Scholtz Kathrine E, Penny Clem B, Hosie Margot J
School of Anatomical Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
Cell Biol Int. 2008 Apr;32(4):436-46. doi: 10.1016/j.cellbi.2007.12.015. Epub 2008 Jan 11.
During the window of receptivity, a narrow range of time under the control of the ovarian hormones progesterone and oestrogen, when a blastocyst can attach to the uterine surface, the plasma membrane of the uterine epithelial cells undergoes a remarkable change in structure, known as 'the plasma membrane transformation' of early pregnancy. RU486, the controversial abortion drug (Mifegyne), acts as a progesterone receptor antagonist, resulting in transcriptionally inactive progesterone receptors. In view of this, a change in the well-documented sequences of the plasma membrane transformation is postulated. This study therefore aims to investigate the effects of RU486 on this sequence of events in the implantation and non-implantation sites of the rat uterus. In both RU486 treated and control animals, on days 4.5, 5.5 and 6.5 of pregnancy, scanning electron microscopy revealed a distinct pattern of folding of the uterine surface in non-implantation sites. In contrast, folding was not observed within the implantation sites. These results indicate that surface alterations are probably not under the control of progesterone signalling. The lack of folding at the implantation sites possibly ensures maximum close contact between the blastocyst and the maternal tissue thus promoting implantation. During early pregnancy, specifically on day 5.5, the microvilli of the uterine epithelial cells in the treated animals were more dense than those in the untreated animals. Such microvilli are characteristic of the uterine epithelial cells of a uterus under-stimulated by hormones. Flattening of the apical cell borders usually seen at the time of blastocyst attachment and implantation was not observed following RU486 treatment. Large apical protrusions were observed in the RU486 treated animals only, possibly linked in some way to apoptosis. The antiprogestin properties of RU486 may further elucidate the progesterone effects associated with early pregnancy.
在接受期,即在卵巢激素孕酮和雌激素控制下的一段狭窄时间内,当囊胚能够附着于子宫表面时,子宫上皮细胞的质膜会发生显著的结构变化,即早孕时的“质膜转变”。RU486,即有争议的堕胎药(米非司酮),作为一种孕酮受体拮抗剂,会导致转录失活的孕酮受体。鉴于此,推测质膜转变的已有记录序列会发生变化。因此,本研究旨在探究RU486对大鼠子宫着床部位和未着床部位这一系列事件的影响。在RU486处理组和对照组动物中,在妊娠第4.5、5.5和6.5天,扫描电子显微镜显示未着床部位子宫表面有明显的折叠模式。相比之下,着床部位未观察到折叠。这些结果表明,表面改变可能不受孕酮信号的控制。着床部位缺乏折叠可能确保了囊胚与母体组织之间的最大紧密接触,从而促进着床。在妊娠早期,特别是在第5.5天,处理组动物子宫上皮细胞的微绒毛比未处理组动物的更密集。这种微绒毛是激素刺激不足的子宫的子宫上皮细胞的特征。RU486处理后未观察到在囊胚附着和着床时通常可见的顶端细胞边界变平。仅在RU486处理的动物中观察到大的顶端突起,可能以某种方式与细胞凋亡有关。RU486的抗孕酮特性可能会进一步阐明与早孕相关的孕酮作用。