【摘要】：胎盤形成過程中,伴隨著母體子宮內(nèi)膜螺旋動脈的重塑。螺旋動脈重塑不完整會導致子宮動脈管徑較小、胎盤植入不足等。臨床研究顯示,低水平雌二醇容易造成著床不夠深,而高雌激素水平生產(chǎn)低體重兒的風險增加,可見雌激素對胎盤植入深度存在精細調(diào)控。子宮內(nèi)膜的狀態(tài)是成功受孕的前提之一。月經(jīng)是女性子宮內(nèi)膜發(fā)生周期性脫落的生理現(xiàn)象,研究報道精神因素、工作壓力等會導致女性月經(jīng)不調(diào),月經(jīng)不調(diào)會影響生育。本研究以兔為模型,探討妊娠早期雌激素對胎盤胎兒發(fā)育及血管重塑等方面的影響；以蛻膜化假孕小鼠為模型探討束縛應激對子宮內(nèi)膜的影響。主要結(jié)果如下：1.血管重塑過程中CD31在血管內(nèi)皮細胞逐漸呈強陽性表達,α-SMA呈弱表達或不表達。CD31和α-SMA的表達動態(tài)揭示它們可能參與了妊娠過程中螺旋動脈的重塑。Real-time PCR結(jié)果顯示妊娠9d組IL-8和MCP-1mRNA水平均高于未妊娠組(P0.01),妊娠13d組IL-8和MCP-1mRNA水平均高于妊娠9d組(P0.01),此結(jié)果說明IL-8和MCP-1可能也參與了妊娠過程中螺旋動脈的重塑。2.通過雌激素干預發(fā)現(xiàn),來曲唑處理組妊娠后期胎兒胎盤濕重增加,雌激素處理組胎兒胎盤濕重減少。相對正常對照組,來曲唑處理組妊娠9d時子宮內(nèi)膜血管周空泡化的蛻膜化細胞較少,說明來曲唑處理后子宮內(nèi)膜的蛻膜化啟動被延遲；雌激素處理組妊娠16d時胎盤結(jié)構(gòu)出現(xiàn)異常,連接區(qū)形成受阻。3.CK7+17免疫組織化學結(jié)果顯示,妊娠16d時,來曲唑處理組只在子宮肌層的部分血管內(nèi)檢測到CK7+17陽性信號,雌激素處理組在子宮肌層未檢測到陽性信號。此結(jié)果說明雌激素干預抑制了滋養(yǎng)層細胞的侵襲。4.妊娠9d和妊娠13d時,來曲唑處理組CD31和α-SMA的信號均比正常對照組強；妊娠16d時,雌激素處理組CD31和α-SMA的信號均比正常對照組強。TUNEL的結(jié)果顯示來曲唑處理組妊娠13d時只檢測到零星的血管內(nèi)皮細胞凋亡；妊娠16d時來曲唑處理組與正常對照組無明顯差異,雌激素處理組多數(shù)血管內(nèi)皮細胞處于凋亡狀態(tài)。以上結(jié)果說明雌激素干預后螺旋動脈的重塑被延遲。妊娠9d時,Real-time PCR結(jié)果顯示來曲唑處理組MCP-1 mRNA水平比正常對照組低,而13d時卻比正常對照組高。5.束縛應激組血清中孕酮含量下降,皮質(zhì)酮含量增加,提示孕酮撤退是束縛應激能夠?qū)е峦懩せ募僭行∈笞訉m內(nèi)膜崩解出血的關(guān)鍵因素,且其與皮質(zhì)酮的升高有關(guān)。6.束縛應激組卵巢中孕酮合成相關(guān)酶Cypllal和Star mRNA水平下調(diào)表達,提示束縛應激導致的孕酮撤退與Cypllal和Star mRNA水平的下調(diào)表達有關(guān)。綜上所述,妊娠早期雌激素干預延緩子宮內(nèi)膜螺旋動脈重塑,抑制滋養(yǎng)層細胞侵襲,胎盤結(jié)構(gòu)出現(xiàn)異常。束縛應激通過影響HPA軸和HPO軸導致假孕小鼠子宮內(nèi)膜崩解。
[Abstract]:The process of placental formation is accompanied by remodeling of the mother's endometrial spiral artery. Incomplete remodeling of spiral artery may result in small diameter of uterine artery and insufficient placenta accreta. Clinical studies show that low level estradiol is easy to cause implantation depth, and high level of estrogen production of low birth weight infant risk increased, we can see that estrogen on the depth of placenta accreta has a fine regulation. The state of the endometrium is one of the prerequisites for successful conception. Menstruation is a physiological phenomenon in which female endometrium periodically falls off. It is reported that mental factors, work pressure and so on will lead to irregular menstruation and irregular menstruation will affect fertility. In this study, the effects of estrogen on placental fetal development and vascular remodeling in early pregnancy were studied in rabbits, and the effects of restraint stress on endometrium in decidualized pseudopregnant mice were studied. The main results are as follows: 1. During vascular remodeling, CD31 was strongly expressed in vascular endothelial cells. The dynamic expression of CD31 and 偽-SMA suggests that 偽-SMA may be involved in the remodeling of spiral artery during pregnancy. Real-time PCR results showed that the levels of IL-8 and MCP-1mRNA in 9 day group were higher than those in non-pregnancy group Pregnancy group (P0.01), The levels of IL-8 and MCP-1mRNA in the 13th day group were higher than those in the 9th day group (P0.01), which suggested that IL-8 and MCP-1 might also be involved in the remodeling of the spiral artery during pregnancy. 