National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 4, Oparina st., Moscow, 117997, Russia.
Molecular Medicine Institute, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation, 8, Trubetskaya st., Moscow, 119991, Russia.
Sci Rep. 2019 Apr 2;9(1):5501. doi: 10.1038/s41598-019-41996-3.
Calcium plays a role of universal cellular regulator in the living cell and one of the crucial regulators of proper fetal development during gestation. Mitochondria are important for intracellular calcium handling and signaling. Mitochondrial calcium uniporter (mtCU) is a multiprotein complex of the mitochondrial inner membrane responsible for the transport of calcium to the mitochondrial matrix. In the present study, we analyzed the expression level of mtCU components in two parts of the feto-maternal system - placenta and myometrium at full-term delivery and at preterm birth (PTB) on different stages: 22-27, 28-32, 33-36 weeks of gestation (n = 50). A gradual increase of mRNA expression and changes in protein content of MCU and MICU1 subunits were revealed in the placenta during gestation. We also observed slower depolarization rate of isolated placental mitochondria induced by Ca2+ titration at PTB. In myometrium at PTB relative gene expression level of MCU, MCUb and SMDT1 increased as compared to full-term pregnancy, but the tendency to gradual increase of MCU protein simultaneous with MCUb increase and MICU1 decline was shown in gestational dynamics. Changes observed in the present study might be considered both natural dynamics as well as possible pathological mechanisms underlying preterm birth.
钙在活细胞中起着普遍的细胞调节剂的作用，是妊娠期间胎儿正常发育的关键调节剂之一。线粒体对于细胞内钙处理和信号转导很重要。线粒体钙单向转运蛋白（mtCU）是一种位于线粒体内膜的多蛋白复合物，负责将钙转运到线粒体基质中。在本研究中，我们分析了胎-母系统的两个部分（胎盘和子宫）中 mtCU 成分的表达水平，在足月分娩和早产（PTB）时的不同阶段：22-27、28-32、33-36 周妊娠（n=50）。在妊娠期间，胎盘的 mcu 和 mICU1 亚基的 mRNA 表达水平逐渐增加，蛋白含量也发生变化。我们还观察到，在 PTB 时，通过钙离子滴定诱导的分离胎盘线粒体去极化率较慢。在 PTB 的子宫中，与足月妊娠相比，MCU、MCUb 和 SMDT1 的相对基因表达水平增加，但随着 MCUb 增加和 MICU1 下降，MCU 蛋白逐渐增加的趋势表明了妊娠期间的动力学变化。本研究中观察到的变化既可以被认为是自然动态，也可以被认为是早产的潜在病理机制。
