Esencan Ecem, Cozzolino Mauro, Imamoglu Gizem, Seli Emre
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 05610, USA.
Department of Obstetrics and Gynecology, Rey Juan Carlos University, 28933 Madrid, Spain.
Antioxidants (Basel). 2020 Dec 22;10(1):1. doi: 10.3390/antiox10010001.
Mitochondrial unfolded protein response (UPR) is a highly conserved mechanism, which is activated upon cellular or metabolic stress and aims to help cells maintain homeostasis. CLPP (caseinolytic peptidase P) plays a crucial factor for UPR; it promotes the degradation of unfolded mitochondrial proteins. Global germline deletion of in mice results in female infertility and accelerated follicular depletion. Here, we asked whether CLPP is necessary for granulosa/cumulus cell function. mice were generated and crossbred with mice to generate mice with granulosa/cumulus cell-specific deletion (). Mature (8-week-old) female mice (8-week-old) were compared to same age wild type (WT) mice. We found that mature female mice were fertile and produced a similar number of pups per litter compared to WT. Folliculogenesis was not affected by the loss of CLPP in granulosa/cumulus cells as and WT mice had a similar number of primordial, primary, secondary, early antral, and antral follicles. The number of germinal vesicles (GV) and MII oocytes collected from and WT female mice were also similar. Our findings demonstrate that fertility in female mice is not affected by granulosa/cumulus cell-specific UPR disruption through CLPP deletion.
线粒体未折叠蛋白反应（UPR）是一种高度保守的机制，在细胞或代谢应激时被激活，旨在帮助细胞维持体内平衡。CLPP（酪蛋白水解肽酶P）是UPR的关键因子；它促进未折叠线粒体蛋白的降解。小鼠中的CLPP整体生殖系缺失导致雌性不育和卵泡加速耗竭。在此，我们探究CLPP对于颗粒细胞/卵丘细胞功能是否必要。构建了CLPP条件性敲除小鼠，并与他莫昔芬诱导的Cre小鼠杂交以产生颗粒细胞/卵丘细胞特异性CLPP缺失的小鼠（CLPP cKO）。将成熟的（8周龄）CLPP cKO雌性小鼠与同龄野生型（WT）小鼠进行比较。我们发现成熟的CLPP cKO雌性小鼠具有生育能力，与WT小鼠相比每窝产仔数相似。由于CLPP cKO和WT小鼠的原始卵泡、初级卵泡、次级卵泡、早期有腔卵泡和有腔卵泡数量相似，颗粒细胞/卵丘细胞中CLPP缺失并未影响卵泡发生。从CLPP cKO和WT雌性小鼠收集的生发泡（GV）和MII期卵母细胞数量也相似。我们的研究结果表明，雌性小鼠的生育能力不受通过CLPP缺失导致的颗粒细胞/卵丘细胞特异性UPR破坏的影响。
