Cadenas Jesús, Adrados Cristina Subiran, Kristensen Stine Gry, Macklon Kirsten Tryde, Greve Vinnie Hornshøj, Fedder Jens, Mamsen Linn Salto, Andersen Claus Yding
Laboratory of Reproductive Biology, The Juliane Marie Center for Women, Children, and Reproduction, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
The Fertility Clinic, University Hospital of Copenhagen, Copenhagen, Denmark.
Mol Reprod Dev. 2025 Jun;92(6):e70035. doi: 10.1002/mrd.70035.
This study assessed transcriptional changes in human cumulus cells (CCs) during oocyte maturation In Vitro. CCs were collected from 25 cumulus-oocyte complexes derived from surplus ovarian medulla tissue of eight women (mean age 29 years, range 19-36) undergoing ovarian tissue cryopreservation without ovarian stimulation. Samples included CCs from fresh germinal vesicle (GV) oocytes (n = 5), and from GV (n = 8) and metaphase II (MII) oocytes (n = 12) after 48 h of In Vitro maturation (IVM). Microarray analysis revealed active signaling pathways during IVM, emphasizing LHCGR upregulation as central to oocyte maturation. Enhanced pathways included the insulin-like growth factor (IGF) system, particularly IGF2, and activin/inhibin signaling, while others appeared less active In Vitro compared to In Vivo. Differential expression analysis identified 1763 significantly expressed genes (DEGs) between fresh GV and MII-IVM, 50 DEGs between GV-IVM and MII-IVM, and 339 novel or unknown transcripts. Clustering highlighted additional pathways, such as MAPK, PPAR, Wnt, cholesterol metabolism, PI3K-AKT, TGF-β, focal adhesion, actin cytoskeleton regulation, and RANK/RANKL, with differential regulation during IVM. These findings underscore the complexity of signaling in CCs and the distinct regulatory mechanisms of human oocyte maturation In Vitro compared to In Vivo.
本研究评估了卵母细胞体外成熟过程中人类卵丘细胞（CCs）的转录变化。CCs取自25个卵丘-卵母细胞复合体，这些复合体来自8名接受卵巢组织冷冻保存且未进行卵巢刺激的女性（平均年龄29岁，范围19 - 36岁）的多余卵巢髓质组织。样本包括来自新鲜生发泡（GV）期卵母细胞的CCs（n = 5），以及体外成熟（IVM）48小时后来自GV期（n = 8）和中期II（MII）期卵母细胞的CCs（n = 12）。微阵列分析揭示了IVM过程中的活跃信号通路，强调促黄体生成素/绒毛膜促性腺激素受体（LHCGR）上调是卵母细胞成熟的核心。增强的通路包括胰岛素样生长因子（IGF）系统，特别是IGF2，以及激活素/抑制素信号传导，而与体内相比，其他通路在体外似乎活性较低。差异表达分析确定了新鲜GV期和MII-IVM期之间有1763个显著表达基因（DEGs），GV-IVM期和MII-IVM期之间有50个DEGs，以及339个新的或未知的转录本。聚类突出了其他通路，如丝裂原活化蛋白激酶（MAPK）、过氧化物酶体增殖物激活受体（PPAR）、Wnt、胆固醇代谢、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K-AKT）、转化生长因子-β（TGF-β）、粘着斑、肌动蛋白细胞骨架调节以及核因子κB受体活化因子/核因子κB受体活化因子配体（RANK/RANKL），它们在IVM过程中存在差异调节。这些发现强调了CCs中信号传导的复杂性以及与体内相比人类卵母细胞体外成熟的独特调节机制。
