A uterine decidual cell cytokine ensures pregnancy-dependent adaptations to a physiological stressor
A uterine decidual cell cytokine ensures pregnancy-dependent adaptations to a physiological stressor
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DOI：
10.1242/dev.02743
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发表时间：
2007-01-15
期刊：
影响因子：
4.6
通讯作者：
Soares, Michael J.
中科院分区：
文献类型：
--
作者：
Alam, S. M. Khorshed;Konno, Toshihiro;Soares, Michael J.
在小鼠中，蜕膜细胞从子宫基质细胞分化，以响应类固醇激素和胚胎产生的信号。蜕膜细胞在创造有利于胚胎发育的子宫内环境中起着至关重要的作用。在它们的许多功能中，是产生与催乳素（PRL）相关的细胞因子，包括蜕膜催乳素相关蛋白（DPRP）。DPRP是一种肝素结合细胞因子，在子宫蜕膜中大量表达。本研究分离了小鼠Dprp基因，对其结构进行了表征，并对其生物学功能进行了评价。通过用框内增强型绿色荧光蛋白（EGFP）基因和新霉素（neo）抗性盒替换Dprp基因的外显子2至6来制备Dprp缺失小鼠。突变小鼠的杂合杂交育种产生了预期的孟德尔比率。怀孕的杂合子女性表达EGFP的蜕膜组织内的位置相同的内源性Dprp mRNA和蛋白质表达。纯合子Dprp无效突变雄性和雌性小鼠存活，表现出正常的出生后生长速率，具有生育能力，并产生正常的窝仔数。一个突出的表型时，观察到怀孕的Dprp基因敲除小鼠暴露于生理应激。DPRP缺乏干扰妊娠依赖性缺氧适应，导致妊娠失败。妊娠终止与子宫系膜蜕膜细胞畸变、系膜血管完整性和绒毛尿囊胎盘形态发生中断有关。观察表明，DPRP参与妊娠依赖的适应生理应激。
In the mouse, decidual cells differentiate from uterine stromal cells in response to steroid hormones and signals arising from the embryo. Decidual cells are crucially involved in creating the intrauterine environment conducive to embryonic development. Among their many functions is the production of cytokines related to prolactin ( PRL), including decidual prolactin-related protein (DPRP). DPRP is a heparin-binding cytokine, which is abundantly expressed in uterine decidua. In this investigation, we have isolated the mouse Dprp gene, characterized its structure and evaluated its biological role. Dprp-null mice were made by replacing exons 2 to 6 of the Dprp gene with an in-frame enhanced green fluorescent protein (EGFP) gene and a neomycin (neo) resistance cassette. Heterozygous intercross breeding of the mutant mice yielded the expected mendelian ratio. Pregnant heterozygote females expressed EGFP within decidual tissue in locations identical to endogenous Dprp mRNA and protein expression. Homozygous Dprp-null mutant male and female mice were viable, exhibited normal postnatal growth rates, were fertile and produced normal litter sizes. A prominent phenotype was observed when pregnant Dprp-null mice were exposed to a physiological stressor. DPRP deficiency interfered with pregnancy-dependent adaptations to hypoxia resulting in pregnancy failure. Termination of pregnancy was associated with aberrations in mesometrial decidual cells, mesometrial vascular integrity, and disruptions in chorioallantoic placenta morphogenesis. The observations suggest that DPRP participates in pregnancy-dependent adaptations to a physiological stressor.