School of Biological Sciences, University of Sydney, Sydney, Australia.
J Exp Zool B Mol Dev Evol. 2012 Mar;318(2):148-58. doi: 10.1002/jez.b.22003.
Structural and functional changes to the uterus associated with maintenance of pregnancy are controlled primarily by steroid hormones such as progesterone. We tested the hypothesis that progesterone regulates uterine structural changes during pregnancy in the viviparous skink, Pseudemoia entrecasteauxii, by treating pregnant females with the progesterone receptor antagonist mifepristone at different stages of pregnancy. Expression and distribution of progesterone receptor was determined using Western blot and immunohistochemistry. During early pregnancy, mifepristone treatment resulted in altered uterine epithelial cell surface morphology and high embryo mortality, but did not affect females at mid and late stages of pregnancy. Females treated with mifepristone in early pregnancy exhibited abnormal uterine epithelial cell morphology such as lateral blebbing and presence of wide gaps between cells indicating loss of intercellular attachment. Chorioallantoic membranes of the embryo were not affected by mifepristone treatment. Two isoforms (55 kDa and 100 kDa) of progesterone receptor were identified using immunoblots and both isoforms were localized to the nucleus of uterine epithelial cells. The 55 kDa isoform was expressed throughout pregnancy, whereas the 100 kDa isoform was expressed during mid and especially late pregnancy. In P. entrecasteauxii, mifepristone may prevent successful embryo attachment in early pregnancy through its effects on uterine epithelial cells but may have little effect on pregnancy once the maternal-embryo structural relationship is established.
与妊娠维持相关的子宫结构和功能变化主要受甾体激素如孕酮控制。我们通过在妊娠的不同阶段用孕酮受体拮抗剂米非司酮处理怀孕的雌性蜥蜴 Pseudemoia entrecasteauxii 来测试孕酮在胎生蜥蜴妊娠期间调节子宫结构变化的假说。使用 Western blot 和免疫组织化学测定孕酮受体的表达和分布。在妊娠早期,米非司酮处理导致子宫上皮细胞表面形态改变和高胚胎死亡率,但对妊娠中期和晚期的雌性没有影响。在妊娠早期用米非司酮处理的雌性表现出异常的子宫上皮细胞形态,如侧向泡状和细胞间存在宽间隙,表明细胞间附着丧失。胚胎的绒毛尿囊膜不受米非司酮处理的影响。使用免疫印迹鉴定了两种孕酮受体同工型(55 kDa 和 100 kDa),两种同工型均定位于子宫上皮细胞的核内。55 kDa 同工型在整个妊娠期间表达,而 100 kDa 同工型在妊娠中期和特别是妊娠晚期表达。在 P. entrecasteauxii 中,米非司酮可能通过对子宫上皮细胞的作用来防止妊娠早期胚胎的成功附着,但一旦建立了母体-胚胎的结构关系,它对妊娠的影响可能很小。