Primordial follicle activation is affected by the absence of Sohlh1 in mice

Abstract

Previous studies have reported that only primordial follicles and empty follicles can be found in 7.5 days postparturition (dpp) Sohlh1−/− mouse ovaries and females are infertility. There appears to be a defect in follicle development during the primordial‐to‐primary follicle transition in Sohlh1−/− mouse ovaries. However, detailed analyses of these phenomena have not been performed. In this study, we used Sohlh1−/− transgenic mice to explore the role of Sohlh1 in folliculogenesis. The results showed that only primordial follicles and empty follicles can be observed in Sohlh1−/− ovaries from 0.5 to 23.5 dpp. The expression of Foxo3 and FOXO3 was downregulated; nucleocytoplasmic shuttling of FOXO3 was normal in 7.5‐dpp Sohlh1+/+ but not Sohlh1−/− ovaries; and primordial follicle activation (PFA) was not observed in 7.5‐dpp Sohlh1−/− mice. The expression levels of KIT, AKT, and P308‐AKT were downregulated (p < 0.05), whereas that of P473‐AKT was not significantly changed (p > 0.05). The KIT/PI3K/AKT pathway was inhibited. Furthermore, we conducted a dual luciferase assay and chromatin immunoprecipitation. The results showed that SOHLH1 can upregulate the Kit gene by binding to the −3698 bp E‐box motif. The absence of Sohlh1 may affect PFA in mouse ovaries via downregulation of Kit and inhibition of the KIT/PI3K/AKT pathway.

The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles in vivo

“…Sohlh1 is specifically expressed in germ cell cysts and oocytes of primordial follicles in female mice, and Sohlh1-null mice are sterile due to a defect of follicle development during the primordial-to-primary follicle transition (Pangas et al, 2006). In Sohlh1 −/− mice, only primordial follicles and empty follicles can be observed in ovaries from 0.5 to 23.5 days post-parturition, and primordial follicle activation was not observed at 7.5 days post-parturition (Liu et al, 2019). The possible mechanism is that the absence of Sohlh1 may affect the activation of primordial follicles via the downregulation of KIT and the inhibition of the KIT/PI3K/Akt pathway (Liu et al, 2019).…”

“…In Sohlh1 –/– mice, only primordial follicles and empty follicles can be observed in ovaries from 0.5 to 23.5 days post-parturition, and primordial follicle activation was not observed at 7.5 days post-parturition ( Liu et al, 2019 ). The possible mechanism is that the absence of Sohlh1 may affect the activation of primordial follicles via the downregulation of KIT and the inhibition of the KIT/PI3K/Akt pathway ( Liu et al, 2019 ). Compared with its expression in mice, Sohlh1 exhibits a much more extensive expression pattern in human tissues and is mainly located in the oocytes of primordial and primary follicles, granular cells, and theca cells of secondary follicles ( Zhang et al, 2015 ).…”