Fetal programming of polycystic ovary syndrome: Effects of androgen exposure on prenatal ovarian development.
Fetal programming of polycystic ovary syndrome: Effects of androgen exposure on prenatal ovarian development.
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多囊卵巢综合征的胎儿编程：雄激素暴露对产前卵巢发育的影响。
DOI：
10.1016/j.jsbmb.2021.105830
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Blesson CS
中科院分区：
文献类型：
--
作者：
Barsky M;Merkison J;Hosseinzadeh P;Yang L;Bruno-Gaston J;Dunn J;Gibbons W;Blesson CS
多囊卵巢综合征（polycystic ovary syndrome，PCOS）是一种常见的无排卵性不孕症，具有很强的遗传成分，但尚未发现候选基因，其遗传方式可能是由于子宫内雄激素对基因表达和线粒体的编程所致。线粒体是母系遗传的，胎儿雄激素暴露后线粒体的改变可能是PCOS胎儿编程的机制之一。我们的目的是通过确定高雄激素血症如何影响新生儿卵巢中的基因表达和线粒体来研究产前过量雄激素在卵巢发育中的作用。妊娠母鼠在妊娠第16-18天注射双氢睾酮。收集第0天卵巢用于基因表达和线粒体研究。RNAseq显示与线粒体功能障碍、胎儿性腺发育、卵母细胞成熟、代谢、血管生成和PCOS相关的差异基因表达。前20个上调和下调的基因用qPCR和蛋白质印迹验证。参与卵泡发生的转录途径和参与卵巢和线粒体功能的基因失调。此外，DHT暴露改变线粒体超微结构和功能，增加线粒体耗氧量和线粒体效率降低，质子泄漏增加的第一天内的生活。我们的数据表明，导致PCOS的一条途径始于出生，并在子宫内由雄激素编程。
Polycystic ovary syndrome (PCOS) is a common form of anovulatory infertility with a strong hereditary component but no candidate genes have been found. The inheritance pattern may be due to in utero androgen programming on gene expression and mitochondria. Mitochondria are maternally inherited and alterations to mitochondria after fetal androgen exposure may explain one of the mechanisms of fetal programming in PCOS. Our aim was to investigate the role of excessive prenatal androgens in ovarian development by identifying how hyperandrogenemia affects gene expression and mitochondria in neonatal ovary. Pregnant dams were injected with dihydrotestosterone on days 16–18 of pregnancy. Day 0 ovaries were collected for gene expression and mitochondrial studies. RNAseq showed differential gene expressions which were related to mitochondrial dysfunction, fetal gonadal development, oocyte maturation, metabolism, angiogenesis, and PCOS. Top 20 up and downregulated genes were validated with qPCR and Western Blot. Transcriptional pathways involved in folliculogenesis and genes involved in ovarian and mitochondrial function were dysregulated. Further, DHT exposure altered mitochondrial ultrastructure and function by increasing mitochondrial oxygen consumption and decreasing mitochondrial efficiency with increased proton leak within the first day of life. Our data indicates that one path that leads to PCOS begins at birth and is programmed in utero by androgens.
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作者：
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通讯作者：
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DOI：
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