Laboratorio de Medicina Reproductiva, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531. S2002LRK, Rosario, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.
Cell Tissue Res. 2024 Sep;397(3):275-285. doi: 10.1007/s00441-024-03911-9. Epub 2024 Aug 6.
The complex interactome crucial for successful pregnancy is constituted by the intricate network of endocrine and paracrine signaling pathways, involving gametes, embryos, and the female reproductive tract. Specifically, the oviduct exhibits distinct responses to gametes and early embryos during particular phases of the estrus cycle, a process tightly regulated by reproductive hormones. Moreover, these hormones play a pivotal role in orchestrating cyclical changes within oviductal epithelial cells. To unravel the molecular mechanisms underlying these dynamic changes, our study aimed to investigate the involvement of protein kinase A (PKA) in oviductal epithelial cells throughout the estrus cycle and in advanced pregnancy, extending our studies to oviductal epithelial cell in primary culture. By a combination of 2D-gel electrophoresis, Western blotting, and mass spectrometry, we identified 17 proteins exhibiting differential phosphorylation status mediated by PKA. Among these proteins, we successfully validated the phosphorylation status of heat shock 70 kDa protein (HSP70), aconitase 2 (ACO2), and lamin B1 (LMNB1). Our findings unequivocally demonstrate the dynamic regulation of PKA throughout the estrus cycle in oviductal epithelial cells. Also, analysis by bioinformatics tools suggest its pivotal role in mediating cyclical changes possibly through modulation of apoptotic pathways. This research sheds light on the intricate molecular mechanisms underlying reproductive processes, with implications for understanding fertility and reproductive health.
成功妊娠所必需的复杂相互作用组由内分泌和旁分泌信号通路的复杂网络构成,涉及配子、胚胎和女性生殖道。具体而言,输卵管在发情周期的特定阶段对配子和早期胚胎表现出明显的反应,这一过程受生殖激素的严格调节。此外,这些激素在协调输卵管上皮细胞的周期性变化中起着关键作用。为了揭示这些动态变化背后的分子机制,我们的研究旨在调查蛋白激酶 A(PKA)在发情周期和晚期妊娠期间在输卵管上皮细胞中的参与情况,并将我们的研究扩展到原代培养的输卵管上皮细胞。通过 2D-凝胶电泳、Western 印迹和质谱分析的组合,我们鉴定出 17 种蛋白,这些蛋白的磷酸化状态受 PKA 介导。在这些蛋白中,我们成功验证了热休克 70kDa 蛋白(HSP70)、 aconitase 2(ACO2)和 lamin B1(LMNB1)的磷酸化状态。我们的研究结果明确表明 PKA 在发情周期中在输卵管上皮细胞中进行动态调节。此外,生物信息学工具的分析表明,它通过调节凋亡途径在介导周期性变化中起着关键作用。这项研究揭示了生殖过程背后复杂的分子机制,对理解生育能力和生殖健康具有重要意义。