Expression of steroidogenic genes in maternal and extraembryonic cells during early pregnancy in mice
Expression of steroidogenic genes in maternal and extraembryonic cells during early pregnancy in mice
复制标题
DOI：
10.1210/en.140.11.5220
复制
发表时间：
1999-11-01
期刊：
影响因子：
4.8
通讯作者：
Orly, J
中科院分区：
文献类型：
--
作者：
Arensburg, J;Payne, AH;Orly, J
啮齿类动物妊娠早期类固醇生成的个体发育和功能作用尚不清楚。在之前的研究中，我们已经表明，编码类固醇激素从头合成所必需的两种关键酶的信使RNA（mRNA）的表达是在着床诱导的子宫壁蜕膜化时启动的，即胆固醇侧链裂解细胞色素P450（P450scc）和新鉴定的小鼠3β-羟基类固醇脱氢酶/VI型异构酶同工型（3βHSD VI）。 3β HSD VI mRNA 和蛋白质的原位杂交和免疫组织化学可视化显示，该酶在性交后 6.5-7.5 天的蜕膜抗体细胞中高表达（p.c.）。此后，蜕膜区中 3β HSD VI 的表达消失，并被胚胎巨型滋养层细胞中 mRNA 和蛋白质的高表达所取代。在第 9.5 天的发育高峰期，小鼠巨型滋养层细胞还表达类固醇生成急性调节 (StAR) 蛋白，这是性腺和肾上腺皮质中类固醇生成所必需的。我们的研究结果还表明，在发育中的胎盘中，P450scc、3β HSD VI 和 StAR 蛋白在第 10.5-14.5 天之间的水平下降，这与之前的报道一致，即小鼠胎盘在妊娠后半期不参与类固醇的从头合成。总的来说，本研究的结果表明，在妊娠早期，母体蜕膜和胚胎腔周围滋养层的局部黄体酮合成对于成功植入和/或维持妊娠非常重要。我们建议局部产生的黄体酮在胎儿母体界面充当免疫抑制剂，防止胎儿同种异体移植物的排斥。
The ontogeny and functional role of steroidogenesis during early gestation in rodents is poorly understood. In previous studies, we have shown that expression of messenger RNAs (mRNAs) encoding two key enzymes indispensable for de novo synthesis of steroid hormones, i.e. cholesterol side chain cleavage cytochrome P450 (P450scc) and a newly identified isoform of murine 3 beta-hydroxysteroid dehydrogenase/isomerase type VI (3 beta HSD VI), is initiated upon decidualization of the uterine wall induced by implantation. In situ hybridization and immunohistochemical visualization of 3 beta HSD VI mRNA and protein shows high expression of this enzyme in the antimesometrial cells of the decidua of days 6.5-7.5 post coitum (p.c.). Thereafter, expression of 3 beta HSD VI in the decidual zones disappears and is replaced by a high expression of mRNA and protein in the embryonal giant trophoblast cells. At the peak of their development on day 9.5 p.c., the mouse giant trophoblast cells also express Steroidogenic Acute Regulatory (StAR) protein, which is required for steroidogenesis in the gonads and adrenal cortex. Our findings also suggest that the declining levels of P450scc, 3 beta HSD VI, and StAR proteins between days 10.5-14.5 p.c, in the developing placenta is consistent with previous reports that the mouse placenta is not involved in de novo synthesis of steroids during the second half of pregnancy. Collectively, the results of the present study suggest that, during early phases of pregnancy, local progesterone synthesis in the maternal decidua and the trophoblast layers surrounding the embryonal cavity is important for successful implantation and/or maintenance of pregnancy. We propose that the local production of progesterone acts as an immunosuppressant at the fetal maternal interface preventing the rejection of the fetal allograft.