Hayashi K, Burghardt R C, Bazer F W, Spencer T E
Center for Animal Biotechnology and Genomics, 442 Kleberg Center, 2471 TAMU, Texas A & M University, College Station, Texas 77843-2471, USA.
Endocrinology. 2007 Jul;148(7):3496-506. doi: 10.1210/en.2007-0283. Epub 2007 Apr 12.
WNTs (Wingless-type MMTV integration site family member) are involved in critical developmental and growth processes in animals. These studies investigated WNT pathways in the ovine uterus and conceptus during the periimplantation period of pregnancy. WNT2 and WNT2B mRNAs were detected in endometrial stroma. WNT5A and WNT5B mRNAs were most abundant in the stroma and less so in the luminal epithelium, whereas WNT11 mRNA was detected primarily in the glands. WNT7A mRNA was present in the luminal epithelium on d 10, absent on d 12 and 14, and increased between d 16 and 20. Only WNT2, WNT2B, and WNT4 were detected in conceptus trophectoderm. FZD6/8 (frizzled receptor) and GSK3B (glycogen synthase kinase 3beta) mRNAs were detected primarily in endometrial epithelia and conceptus trophectoderm, whereas the LRP5/6 (low-density lipoprotein receptor-related proteins 5 and 6) coreceptor was present in all endometrial cells and the trophectoderm. DKK1 (Dickkopf), a WNT signaling inhibitor, increased in the endometrium from d 16-20. CTNNB1 [catenin (cadherin associated protein) beta1] and CDH1 (E-cadherin) mRNAs were most abundant in the endometrial epithelia and trophectoderm. LEF1 (lymphoid enhancer-binding factor 1) mRNA was expressed primarily in uterine epithelia, whereas TCF7L2 [(transcription factor 7-like 2 (T-cell specific, HMG-box)] was primarily in the conceptus. CTNNB1 and TCF7L2 proteins were both abundant in the nuclei of trophoblast giant binucleate cells. WNT7A stimulated a TCF/LEF-luciferase reporter activity in ovine trophectoderm cells that was inhibited by dominant-negative TCF and Sfrp2 (secreted FZD-related protein 2). WNT7A increased trophectoderm cell proliferation as well as MSX2 (msh homeobox 2) and MYC (myelocytomatosis oncogene) mRNA levels. Wnt5a increased trophectoderm cell migration in a Rho kinase-dependent manner. These results support the hypotheses that canonical and noncanonical WNT signaling pathways are conserved regulators of conceptus-endometrial interactions in mammals and regulate periimplantation ovine conceptus development.
WNTs（无翅型MMTV整合位点家族成员）参与动物关键的发育和生长过程。这些研究调查了妊娠植入前期绵羊子宫和孕体中的WNT信号通路。在子宫内膜基质中检测到WNT2和WNT2B mRNA。WNT5A和WNT5B mRNA在基质中最为丰富，在腔上皮中较少，而WNT11 mRNA主要在腺体中检测到。WNT7A mRNA在第10天存在于腔上皮中，在第12天和14天不存在，在第16天至20天之间增加。在孕体滋养外胚层中仅检测到WNT2、WNT2B和WNT4。FZD6/8（卷曲受体）和GSK3B（糖原合酶激酶3β）mRNA主要在子宫内膜上皮和孕体滋养外胚层中检测到，而LRP5/6（低密度脂蛋白受体相关蛋白5和6）共受体存在于所有子宫内膜细胞和滋养外胚层中。WNT信号抑制剂DKK1在第16天至20天期间在子宫内膜中增加。CTNNB1 [连环蛋白（钙黏着蛋白相关蛋白）β1]和CDH1（E-钙黏着蛋白）mRNA在子宫内膜上皮和滋养外胚层中最为丰富。LEF1（淋巴细胞增强因子结合因子1）mRNA主要在子宫上皮中表达，而TCF7L2 [转录因子7样2（T细胞特异性，HMG盒）]主要在孕体中表达。CTNNB1和TCF7L2蛋白在滋养层巨双核细胞的细胞核中均很丰富。WNT7A刺激绵羊滋养外胚层细胞中的TCF/LEF荧光素酶报告活性，该活性被显性负性TCF和Sfrp2（分泌型FZD相关蛋白2）抑制。WNT7A增加滋养外胚层细胞增殖以及MSX2（msh同源盒2）和MYC（髓细胞瘤癌基因）mRNA水平。Wnt5a以Rho激酶依赖性方式增加滋养外胚层细胞迁移。这些结果支持以下假设：经典和非经典WNT信号通路是哺乳动物中孕体-子宫内膜相互作用的保守调节因子，并调节植入前期绵羊孕体的发育。
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