YAP1 and WWTR1 are required for murine pregnancy initiation.

IF 3.7 3区 生物学 Q1 DEVELOPMENTAL BIOLOGY Reproduction Pub Date : 2024-11-01 DOI:10.1530/REP-24-0355
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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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.

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小鼠妊娠启动需要 YAP1 和 WWTR1。
怀孕成功需要子宫内膜基质细胞蜕膜化。虽然这一过程与生育密不可分,但导致蜕膜化的许多复杂分子机制仍未确定。在人类体外研究中,与子宫内膜基质细胞蜕膜化有关的一个途径是 Hippo 信号途径。之前进行的两项研究表明,Hippo 信号通路的效应因子 YAP1 和 WWTR1 是体外原代子宫内膜基质细胞蜕膜化的必要条件。为了研究 YAP1 和 WWTR1 在体内蜕膜化和妊娠启动中的作用,我们产生了黄体酮受体 Cre 介导的 Yap1 和 Wwtr1 等位基因组合突变。雌性 Yap1 和 Wwtr1 三等位基因突变体在同房后 7.5 天表现出不孕、蜕膜化反应受损、子宫内膜接受能力下降、胚胎发育延迟以及独特的转录特征。大量 mRNA 测序显示,突变体母体在同房后 7.5 天的细胞外基质编码基因发生了显著变化,与子痫前期和子宫内膜异位症等影响生育能力的疾病相关的基因富集,从而证明母体重塑异常。此外,差异表达基因与微阵列确定的雌激素受体和表皮生长因子受体调控基因有方向性重叠。我们的研究结果表明,Yap1 和 Wwtr1 是哺乳动物成功怀孕的必要条件。
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来源期刊
Reproduction
Reproduction 生物-发育生物学
CiteScore
7.40
自引率
2.60%
发文量
199
审稿时长
4-8 weeks
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.
期刊最新文献
SON controls mouse early embryonic development by regulating RNA splicing and histone methylation. IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Systemic and ovarian impacts of heat stress in the porcine model. Phthalate exposure and reproductive effects in rodents: a model for approaches on the protective role of natural products. YAP1 and WWTR1 are required for murine pregnancy initiation. NSUN2 is critical for mouse oocyte meiosis and early embryonic development.
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