Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam‑do 627‑706, Republic of Korea.
Department of Pediatrics, Biomedical Research Institute, Pusan National University School of Medicine, Busan 302‑739, Republic of Korea.
Int J Mol Med. 2018 May;41(5):2943-2951. doi: 10.3892/ijmm.2018.3474. Epub 2018 Feb 8.
Estrogen and progesterone are the main pregnancy hormones produced by the placenta. It is well understood that estrogen stimulates angiogenesis in the uterus during the reproductive cycle. Although the estrogen and progesterone signaling pathways are assumed to be associated with placental vascularization and preeclampsia, expression of estrogen receptors (ESRs) and progesterone receptor (PGR) in the placenta have not been well studied. The present study examined the expression patterns of steroid hormone receptors in placentas. Human placenta samples were collected and divided into normal and preeclampsia groups. Results revealed that expression levels of ESR1 were reduced, whereas ESR2 and PGR were elevated in preeclamptic placentas. To generate an in vitro preeclampsia environment, human placenta‑derived BeWo cells were incubated under hypoxic conditions, or treated with catechol‑O‑methyl transferase inhibitor (COMT‑in) or L‑NG‑nitroarginine methyl ester (L‑NAME). Expression levels of ESR1, ESR2 and PGR in hypoxic cells demonstrated similar regulation as those in placentas from women with preeclampsia. Although COMT‑in and L‑NAME did not significantly regulate the expression levels of the receptors, COMT‑in translocated ESR2 and PGR from the nucleus to the cytoplasm, indicating that these receptors were inactivated. These results suggested that ESRs and PGR are associated with symptoms of preeclampsia in the placenta. The expression of ESR1 was reduced in preeclamptic placenta and hypoxic BeWo cells. In addition, the activation of ESR2 and PGR was blocked in placenta cells subjected to COMT‑in treatment. The reduced ESR1 expression and inactivation of ESR2 and PGR proteins may affect the physiological complications of preeclampsia in the placenta.
雌激素和孕激素是胎盘产生的主要妊娠激素。人们已经充分了解到，雌激素在生殖周期中会刺激子宫中的血管生成。虽然雌激素和孕激素信号通路被认为与胎盘血管化和子痫前期有关，但胎盘中雌激素受体（ESR）和孕激素受体（PGR）的表达尚未得到很好的研究。本研究检查了甾体激素受体在胎盘中的表达模式。收集人胎盘样本并分为正常和子痫前期组。结果表明，子痫前期胎盘中 ESR1 的表达水平降低，而 ESR2 和 PGR 的表达水平升高。为了产生体外子痫前期环境，将人胎盘衍生的 BeWo 细胞在低氧条件下孵育，或用儿茶酚-O-甲基转移酶抑制剂（COMT-in）或 L- NG-硝基精氨酸甲酯（L-NAME）处理。缺氧细胞中 ESR1、ESR2 和 PGR 的表达水平与子痫前期妇女胎盘中的调节相似。虽然 COMT-in 和 L-NAME 并未显著调节受体的表达水平，但 COMT-in 将 ESR2 和 PGR 从核内转移到细胞质中，表明这些受体失活。这些结果表明，ESR 和 PGR 与胎盘子痫前期的症状有关。在子痫前期胎盘和低氧 BeWo 细胞中，ESR1 的表达减少。此外，在 COMT-in 处理的胎盘细胞中，ESR2 和 PGR 的激活被阻断。ESR1 表达减少和 ESR2 和 PGR 蛋白失活可能会影响胎盘子痫前期的生理并发症。
