposure to the mixture accelerates the natural decline in reproductive capacity and ovarian aging in mice. Therefore, we tested the hypothesis that prenatal exposure to a phthalate mixture accelerates the age-related decline in reproductive capacity and biomarkers of ovarian aging in the F1 generation of mice. Pregnant CD-1 dams were orally dosed with control or phthalate mixture (20 µg/kg/day–200 mg/kg/day) daily from gestational day 10—birth. The F1 female pups were aged to 11–13 months, and then estrous cyclicity and breeding trials were conducted at 11 and 13 months. Ovaries were collected from the F1 females at 13 months to examine biomarkers of ovarian aging. Prenatal exposure to the phthalate mixture decreased the time the F1 females spent in proestrus and the ability of the F1 females to give birth at 11 and 13 months of age compared to control. In contrast, prenatal exposure to the mixture did not affect biomarkers of direct aging of the ovary in the F1 generation. Collectively, our data show that prenatal phthalate mixture exposure accelerates the natural age-related decline in reproductive capacity but may not affect some biomarkers of ovarian aging in the F1 generation.