Satterfield M Carey, Song Gwonhwa, Hayashi Kanako, Bazer Fuller W, Spencer Thomas E
Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
Reprod Fertil Dev. 2008;20(8):935-46. doi: 10.1071/rd08069.
WNT signalling regulates cell proliferation, differentiation, polarity and organisation. The present study investigated the effects of progesterone (P4) on the endometrial WNT system in relation to blastocyst development and growth in sheep. Ewes received daily intramuscular injections of either corn oil (CO) vehicle or 25 mg P4 from 36 h after mating (Day 0) until hysterectomy on Day 9 or 12. Another group received P4 until Day 8 and 75 mg mifepristone (RU486) from Day 8 to Day 12. Early P4 treatment increased blastocyst growth on Days 9 and 12, whereas no blastocysts were recovered from P4 + RU486-treated ewes. Levels of WNT2 mRNA in the stroma and WNT11 and WNT7A mRNAs in the endometrial luminal epithelia (LE) were reduced in P4 + RU486-treated ewes on Day 9, whereas WNT11 mRNA was reduced in the endometria of both P4- and P4 + RU486-treated ewes on Day 12. On Day 12, WNT2 mRNA was increased in the stroma, WNT7A mRNA was increased in the LE and WNT5A mRNA was increased in the LE and stroma of P4 + RU486- compared with P4-treated ewes. DKK1 mRNA was absent in the endometrial stroma of P4 + RU486-treated ewes. Expression of transcription factor 7 like-2 (TCF7L2) was transiently increased in endometrial epithelia of P4-treated ewes on Day 9, but decreased in these ewes on Day 12. MSX1 mRNA was decreased by P4 treatment on Day 9 and levels of both MSX1 and MSX2 mRNA were higher in P4 + RU486-treated ewes on Day 12. Thus, P4 modulates the endometrial WNT system and elicits a transient decline in selected WNT pathways and signalling components, which is hypothesised to alter tight and adherens junctions, thereby stimulating blastocyst growth and development.
WNT信号通路调控细胞增殖、分化、极性和组织形成。本研究调查了孕酮（P4）对绵羊子宫内膜WNT系统的影响，以及与囊胚发育和生长的关系。母羊在配种后36小时（第0天）开始每天肌肉注射玉米油（CO）载体或25毫克P4，直至第9天或第12天进行子宫切除。另一组母羊在第8天前接受P4注射，从第8天到第12天接受75毫克米非司酮（RU486）注射。早期P4处理在第9天和第12天增加了囊胚的生长，而在接受P4 + RU486处理的母羊中未回收囊胚。在第9天，接受P4 + RU486处理的母羊基质中WNT2 mRNA水平以及子宫内膜腔上皮（LE）中WNT11和WNT7A mRNA水平降低，而在第12天，接受P4和P4 + RU486处理的母羊子宫内膜中WNT11 mRNA均降低。在第12天，与接受P4处理的母羊相比，接受P4 + RU486处理的母羊基质中WNT2 mRNA增加，LE中WNT7A mRNA增加，LE和基质中WNT5A mRNA增加。在接受P4 + RU486处理的母羊子宫内膜基质中未检测到DKK1 mRNA。转录因子7样2（TCF7L2）的表达在第P4处理的母羊子宫内膜上皮中在第9天短暂增加，但在这些母羊第12天时降低。MSX mRNA在第9天因P4处理而降低，在第12天接受P4 + RU486处理的母羊中MSX1和MSX2 mRNA水平均较高。因此，P4调节子宫内膜WNT系统，并引发特定WNT途径和信号成分的短暂下降，据推测这会改变紧密连接和黏附连接，从而刺激囊胚的生长和发育。