2. It was found that the fetal placenta wet weight increased in letrozole group and decreased in estrogen treatment group. Compared with the normal control group, there were fewer decidualized cells in letrozole treated group on the 9th day of pregnancy, indicating that the decidualization of endometrium was delayed after letrozole treatment. On the 16th day of gestation, the placental structure was abnormal and the junction area was blocked in estrogen treatment group. The immunohistochemical results of 3.CK7 17 showed that the positive signal of CK7 17 was detected only in some vessels of uterine myometrium in letrozole treatment group at 16 days of gestation. No positive signals were detected in the myometrium of the estrogen treated group. The results suggested that estrogen inhibited the invasion of trophoblast cells. 4. 4. At day 9 and day 13, the signal of CD31 and 偽-SMA in letrozole treated group was stronger than that in normal control group. On the 16th day of gestation, the signals of CD31 and 偽-SMA in estrogen treated group were stronger than those in normal control group. The results of TUNEL showed that only sporadic apoptosis of vascular endothelial cells was detected in letrozole treated group on the 13th day of gestation. On the 16th day of gestation, there was no significant difference between letrozole group and normal control group, and most vascular endothelial cells in estrogen treated group were apoptotic. These results suggest that the remodeling of spiral artery is delayed after estrogen intervention. On the 9th day of gestation, Real-time PCR results showed that the level of MCP-1 mRNA in letrozole treated group was lower than that in normal control group, but at 13 days it was higher than that in normal control group. Serum progesterone content decreased and corticosterone content increased in restraint stress group, which suggested that progesterone withdrawal was the key factor of endometrium collapse and hemorrhage in decidualized pseudopregnant mice, and it was related to the increase of corticosterone. The expression of progesterone synthase related enzymes Cypllal and Star mRNA was down-regulated in the ovary of restraint stress group, suggesting that the withdrawal of progesterone induced by restraint stress was related to the down-regulation of Cypllal and Star mRNA levels. In conclusion, estrogen intervention in early pregnancy delayed endometrial spiral artery remodeling, inhibited trophoblast invasion and abnormal placental structure. Restraint stress induces endometrial disintegration in pseudopregnant mice by affecting the HPA axis and HPO axis.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R714.2

【相似文獻】

相關(guān)期刊論文 前10條

1 薛克勛,高巖,高進;小鼠子宮頸癌14號移植到近交系小鼠后生長特性和轉(zhuǎn)移規(guī)律研究(簡報)[J];中國醫(yī)學科學院學報;1987年02期

2 張榮宜;陳曉蓉;朱坤;;巨噬細胞移動抑制因子在圍植入期小鼠子宮內(nèi)膜中的表達[J];安徽醫(yī)科大學學報;2008年06期

3 李漪;趙永荃;;原位誘發(fā)小鼠子宮，

本文編號：2333842