A uterine decidual cell cytokine ensures pregnancy-dependent adaptations to a physiological stressor

Abstract

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 Dprpnull 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.

Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure

“…Notably, increased Igfbp1 expression in vivo does not necessarily infer a heightened decidual reaction but may reflect a compensatory maternal response to a suboptimal or failing pregnancy 35 . In agreement, expression of Prl8a2, a mouse decidual marker gene related to human PRL 10 , was significantly lower in Sgk1 -/-animals ( Supplementary Fig. 13).…”

“…This 'window of implantation', confined to 2 to 4 days during the mid-secretory phase of the cycle, enables the embryo to contact and stably adhere to the endometrial luminal epithelium before invading the decidualizing stroma [7][8][9] . Decidualization, which denotes the transformation of stromal fibroblasts into specialized secretory decidual cells, is indispensable for pregnancy as it governs local immune responses, controls trophoblast invasion, and protects the conceptus against a variety of physiological stressors associated with pregnancy [10][11][12] . Failure of the endometrium to express a receptive phenotype is a major cause of conception delay and IVF treatment failure.…”

Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites

“…To characterize this uterine failure and to establish precisely the time of embryonic death, WT and Cbs-KO female mice were mated with their corresponding male mice. Females were killed on postcoital days 4,8,12, and 16, representing important steps of the gestation process such as preimplantation, placentation, organogenesis, fetal growth, and development. Furthermore, to investigate potential mechanisms involved in the uterine failure at the transcriptional level, we carried out high-throughput microarray analyses at a time-period close to embryonic death, studied gene expression 1 Plasma analyses.…”

Significance of glutathione peroxidases in endometrium function: facts, hypotheses, and research perspectives

“…В связи с этим перспективным подходом для проверки этой ги-потезы являются оценка размера приплода у жи-вотных, содержащихся на селенодефицитной диете в периимплантационный период и под-вергающихся воздействию стрессовых факторов, и оценка гомоцистеинпероксидазной активно-сти в эндометрии в тех же условиях и в тот же период. Как известно, помещение генетически нормальных мышей в условия гипобарической гипоксии (концентрация кислорода -11 %) с 5,5-го по 11,5-й день беременности приводит к гибели части эмбрионов [26]. Перспективной представляется попытка предотвращения гибе-ли имплантировавшихся эмбрионов в данных условиях за счет применения препаратов селена.…”

“…GPX3, возможно, является белком, присут-ствие которого в эндометрии необходимо для сохранения беременности в условиях гипоксии, в стрессовых условиях. На возможность этого также указывает известный факт зависимости экспрессии Gpx3 от гипоксия-индуцибельного фактора HIF1α [23,26].…”