Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation.
Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation.
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DOI：
10.1371/journal.pone.0010258
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发表时间：
2010-04-21
期刊：
影响因子：
3.7
通讯作者：
Macklon NS
中科院分区：
文献类型：
--
作者：
Teklenburg G;Salker M;Molokhia M;Lavery S;Trew G;Aojanepong T;Mardon HJ;Lokugamage AU;Rai R;Landles C;Roelen BA;Quenby S;Kuijk EW;Kavelaars A;Heijnen CJ;Regan L;Brosens JJ;Macklon NS
妊娠被广泛认为是依赖于一个亲密的对话，介导的局部分泌因子之间的发育能力的胚胎和接受子宫内膜。然而，人类的生殖成功是有限的，主要是因为染色体异常植入前胚胎的高患病率。此外，人类子宫内膜容受性的短暂时期与子宫内膜基质细胞（ESCs）分化为高度特化的蜕膜细胞（在没有妊娠的情况下总是触发月经）相一致。子宫内膜周期性蜕膜化在着床过程中的作用以及介导与胚胎串扰的蜕膜细胞因子和生长因子的性质尚不清楚。我们采用了人类共培养模型，包括蜕膜化胚胎干细胞和单孵化囊胚，以确定参与着床的可溶性因子。在3天的共培养期间，大约75%的胚胎停滞，而其余的胚胎显示正常发育。用多重免疫分析法测定基质细胞分泌的14种着床因子的水平。令人惊讶的是，发育中的胚胎的存在对蜕膜分泌物没有显著影响，除了IL-5水平的适度降低。相比之下，停止胚胎引发强烈的反应，其特征在于选择性抑制IL-1β、IL-6、IL-10、IL-17、IL-18、嗜酸性粒细胞趋化因子和HB-EGF分泌。用未分化的ESC重复共培养，但没有一种分泌的细胞因子受到发育或停滞胚胎的影响。人胚胎干细胞在分化为蜕膜细胞后成为胚胎质量的生物传感器。鉴于人类植入前胚胎中总染色体错误的发生率很高，周期性蜕膜化随后月经脱落可能代表了一种自然胚胎选择机制，限制了母体对发育受损妊娠的投资。
Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown. We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1β, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo. Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies.
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DOI：
10.1073/pnas.0806219105
发表时间：
2008-10-21
影响因子：
11.1
作者：
Grewal, Seema;Carver, Janet G.;Mardon, Helen J.
通讯作者：
Mardon, Helen J.
影响因子：
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Boomsma, C. M.;Kavelaars, A.;Macklon, N. S.
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DOI：
10.1073/pnas.0802355105
发表时间：
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DOI：
10.1073/pnas.0812722106
发表时间：
2009-04-07
影响因子：
11.1
作者：
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通讯作者：
Renard, Jean-Paul
影响因子：
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作者：
Haig, D
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Haig, D