Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.
Life Science Informatics Research Unit, Department of Molecular Biosciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Sci Rep. 2021 May 10;11(1):9842. doi: 10.1038/s41598-021-89052-3.
The in vitro growth (IVG) of human follicles is a potential fertility option for women for whom cryopreserved ovarian tissues cannot be transplanted due to the risk of cancer cell reintroduction; however, there is currently no established method. Furthermore, optimal IVG conditions may differ between the follicles of adult and pre-pubertal females due to molecular differences suggested by basic research. To systematically identify differences between the secondary follicles of adult and pre-pubertal females, a comparative transcriptomic study using mice was conducted herein. Among differentially expressed genes (DEGs), Figla was up-regulated in mature mice. We successfully down-regulated Figla expression in secondary follicle oocytes by a Figla siRNA microinjection, and the subsequent IVG of follicles showed that the diameter of these follicles was smaller than those of controls in mature mice, whereas no significant difference was observed in premature mice. The canonical pathways of DEGs between control and Figla-reduced secondary follicles suggest that Figla up-regulates VDR/RXR activation and down-regulates stem cell pluripotency as well as estrogen signaling. We demonstrated for the first time that folliculogenesis of the secondary follicles of premature and mature mice may be regulated by different factors, such as Figla with its possible target genes, providing insights into optimal IVG conditions for adult and pre-pubertal females, respectively.
人类卵泡的体外生长 (IVG) 是一种潜在的生育选择,适用于因癌症细胞再引入风险而无法移植冷冻卵巢组织的女性;然而,目前尚无既定的方法。此外,由于基础研究表明的分子差异,成人和青春期前女性卵泡的最佳 IVG 条件可能不同。为了系统地识别成年和青春期前女性次级卵泡之间的差异,本文对小鼠进行了比较转录组学研究。在差异表达基因 (DEG) 中,Figla 在成熟小鼠中上调。我们通过 Figla siRNA 微注射成功下调了次级卵泡卵母细胞中的 Figla 表达,随后的卵泡 IVG 表明,这些卵泡在成熟小鼠中的直径小于对照卵泡,而在早产小鼠中则没有观察到显著差异。DEG 之间的经典途径表明,Figla 上调 VDR/RXR 激活,下调干细胞多能性和雌激素信号。我们首次证明,成熟和未成年小鼠次级卵泡的卵泡发生可能受到不同因素的调节,例如 Figla 及其可能的靶基因,这为成年和未成年女性的最佳 IVG 条件提供了见解。