Throughout the reproductive life of women, cumulus cells (CC) protect the dormant oocyte from damage, act as sensors of the follicular microenvironment, and act as a gatekeeper for oocyte developmental potential. One such mechanism relies on the hypoxia-tolerance response, which, with age, decreases systematically, including in the ovary. We aimed to evaluate the association between gene expression related to hypoxia and aging in CC and reproductive results in in vitro fertilization cycles. We recruited 94 women undergoing controlled ovarian stimulation. Total RNA was extracted from pooled CCs collected after oocyte pick-up (OPU) and reverse-transcribed to complementary DNA using random hexamers to test 14 genes related to hypoxia response via HIF1α activation, oxidative stress, and angiogenic responses. The expression of CLU, NOS2, and TXNIP had a positive correlation with age (r_s = 0.25, r_s = 0.24, and r_s = 0.35, respectively). Additionally, NOS2 and HMOX1 expression correlated positively with the retrieval of immature oocytes (r_s = 0.22 and r_s = 0.40, respectively). Moreover, VEGFC levels decreased overall with increasing fertilization rate, independently of age (r_s = −0.29). We found that the fertilization potential of a cohort of oocytes is related to the ability of CC to respond to oxidative stress and hypoxia with age, pointing at NOS2, HMOX1, and VEGFC expression as markers for oocyte maturation and fertilization success.

中文翻译：

---

卵丘细胞中NOS2、HMOX1和VEGFC的表达水平是卵母细胞成熟和受精率的标志物

在女性的整个生殖生涯中，卵丘细胞 (CC) 保护休眠卵母细胞免受损伤，充当卵泡微环境的传感器，并充当卵母细胞发育潜力的看门人。其中一种机制依赖于耐缺氧反应，随着年龄的增长，耐缺氧反应会系统性降低，包括在卵巢中。我们的目的是评估 CC 中与缺氧和衰老相关的基因表达与体外受精周期中生殖结果之间的关联。我们招募了 94 名接受受控卵巢刺激的女性。从卵母细胞拾取 (OPU) 后收集的汇集 CC 中提取总 RNA，并使用随机六聚体反转录为互补 DNA，以通过 HIF1α 激活、氧化应激和血管生成反应来测试与缺氧反应相关的 14 个基因。CLU、NOS2、TXNIP的表达与_年龄呈正相关（分别为rs ₌  0.25、rs ₌  0.24、rs  =0.35）。此外，NOS2和HMOX1表达与未成熟卵母细胞的回收呈正相关（_分别为rs  = 0.22 和_rs =  0.40）。此外，随着受精率的增加， VEGFC水平总体下降，与年龄无关 ( r _s  = -0.29)。我们发现，一群卵母细胞的受精潜力与 CC 对氧化应激和缺氧随年龄增长的反应能力有关，指出 NOS2、HMOX1 和 VEGFC 表达是卵母细胞成熟和受精成功的标志。