Pregnancy establishment in mammals, including pigs, requires proper communication between embryos and the maternal reproductive tract. Prokineticin 1 (PROK1) has been described as a secretory protein with pleiotropic functions and as a novel tissue-specific angiogenic factor. However, despite the studies performed mainly on human cell lines and in mice, the function of PROK1 in the endometrium during early pregnancy is still not fully elucidated. We hypothesized that PROK1 contributes to pregnancy establishment in the pig. The present study is the first to report that the expression of PROK1 and its receptor (PROKR1) is elevated in the porcine endometrium during implantation and the early placentation period. PROK1 protein was detected mainly in luminal epithelial cells, glandular epithelial cells and blood vessels in the endometrium. Using the porcine in vivo model of unilateral pregnancy, we revealed that conceptuses induced the endometrial expression of PROK1 and PROKR1. Moreover, the embryonic signal, estradiol-17β, as well as progesterone, stimulated the endometrial expression of PROK1 and PROKR1. We also evidenced that PROK1-PROKR1 signaling supports endometrial angiogenesis in the pig. The PROK1-stimulated proliferation of primary porcine endometrial endothelial (PEE) cells involved PI3K/AKT/mTOR, MAPK, cAMP and NFKB signaling pathways. Furthermore, PROK1 via PROKR1 promoted the formation of capillary-like structures by PEE cells. PROK1 also stimulated VEGFA and PGF2α secretion, which in turn, may indirectly support angiogenic changes within endometrial tissue. In summary, our study suggests that PROK1 acts as an embryonic signal mediator that regulates endometrial angiogenesis and secretory function during implantation and early placentation in pigs.

中文翻译：

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Prokineticin 1-prokineticin 受体 1 信号促进妊娠期间猪子宫内膜的血管生成†。

哺乳动物（包括猪）的妊娠建立需要胚胎和母体生殖道之间的适当沟通。Prokineticin 1 (PROK1) 已被描述为一种具有多效功能的分泌蛋白和一种新型的组织特异性血管生成因子。然而，尽管研究主要在人类细胞系和小鼠身上进行，但 PROK1 在妊娠早期子宫内膜中的功能仍未完全阐明。我们假设 PROK1 有助于猪的妊娠建立。本研究首次报道了在着床和胎盘早期的猪子宫内膜中PROK1及其受体（PROKR1）的表达升高。PROK1蛋白主要在子宫内膜的管腔上皮细胞、腺上皮细胞和血管中检测到。使用猪单侧妊娠的体内模型，我们发现conceptuses 诱导子宫内膜表达PROK1 和PROKR1。此外，胚胎信号雌二醇-17β 以及孕酮刺激了 PROK1 和 PROKR1 的子宫内膜表达。我们还证明 PROK1-PROKR1 信号支持猪的子宫内膜血管生成。PROK1 刺激的原代猪子宫内膜内皮 (PEE) 细胞增殖涉及 PI3K/AKT/mTOR、MAPK、cAMP 和 NFKB 信号通路。此外，PROK1 通过 PROKR1 促进 PEE 细胞形成毛细血管样结构。PROK1 还刺激了 VEGFA 和 PGF2α 的分泌，这反过来可能间接支持子宫内膜组织内的血管生成变化。总之，