Department of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, Geneva 1211, Switzerland.
Department of Internal Medicine Specialities, HUG, Rue Gabrielle-Perret-Gentil 4, Geneva, Switzerland.
Placenta. 2017 Sep;57:163-169. doi: 10.1016/j.placenta.2017.07.004. Epub 2017 Jul 11.
The unfolded protein response (UPR) is recognized as a key mechanism to promote protein folding and processing in eukaryotes when endoplasmic reticulum stress (ERS) occurs. Some conditions such as hypoxia or glucose deprivation are factors that may elicit ERS response. Recent literature collectively proposes that ERS response is crucial for mammalian reproduction by allowing decidualization and placentation to occur. However, prolonged ERS and activation of UPR pathways can lead to apoptosis and autophagy, which in turn could pose adverse effects on pregnancy outcomes and placentation. ERS associated pregnancy pathologies include intrauterine growth restriction and early-onset preeclampsia. Given these findings, evidence suggests that overactivation of UPR may lead to harmful reproductive circumstances, whereas physiological regulation of ERS response is essential for mammalian reproduction and placental function. In this review, we discuss the dual role of UPR activation with respect to its contribution to placental development as well as pathologies caused by pathway overactivation. In addition, we suggest potential protein markers associated with the UPR, as circulating C-terminal GRP78 or anti-GRP78 autoantibodies which may prove to be of clinical interest.
未折叠蛋白反应（UPR）被认为是真核生物内质网应激（ERS）时促进蛋白质折叠和加工的关键机制。一些条件，如缺氧或葡萄糖剥夺，是可能引发 ERS 反应的因素。最近的文献共同提出，ERS 反应对于哺乳动物的繁殖至关重要，因为它允许蜕膜化和胎盘形成发生。然而，ERS 的持续时间和 UPR 途径的激活可导致细胞凋亡和自噬，这反过来又可能对妊娠结局和胎盘功能产生不利影响。与 ERS 相关的妊娠病理包括宫内生长受限和早发型子痫前期。鉴于这些发现，有证据表明 UPR 的过度激活可能导致有害的生殖情况，而 ERS 反应的生理调节对于哺乳动物的繁殖和胎盘功能是必不可少的。在这篇综述中，我们讨论了 UPR 激活的双重作用，以及它对胎盘发育的贡献以及途径过度激活引起的病理。此外，我们还提出了与 UPR 相关的潜在蛋白质标志物，如循环 C 端 GRP78 或抗-GRP78 自身抗体，这可能具有临床意义。
