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孕期暴露于环境相关的邻苯二甲酸酯混合物以多种跨代方式加速雌性小鼠生殖衰老的生物标志物。

Prenatal exposure to an environmentally relevant phthalate mixture accelerates biomarkers of reproductive aging in a multiple and transgenerational manner in female mice.

机构信息

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States.

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States.

出版信息

Reprod Toxicol. 2020 Dec;98:260-268. doi: 10.1016/j.reprotox.2020.10.009. Epub 2020 Oct 28.

Abstract

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.

摘要

邻苯二甲酸酯是已知的内分泌干扰化学物质,存在于许多消费产品中。我们实验室之前开发了一种含有六种邻苯二甲酸酯的相关邻苯二甲酸酯混合物,并发现它会破坏小鼠的雌性生育能力。然而,目前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衰老,以及这种情况是否会在多个世代中发生。因此,我们检验了这样一个假设,即产前暴露于邻苯二甲酸酯混合物会加速雌性小鼠多个世代生殖衰老的生物标志物。从妊娠第 10 天到出生,用含有邻苯二甲酸酯混合物(20μg/kg/天-500mg/kg/天)的溶液或载体溶液每天对 CD-1 孕鼠进行经口灌胃处理。这些母鼠所生的 F1 雌性后代与未暴露的雄性交配,用于产生 F2 和 F3 代。在 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,混合物降低了睾酮和抑制素 B 的水平,但增加了卵泡刺激素和黄体生成素的水平。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的比例和睾酮激素水平。在 F3 代中,与对照组相比,产前暴露于邻苯二甲酸酯混合物增加了卵巢重量,增加了间情期/发情期的时间,改变了卵泡数量,并降低了黄体生成素的水平。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以多代和跨代的方式加速雌性小鼠的几个生殖衰老的生物标志物。

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