Przygrodzka Emilia, Myszczynski Kamil, Klos Jan, Ziecik Adam J
Department of Hormonal Action Mechanisms, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland.
Animals (Basel). 2022 Oct 20;12(20):2855. doi: 10.3390/ani12202855.
The corpus luteum plays a fundamental role in regulating reproduction via progesterone production. Still, there is little data on factors regulating the maintenance of luteal function during early pregnancy in gilts. Previous studies emphasize the role of hypoxia and HIF-1 in the regulation of steroidogenic and angiogenic genes expression and progesterone production by ovarian cells. Using the corpus luteum of cyclic and early pregnant gilts we analyzed: (1) the in vitro effects of reduced oxygen tension on progesterone production and mRNA expression of HIF1A and luteal function regulators, STAR and VEGFA; (2) the ex vivo profiles of mRNA and protein expression of HIF-1α, STAR, VEGFA and transcription factors-cJUN and CREB, regulating STAR expression, in the corpus luteum of cyclic and pregnant gilts. The synthesis of progesterone was gradually inhibited in cyclic or pregnant gilt luteal tissue (on day 13 of cycle or pregnancy) incubated in a decreasing concentration−20%, 10%, and 3% of oxygen (O2). Luteal tissues of pregnant gilts produced trace amounts of progesterone in 10% O2, which was similar to cyclic gilts in 3% O2. HIF1A expression increased after 24 h of incubation in tissues of cyclic gilts in 3% vs. 20% O2 (p < 0.01), whereas levels of STAR and VEGFA increased significantly in cyclic and pregnant gilt tissues incubated in 10% and 3% vs. 20% O2. The ex vivo mRNA expression of HIF1A and VEGFA was elevated (p < 0.001) on day 14 vs. day 12 of pregnancy. The protein expression of HIF-1 and VEGFA increased (p < 0.001), whereas the level of STAR (mRNA and protein) and progesterone dropped (p < 0.001) on day 14 of the estrous cycle vs. a parallel day of pregnancy and/or day 12 of the estrous cycle. The content of phosphorylated cJUN and CREB was elevated (p < 0.01) in the luteal tissue on day 12 or 14 of pregnancy vs. parallel days of the estrous cycle. These increases of phosphorylated cJUN and CREB may be involved in STAR expression in the luteal tissue during early pregnancy in gilts.
黄体通过产生孕酮在调节生殖过程中发挥着重要作用。然而，关于后备母猪妊娠早期调节黄体功能维持的因素的数据却很少。先前的研究强调了缺氧和缺氧诱导因子-1（HIF-1）在调节卵巢细胞类固醇生成和血管生成基因表达以及孕酮产生中的作用。我们使用发情周期和妊娠早期后备母猪的黄体进行了分析：（1）低氧张力对孕酮产生以及HIF1A、黄体功能调节因子类固醇生成急性调节蛋白（STAR）和血管内皮生长因子A（VEGFA）mRNA表达的体外影响；（2）发情周期和妊娠后备母猪黄体中HIF-1α、STAR、VEGFA以及调节STAR表达的转录因子c-JUN和环磷腺苷效应元件结合蛋白（CREB）的mRNA和蛋白表达的离体分析。在发情周期或妊娠的后备母猪黄体组织（发情周期或妊娠第13天）中，当在逐渐降低的氧浓度（20%、10%和3%）下孵育时，孕酮的合成逐渐受到抑制。妊娠后备母猪的黄体组织在10%氧气浓度下产生微量孕酮，这与发情周期后备母猪在3%氧气浓度下的情况相似。在3%氧气浓度下孵育24小时后，发情周期后备母猪组织中的HIF1A表达相对于20%氧气浓度时增加（p<0.01），而在10%和3%氧气浓度下孵育的发情周期和妊娠后备母猪组织中，STAR和VEGFA的水平相对于20%氧气浓度时显著增加。与妊娠第12天相比，妊娠第14天HIF1A和VEGFA的离体mRNA表达升高（p<0.001）。与发情周期的平行天数和/或发情周期第12天相比，发情周期第14天HIF-1和VEGFA的蛋白表达增加（p<0.001），而STAR（mRNA和蛋白）水平以及孕酮水平下降（p<0.001）。与发情周期的平行天数相比，妊娠第12天或第14天黄体组织中磷酸化c-JUN和CREB的含量升高（p<0.01）。这些磷酸化c-JUN和CREB的增加可能参与了后备母猪妊娠早期黄体组织中STAR的表达。
