Prenatal exposure to an environmentally relevant phthalate mixture accelerates biomarkers of reproductive aging in a multiple and transgenerational manner in female mice.
Prenatal exposure to an environmentally relevant phthalate mixture accelerates biomarkers of reproductive aging in a multiple and transgenerational manner in female mice.
复制标题
DOI：
10.1016/j.reprotox.2020.10.009
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Flaws JA
中科院分区：
文献类型：
--
作者：
Brehm E;Zhou C;Gao L;Flaws JA
邻苯二甲酸酯是已知的内分泌干扰化学品，存在于许多消费品中。我们的实验室以前开发了一种由六种邻苯二甲酸酯组成的相关邻苯二甲酸酯混合物，发现它会破坏小鼠的雌性生育能力。然而，尚不清楚产前暴露于邻苯二甲酸酯混合物是否会加速生殖老化，以及这种情况是否会发生在多代人中。因此，我们测试了产前暴露于邻苯二甲酸酯混合物加速多代雌性小鼠生殖衰老生物标志物的假设。妊娠CD-1小鼠从妊娠第10天至出生每天经口给予溶剂对照或邻苯二甲酸酯混合物（20μg/kg/天-500 mg/kg/天）。将这些母鼠所产的成年F1雌性动物与未暴露的雄性动物交配，以产生F2和F3代。在13个月时，监测发情周期，并收集卵巢和血清进行分析。在F1代中，与对照组相比，混合物降低了睾酮和睾酮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，邻苯二甲酸酯混合物降低了窦卵泡百分比和睾酮激素水平。在F3代，产前暴露于邻苯二甲酸酯混合物增加卵巢重量，增加发情后期/间情期的时间，改变卵泡数量，并降低促黄体激素水平相比，控制。总的来说，这些数据表明，产前暴露于邻苯二甲酸酯混合物可能会加速生殖衰老的几个生物标志物在一个多代和跨代的方式在雌性小鼠。
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 (20μg/kg/day-500mg/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.
登录
查看更多内容
影响因子：
--
作者：
Guillaumet-Adkins A;Yañez Y;Peris-Diaz MD;Calabria I;Palanca-Ballester C;Sandoval J
通讯作者：
Sandoval J
影响因子：
3.4
作者：
Babich, MA;Chen, SB;Zamula, WW
通讯作者：
Zamula, WW
影响因子：
3.8
作者：
Chiang, Catheryne;Flaws, Jodi A.
通讯作者：
Flaws, Jodi A.
影响因子：
3.6
作者：
Braun JM;Sathyanarayana S;Hauser R
通讯作者：
Hauser R
影响因子：
3.3
作者：
Gallavan, RH;Holson, JF;Reynolds, VL
通讯作者：
Reynolds, VL