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 Figlaexpression 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.
Fig: Differentially expressed genes in secondary follicle oocytes between mature and premature mice. (a) Representative pictures of the secondary follicles of (i) a mature mouse and (ii) premature mouse. Scale bars, 50 µm. (b) Heatmap of differentially expressed genes (DEGs, log2 fold change > 0.5, false discovery rate (FDR) < 0.01). Four samples from mature and premature mice were compared. (c) Expression levels of Figla in the secondary follicle oocytes of mature mice and premature mice by qRT-PCR (n = 6, in each group).
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.
Okunomiya, A., Horie, A., Tani, H. et al. Figla promotes secondary follicle growth in mature mice. Sci Rep 11, 9842 (2021). https://doi.org/10.1038/s41598-021-89052-3