Jang Hwanhee, Choi Yohan, Yoo Inkyu, Han Jisoo, Hong Jin Su, Kim Yoo Yong, Ka Hakhyun
Department of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
PLoS One. 2017 Oct 31;12(10):e0187221. doi: 10.1371/journal.pone.0187221. eCollection 2017.
Vitamin D is a secosteroid hormone with many varied functions including regulation of blood calcium levels, cell proliferation, immunity, and reproduction in mammals. Vitamin D is activated by 25-hydroxylase (CYP2R1) and 1-alpha-hydroxylase (CYP27B1) and is degraded by 24-hydroxylase (CYP24A1). Vitamin D is transported by vitamin D-binding protein (group-specific component, GC) through the bloodstream and regulates cellular actions by binding to vitamin D receptor (VDR). In this study, we determined the expression and regulation of vitamin D-related molecules and the role of vitamin D at the maternal-conceptus interface in pigs. Vitamin D-metabolizing enzymes CYP2R1, CYP27B1, and CYP24A1, vitamin D binding protein GC, and vitamin D receptor VDR were expressed in the endometrium in a pregnancy stage-specific manner as well as in conceptus and chorioallantoic tissues during pregnancy. VDR protein was localized to endometrial and trophoblastic cells. Concentrations of calcitriol, the active form of vitamin D, in the endometrial tissues were higher during early pregnancy than in mid- to late pregnancy, while plasma concentrations of calcitriol were highest during late pregnancy. Furthermore, calcitriol affected the expression of several genes related to conceptus implantation, vitamin D metabolism, calcium ion regulation, PG metabolism, and calcium-binding proteins in endometrial tissue explants. These results show that CYP2R1, CYP27B1, CYP24A1, GC, and VDR were expressed at the maternal-conceptus interface, endometrial calcitriol levels were regulated during pregnancy, and calcitriol modulated the expression of endometrial genes, suggesting that calcitriol may play an important role in the establishment and maintenance of pregnancy by regulating endometrial function in pigs.
维生素D是一种甾体激素，具有多种功能，包括调节哺乳动物的血钙水平、细胞增殖、免疫和生殖。维生素D由25-羟化酶（CYP2R1）和1-α-羟化酶（CYP27B1）激活，并由24-羟化酶（CYP24A1）降解。维生素D通过维生素D结合蛋白（组特异性成分，GC）在血液中运输，并通过与维生素D受体（VDR）结合来调节细胞活动。在本研究中，我们确定了猪母体-胎儿界面处维生素D相关分子的表达和调控以及维生素D的作用。维生素D代谢酶CYP2R1、CYP27B1和CYP24A1、维生素D结合蛋白GC以及维生素D受体VDR在子宫内膜中以妊娠阶段特异性方式表达，在妊娠期间的胎儿和绒毛膜尿囊组织中也有表达。VDR蛋白定位于子宫内膜和滋养层细胞。子宫内膜组织中维生素D的活性形式骨化三醇的浓度在妊娠早期高于妊娠中期和晚期，而血浆骨化三醇浓度在妊娠晚期最高。此外，骨化三醇影响子宫内膜组织外植体中与胚胎着床、维生素D代谢、钙离子调节、PG代谢以及钙结合蛋白相关的几个基因的表达。这些结果表明，CYP2R1、CYP27B1、CYP24A1、GC和VDR在母体-胎儿界面处表达，妊娠期间子宫内膜骨化三醇水平受到调控，且骨化三醇调节子宫内膜基因的表达，提示骨化三醇可能通过调节猪的子宫内膜功能在妊娠的建立和维持中发挥重要作用。
