The roles of AKT isoforms in decidualization and embryo implantation using a PGR-Cre mouse model.

IF 3.1 2区 生物学 Q2 REPRODUCTIVE BIOLOGY
Pascal Adam, François Fabi, Sophie Parent, Léa-Isabelle Renaud, Monique Cadrin, Eric Asselin
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引用次数: 0

Abstract

Implantation is a complex process requiring a prepared, receptive endometrium, reliant on synchronized decidualization of stromal cells. During this process, cell proliferation and apoptosis are tightly regulated by signaling factors, including the survival and proliferation PI3K/AKT pathway. The three AKT isoforms each play distinct physiological roles but their specific functions in endometrial cell survival and apoptosis remain unclear. We hypothesize that for successful implantation, each AKT isoform has distinct roles in the endometrium during decidualization, which varies throughout the process. To explore this, we developed a unique PGR-Cre tissue-specific mouse model with single and combined knockouts (KO) of each AKT isoform. Using artificial decidualization during pseudopregnancy and normal gestation, we investigated the specific activity of each AKT isoform and their downstream targets to assess the role of AKT pathway. Our results showed that the AKT1-2 KO genotype failed to decidualize during pseudopregnancy and exhibited a reduced number of implantation sites. Interestingly, AKT3 was hyperphosphorylated in the AKT1-2 KO mice and emerged as the primary isoform active throughout decidualization, specifically signaling through GSK3B. This study suggests distinct yet partially redundant roles for AKT1 and AKT2 during decidualization and embryo implantation. We propose that the AKT pathway plays significant role in fertility, and a deeper understanding of its involvement in decidualization could lead to improved strategies for addressing fertility issues. These findings highlight the importance of AKT activity in the cellular and molecular regulation of mouse fertility.

AKT同种异构体在PGR-Cre小鼠模型的去个体化和胚胎着床中的作用。
植入是一个复杂的过程,需要一个准备好的、可接受的子宫内膜,依赖于基质细胞的同步脱胞。在这一过程中,细胞增殖和凋亡受到包括PI3K/AKT通路在内的信号因子的严格调控。这三种AKT亚型各有不同的生理作用,但在子宫内膜细胞存活和凋亡中的具体功能尚不清楚。我们假设,对于成功植入,每个AKT亚型在子宫内膜去个体化过程中都有不同的作用,在整个过程中都是不同的。为了探索这一点,我们开发了一种独特的PGR-Cre组织特异性小鼠模型,该模型具有每个AKT亚型的单敲除和联合敲除(KO)。通过假妊娠和正常妊娠期间的人工去个体化,我们研究了每种AKT亚型及其下游靶点的特异性活性,以评估AKT通路的作用。我们的研究结果表明,AKT1-2 KO基因型在假妊娠期间未能脱个体化,并且表现出着床部位数量减少。有趣的是,AKT3在AKT1-2 KO小鼠中被过度磷酸化,并成为在脱个体化过程中活跃的主要亚型,特别是通过GSK3B发出信号。这项研究表明,AKT1和AKT2在脱个体化和胚胎着床过程中发挥着不同但部分重复的作用。我们提出AKT通路在生育中发挥重要作用,对其参与去个性化的深入了解可能会导致解决生育问题的改进策略。这些发现强调了AKT活性在小鼠生育能力的细胞和分子调控中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology of Reproduction
Biology of Reproduction 生物-生殖生物学
CiteScore
6.30
自引率
5.60%
发文量
214
审稿时长
1 months
期刊介绍: Biology of Reproduction (BOR) is the official journal of the Society for the Study of Reproduction and publishes original research on a broad range of topics in the field of reproductive biology, as well as reviews on topics of current importance or controversy. BOR is consistently one of the most highly cited journals publishing original research in the field of reproductive biology.
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