Analyses of the influence of maternal stress on the implantation of mouse embryo

背景：卵巢内分泌因素对胚胎着床的成功起着重要作用。但也有部分患者卵巢功能正常，足以诱导子宫内膜分化，为妊娠、去个体化做好准备，但仍未能怀孕。尽管最近有了抗逆转录病毒技术的发展，这种植入失败的病人很难治疗。众所周知，慢性应激可引起各种生殖障碍，包括排卵和流产。然而，母体应激对胚胎着床的影响尚不清楚。因此，我们分析母体应激是否影响小鼠胚胎着床。结果：我们首先考察了应激对正常妊娠、假妊娠和胚胎移植小鼠生殖功能的影响。两组均有产妇应激导致妊娠流产。然而，这些发现是压力引起的卵巢功能障碍的结果，而不是植入失败本身。我们接下来研究了应力对延迟着床模型的影响。该模型在卵巢切除后外源性替代卵巢功能，因此可以在不影响卵巢功能的情况下研究应激对胚胎着床的影响。然而，卵巢切除术的手术压力似乎掩盖了随后的慢性压力的影响。因此，我们制备了切除卵巢的雌性小鼠，并在补充外源性卵巢类固醇后移植小鼠囊胚。通过雌二醇预处理以及在植入期给药雌二醇/孕酮，与常规假妊娠和胚胎移植模型相比，我们成功地诱导了令人满意的着床率。与对照组相比，胚胎移植前3d持续超声应激显著抑制着床率。目前，我们正在利用cDNA微阵列分析研究这种应激诱导小鼠着床失败的基因谱。结论：应激本身可导致小鼠着床失败。进一步的研究可能会阐明这种应激诱导的着床失败的机制，从而导致不明原因着床失败的新治疗策略的发展。少

Background : It has been proposed that ovarian endocrine factors play an important role for the successful implantation. However, some patients fail to pregnant even though their ovarian function appears normal and enough to induce endometrial differentiation to prepare pregnancy, decidualization. Such patients, implantation failure, are difficult to treat in spite of the recent development of ART. It is well known that chronic stress induces various reproductive disorder including aovulation and abortion. However, the influence of maternal stress on embryo implantation is not well clarified. Therefore, we analyzed whether maternal stress affect the mouse embryo implantation.Results : At first, we examined the influence of stress on the reproductive function of normal pregnant or pseudopregnant and embryo-transferred mouse. Maternal stress induced pregnancy loss in both groups. However, these findings were the results of stress induced ovarian dysfunction rather than the implantation f … More ailure itself. We nextly examined the influence of stress on delayed implantation model. This model replaces ovarian function exogenously after ovariectomy, so it appeared possible to investigate the influence of stress on embryo implantation without affecting ovarian function. However, surgical stress of ovariectomy appeared to obscure the influence of subsequent chronic stress.Therefore, we prepared ovariectomized female mice and transferred murine blastocysts after supplementation of exogenous ovarian steroids. By the pretreatment with estradiol in addition to estradiol/ progesterone administration during peri-implantation period, we succeeded to induce satisfactory implantation rate compared with conventional pseudopregnant and embryo transfer model Using this mouse model, we examined the influence of maternal stress on the implantation of mouse embryo. Continuous ultrasonic stress from 3days before the embryo transfer significantly suppressed implantation rate compared with control group. Presently, we are investigating the gene profile of this stress induced mouse implantation failure using cDNA microarray analysis.Conclution : We could demonstrated that stress itself induces implantation failure in mouse. Further investigation might clarify the mechanism of this stress induced implantation failure, which would lead to the development of a novel treatment strategy of unexplained implantation failure. Less