Acquisition of endometrial receptivity for embryo implantation is one of the crucial processes during pregnancy and is induced mainly by progesterone and enhanced by conceptus signals. Prokineticin 1 (PROK1) is characterized as a secretory protein with diverse functions in various tissues, including the reproductive tract. PROK1, with its receptor PROKR1, are up-regulated in the porcine endometrium during implantation and in women’s receptive endometrium and decidua. However, the function of PROK1 in embryo-maternal communication has still not been fully elucidated. Hence, we hypothesize that PROK1 is involved in endometrial receptivity development and implantation in pigs. In this study, using the porcine in vivo model of intrauterine infusions of estradiol-17β (E2) and prostaglandin E2 (PGE2), we revealed that these hormones elevated endometrial expression of PROK1 and PROKR1 mRNA, respectively. Moreover, E2, acting synergistically with PGE2, increased PROKR1 protein expression. We also evidenced that PROK1–PROKR1 signaling induced expression of following genes and/or proteins CCN2, CDH13, FGF2, NFATC2, ANGPT1, ANGPT2, CDH1, MUC4, SPP1, IFNG, IL6, LIF, LIFR, TNF, TGFB3, and FGF9, as well as phosphorylation of PTK2 and secretion of IL6 and IL11 by endometrial explants in vitro. Ingenuity pathway analysis revealed that functions associated with the PROK1-regulated genes/proteins include cell-to-cell contact, cell attachment, migration and viability, differentiation of epithelial tissue, leukocyte migration, inflammatory response, angiogenesis, and vasculogenesis. Summarizing, our study suggests that PROK1 acts pleiotropically as an embryonic signal mediator that regulates endometrial receptivity by increasing the expression of the genes and proteins involved in implantation and pregnancy establishment in pigs.

中文翻译：

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在妊娠建立和胚胎植入过程中，前动力蛋白 1 在猪子宫内膜中的多效性作用†

获得胚胎植入的子宫内膜容受性是怀孕期间的关键过程之一，主要由黄体酮诱导，受孕信号增强。Prokineticin 1 (PROK1) 的特点是在包括生殖道在内的各种组织中具有多种功能的分泌蛋白。PROK1及其受体PROKR1在植入期间在猪子宫内膜以及在女性的接受子宫内膜和蜕膜中上调。然而，PROK1 在胚胎-母体交流中的功能仍未完全阐明。因此，我们假设 PROK1 参与了猪的子宫内膜容受性发育和植入。在这项研究中，使用 estradiol-17β (E2) 和前列腺素 E2 (PGE2) 宫内输注的猪体内模型，PROK1和PROKR1mRNA，分别。此外，E2 与 PGE2 协同作用，增加了 PROKR1 蛋白的表达。我们还证明了 PROK1-PROKR1 信号传导诱导以下基因和/或蛋白质 CCN2、CDH13、FGF2、NFATC2、ANGPT1、ANGPT2、CDH1、MUC4、SPP1、IFNG、IL6、LIF、LIFR、TNF、TGFB3 和 FGF9 的表达，以及体外子宫内膜外植体对 PTK2 的磷酸化和 IL6 和 IL11 的分泌。Ingenuity 通路分析表明，与 PROK1 调节的基因/蛋白质相关的功能包括细胞间接触、细胞附着、迁移和活力、上皮组织的分化、白细胞迁移、炎症反应、血管生成和血管生成。总结，