通过孕激素对人类胚胎囊托菲克托德和细胞内部质量的差异基因调节
Kathryn Shaia Snow1, Douglas J Raburn1, Thomas M Price2
1Division of Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology, Duke University, 5601 Arringdon Park Dr Suite 210, Morrisville, NC, 27560, USA.
Reproductive sciences (Thousand Oaks, Calif.)
|December 27, 2023
概括
人类胚胎细胞利用线粒体的孕激素受体 (PR-M),而不是核受体 (nPR),在托菲克托德和内细胞质中. 孕激素主要促进细胞增殖在托菲克托皮.
科学领域:
- 生殖生物学 生殖生物学
- 发育生物学是发展生物学.
- 分子内分泌学分子内分泌学
背景情况:
- 孕激素 (P4) 在人类植入前胚胎发育中的作用尚未完全理解.
- 关于孕激素对人类胚胎细胞的具体作用的现有知识缺口.
- 需要阐明早期人类胚胎发生过程中孕信号传递的机制.
研究的目的:
- 为了确定线粒体孕激素受体 (PR-M) 在人体胚胎囊中皮 (TE) 和内细胞质 (ICM) 的表达.
- 为了研究从裂变到母细胞阶段的发育过程中TE和ICM中孕激素诱导的基因表达变化.
- 为了比较核孕激素受体 (nPR) 和人体胚胎囊中的PR-M的表达.
主要方法:
- 用孕激素 (10−6M) 或载体对冷保存的人类分裂期胚胎的处理.
- 从euploid母细胞囊中剖析TE和ICM以进行RNA测序 (RNA-seq).
- 在剖析细胞和人类胚胎干细胞系 (HESCs) 中分析PR-M和nPR表达.
主要成果:
- 线粒体孕激素受体 (PR-M) 表达在TE,ICM和HESC中得到证实;核孕激素受体 (nPR) 表达在TE和ICM中不存在.
- 孕激素在TE (183个途径) 中显著影响基因表达,超过ICM (27个途径).
- TE显示了对DNA复制和细胞增殖的上调基因 (例如,F-Box关联域含有),而ICM通路主要是下调的 (例如,染色体分离).
结论:
- 人类胚胎细胞在TE和ICM中表达PR-M,但不表达nPR.
- 孕激素在TE和ICM之间差异调节基因表达.
- 孕激素主要刺激人体芽细胞的TE细胞的细胞增殖.
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