Genna E Moldovan, Noura Massri, Erin L Vegter, Ivonne N Pauneto-Delgado, Gregory W Burns, Niraj Joshi, Bin Gu, Ripla Arora, Asgerally T Fazleabas
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引用次数: 0
Abstract
Endometrial stromal cell decidualization is required for pregnancy success. Although this process is integral to fertility, many of the intricate molecular mechanisms contributing to decidualization remain undefined. One pathway that has been implicated in endometrial stromal cell decidualization in humans in vitro, is the Hippo signaling pathway. Two previously conducted studies showed that the effectors of the Hippo signaling pathway, YAP1 and WWTR1, are required for decidualization of primary endometrial stromal cells in vitro. To investigate the in vivo role of YAP1 and WWTR1 in decidualization and pregnancy initiation, we generated Progesterone receptor Cre mediated mutation of a combination of Yap1 and Wwtr1 alleles. Female Yap1 and Wwtr1 triple allele mutants exhibited subfertility, a compromised decidualization response, decreased endometrial receptivity, delayed embryonic development, and a unique transcriptional profile at 7.5 days post coitus. Bulk mRNA sequencing revealed aberrant maternal remodeling evidenced by significant alterations in extracellular matrix encoding genes at 7.5 days post-coitus in mutant dams and enrichment for terms associated with fertility-compromising diseases like pre-eclampsia and endometriosis. In addition, differentially expressed genes overlapped directionally with Estrogen receptor and Epidermal growth factor receptor regulated genes as identified by microarray. Our results indicate that Yap1 and Wwtr1 are necessary for successful mammalian pregnancy initiation.
期刊介绍:
Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction.
Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease.
Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.