Department of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.
Graduate Institute of Veterinary Medicine, National Taiwan University, 10617, Taipei, Taiwan.
J Ovarian Res. 2024 Mar 19;17(1):66. doi: 10.1186/s13048-024-01388-2.
Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function.
We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions.
Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.
休止谷胱甘肽硫转移酶 2（QSOX2）是一种黄素腺嘌呤二核苷酸依赖性巯基氧化酶，已知其通过氧化活性参与蛋白质折叠、细胞生长调节和氧化还原状态修饰。早期的研究表明 QSOX2 在雄性生殖道中的组织和细胞定位，以及 QSOX2 蛋白合成和表达的高度调节机制是通过睾酮和附睾丰富的氨基酸谷氨酸的协调作用实现的。然而，QSOX2 在女性生殖中的存在和功能尚不清楚。在这项研究中，我们应用 Cre-loxP 基因操作系统生成杂合和纯合 Qsox2 敲除小鼠，并检查其对卵巢功能的影响。
我们证明 QSOX2 存在于卵巢卵泡的所有阶段的卵泡支持细胞（颗粒细胞和卵丘细胞）中，但不存在于黄体中，表明其在卵泡发生中起支持作用。与野生型小鼠的生殖器官发生相比，雄性 Qsox2 敲除小鼠的睾丸和附睾结构没有差异；然而，Qsox2 敲除破坏了雌性小鼠的正常排卵过程，因为黄体形成明显减少，并且当雄性与纯合 Qsox2 敲除雌性交配时，没有怀孕。RNAseq 分析进一步表明，Qsox2 敲除改变了负责维持卵巢功能的关键信号通路和基因。
我们的数据首次表明 Qsox2 对小鼠的卵巢功能至关重要。
