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外源性雌激素对发育中性腺细胞命运决定的影响:人类生殖健康下降的潜在原因。

Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health.

机构信息

School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia.

出版信息

Int J Mol Sci. 2020 Nov 8;21(21):8377. doi: 10.3390/ijms21218377.

Abstract

The increasing incidence of testicular dysgenesis syndrome-related conditions and overall decline in human fertility has been linked to the prevalence of oestrogenic endocrine disrupting chemicals (EDCs) in the environment. Ectopic activation of oestrogen signalling by EDCs in the gonad can impact testis and ovary function and development. Oestrogen is the critical driver of ovarian differentiation in non-mammalian vertebrates, and in its absence a testis will form. In contrast, oestrogen is not required for mammalian ovarian differentiation, but it is essential for its maintenance, illustrating it is necessary for reinforcing ovarian fate. Interestingly, exposure of the bi-potential gonad to exogenous oestrogen can cause XY sex reversal in marsupials and this is mediated by the cytoplasmic retention of the testis-determining factor SOX9 (sex-determining region Y box transcription factor 9). Oestrogen can similarly suppress SOX9 and activate ovarian genes in both humans and mice, demonstrating it plays an essential role in all mammals in mediating gonad somatic cell fate. Here, we review the molecular control of gonad differentiation and explore the mechanisms through which exogenous oestrogen can influence somatic cell fate to disrupt gonad development and function. Understanding these mechanisms is essential for defining the effects of oestrogenic EDCs on the developing gonads and ultimately their impacts on human reproductive health.

摘要

睾丸发育不良综合征相关疾病的发病率不断上升和人类生育能力的整体下降与环境中雌激素类内分泌干扰化学物质(EDCs)的流行有关。EDCs 在性腺中的雌激素信号的异位激活会影响睾丸和卵巢的功能和发育。雌激素是脊椎动物中非哺乳动物卵巢分化的关键驱动因素,在没有雌激素的情况下会形成睾丸。相比之下,雌激素对于哺乳动物卵巢的分化不是必需的,但对于其维持是必需的,这表明它对于加强卵巢命运是必要的。有趣的是,外源性雌激素暴露于双潜能性腺会导致有袋动物的 XY 性别反转,这是由睾丸决定因子 SOX9(性别决定区 Y 框转录因子 9)的细胞质保留介导的。雌激素可以类似地抑制人和小鼠中的 SOX9 并激活卵巢基因,表明它在所有哺乳动物中都发挥着重要作用,在介导性腺体细胞命运中发挥作用。在这里,我们回顾了性腺分化的分子控制,并探讨了外源性雌激素影响体细胞命运以破坏性腺发育和功能的机制。了解这些机制对于确定雌激素类 EDCs 对发育中性腺的影响以及它们对人类生殖健康的最终影响至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9853/7664701/ea45a6f703b9/ijms-21-08377-g001.jpg

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