Liver receptor homolog-1 is essential for pregnancy.
Liver receptor homolog-1 is essential for pregnancy.
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肝受体同源物 1 对于怀孕至关重要
作者：
成功怀孕需要多个组织的一系列信号和因素的协调。其中一个元素，肝受体同源物-1 (Lrh-1)，是一个孤儿核受体，调节代谢和激素合成。它在鼠类和人的卵巢卵泡颗粒细胞和黄体中强烈表达。nr5a2（也称为Lrh-1）是编码Lrh-1的基因，在小鼠的种系消融在原肠胚形成时具有胚胎致命性。卵巢卵泡中Lrh-1的缺失表明，它调节类固醇合成和排卵所需的基因。为了研究Lrh-1对小鼠妊娠的影响，我们通过基因破坏其在黄体中的表达，导致黄体功能不全。激素替代允许胚胎植入，但随后出现妊娠失败，伴有子宫内膜脱胎化受损、胎盘形成受损、胎儿生长迟缓和胎儿死亡。Lrh-1也在小鼠和人子宫内膜中表达，在人子宫内膜基质细胞的原代培养中，通过RNA干扰降低nr5a2转录物丰度可消除去个位化。这些发现表明Lrh-1对于维持黄体、促进脱个体化和胎盘的形成是必要的。因此，它在建立和维持妊娠方面具有多种不可或缺的作用。
Successful pregnancy requires coordination of an array of signals and factors from multiple tissues. One such element, liver receptor homolog-1 (Lrh-1), is an orphan nuclear receptor that regulates metabolism and hormone synthesis. It is strongly expressed in granulosa cells of ovarian follicles and in the corpus luteum of rodents and humans. Germline ablation ofNr5a2(also calledLrh-1), the gene coding for Lrh-1, in mice is embryonically lethal at gastrulation. Depletion of Lrh-1 in the ovarian follicle shows that it regulates genes required for both steroid synthesis and ovulation. To study the effects of Lrh-1 on mouse gestation, we genetically disrupted its expression in the corpus luteum, resulting in luteal insufficiency. Hormone replacement permitted embryo implantation but was followed by gestational failure with impaired endometrial decidualization, compromised placental formation, fetal growth retardation and fetal death. Lrh-1 is also expressed in the mouse and human endometrium, and in a primary culture of human endometrial stromal cells, reduction ofNR5A2transcript abundance by RNA interference abrogated decidualization. These findings show that Lrh-1 is necessary for maintenance of the corpus luteum, for promotion of decidualization and for formation of the placenta. It therefore has multiple, indispensible roles in establishing and sustaining pregnancy.
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