Regulatory mechanism of cholesterol sulfate systhtesis in endometrium during implantation period

我们对胚胎着床对子宫内膜的时空调控进行了研究，结果表明，着床期子宫内膜中的硫酸胆固醇(CS)含量呈一过性升高，仅在着床周观察到CS的升高，CS可抑制滋养细胞对子宫内膜的侵袭。本研究旨在阐明子宫内膜在着床过程中CS合成的调控机制。首先，我们试图鉴定合成CS的胆固醇磺基转移酶，并成功地在兔子宫内膜中克隆了SULT家族成员、底物为胆固醇的SULT2B1b。兔SULT2B1b基因编码的蛋白质分子量为37.5 kDa，氨基酸个数为331，与人SULT2B1b基因有87%的同源性。兔SULT2B1b基因的表达在排卵后4d出现一过性升高，与CS的表达模式相一致。此外，SULT2B1b在兔子宫内膜的原位杂交显示该基因只在着床周表达，而在着床部位不表达；然后我们证实了SULT2B1b在人子宫内膜中的表达，并发现该基因在一个月经周期的着床期表达增加。此外，通过检测激素对人子宫内膜间质细胞培养体系中SULT2B1b表达的影响，发现孕酮和cAMP可刺激SULT2B1b的表达。

We have studied on a tempo-spatial control of embryo implantation to uterine endometrium, demonstrating that the content of cholesterol sulfate (CS) in endometrium increases transiently during implantation period, the increase of CS is observed only in peri-implantation region, and CS inhibits the invasion of trophoblast to endometrium. In this study, we aimed to elucidate the regulatory mechanism of CS synthesis in endometrium during implantation.At first we tried to identify cholesterol sulfotransferase which synthesizes CS and succeeded in cloning SULT2B1b in rabbit endometrium cDNA, which was known to be a member of SULT families, and the substrate of which is cholesterol. The rabbit SULT2B1b gene was demonstrated to code the protein of molecular weight 37.5kDa, number of amino acids 331, and to have 87% homology with a human SULT2B1b gene. The expression of rabbit SULT2B1b gene showed a transient rise four days after the ovulation corresponding to the expression patterns of CS. Furthermore, in situ hybridization of SULT2B1b in rabbit endometrium revealed that the gene expressed only in peri-implantation region but not in implantation site.Then, we confirmed the expression of SULT2B1b in human endometrium and found that the gene expression increased during the implantation period in a menstrual cycle. Furthermore, by the examination of hormonal effects on the expression of SULT2B1b in human endometrial interstitial cell culture system, it was indicated that progesterone and cAMP could stimulate the expression of SULT2B1b.