Yoo Inkyu, Jung Wonchul, Lee Soohyung, Cheon Yugyeong, Ka Hakhyun
Department of Biological Science and Technology, Yonsei University, Wonju 26493, Korea.
Anim Biosci. 2022 Apr;35(4):533-543. doi: 10.5713/ab.21.0307. Epub 2021 Sep 15.
Caspase-mediated apoptosis plays a crucial role in the regulation of endometrial and placental function in females. Caspase activity is tightly controlled by members of the inhibitors of apoptosis proteins (IAPs) family. However, the expression and regulation of IAPs at the maternal-conceptus interface has not been studied in pigs. Therefore, we determined the expression of IAP family members baculovirus IAP repeat-containing 1 (BIRC1) to BIRC6 at the maternal-conceptus interface in pigs.
We obtained endometrial tissues from pigs at various stages of the estrous cycle and pregnancy, conceptus tissues during early pregnancy, and chorioallantoic tissues during mid- to late pregnancy and analyzed the expression of IAPs. Furthermore, we determined the effects of the steroid hormones estradiol-17β (E2) and progesterone on the expression of IAPs in endometrial explant tissue cultures.
During the estrous cycle, BIRC2 and BIRC5 expression varied cyclically, and during pregnancy, endometrial BIRC1, BIRC2, BIRC3, BIRC4, and BIRC5 expression varied in a stage-specific manner. Conceptus and chorioallantoic tissues also expressed IAPs during pregnancy. The BIRC2 and BIR3 mRNAs were localized to luminal epithelial cells, and BIRC4 proteins to glandular epithelial cells in the endometrium. Exposure of endometrial tissues to E2 increased the expression of BIRC6, while progesterone increased the expression of BIRC1, BIRC4, and BIRC6 in a dose-dependent manner.
These results indicated that IAPs were expressed in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in a stage-specific manner. In addition, steroid hormones were found to be responsible for the expression of some IAPs in pigs. Together, the results suggested that IAPs may play important roles in endometrial and placental functions by regulating caspase action and apoptosis at the maternal-conceptus interface.
半胱天冬酶介导的细胞凋亡在雌性动物子宫内膜和胎盘功能的调节中起着关键作用。半胱天冬酶活性受凋亡抑制蛋白（IAPs）家族成员的严格控制。然而，猪母胎界面处IAPs的表达和调控尚未得到研究。因此，我们测定了猪母胎界面处IAP家族成员杆状病毒IAP重复序列包含蛋白1（BIRC1）至BIRC6的表达。
我们获取了处于发情周期和妊娠期不同阶段的猪子宫内膜组织、妊娠早期的胎体组织以及妊娠中后期的绒毛尿囊组织，并分析了IAPs的表达。此外，我们还测定了甾体激素雌二醇-17β（E2）和孕酮对子宫内膜外植体组织培养中IAPs表达的影响。
在发情周期中，BIRC2和BIRC5的表达呈周期性变化，在妊娠期，子宫内膜中BIRC1、BIRC2、BIRC3、BIRC4和BIRC5的表达呈现阶段特异性变化。胎体和绒毛尿囊组织在妊娠期也表达IAPs。BIRC2和BIR3 mRNA定位于子宫内膜的腔上皮细胞，BIRC4蛋白定位于腺上皮细胞。子宫内膜组织暴露于E2会增加BIRC6的表达，而孕酮则以剂量依赖的方式增加BIRC1、BIRC4和BIRC6的表达。
这些结果表明，IAPs在发情周期的子宫内膜以及妊娠期的母胎界面以阶段特异性方式表达。此外，发现甾体激素负责猪体内某些IAPs的表达。总之，这些结果表明IAPs可能通过调节母胎界面处的半胱天冬酶作用和细胞凋亡在子宫内膜和胎盘功能中发挥重要作用。
