Loss of raptor induces Sertoli cells into an undifferentiated state in mice

Biol Reprod. 2022 May 19:ioac104. doi: 10.1093/biolre/ioac104. Online ahead of print.ABSTRACTIn mammals, testis development is triggered by expression of the sex-determining Y-chromosome gene SRY to commit Sertoli cell (SC) fate at gonadal sex determination in the fetus. Several genes have been identified to be required to promote the testis pathway following SRY activation (i.e. SOX9) in embryo; however, largely remains unknown about the genes and mechanisms involved in stabilizing the testis pathway after birth and throughout adulthood. Herein, we report that postnatal males with SC-specific deletion of Raptor demonstrated absence of SC unique identity and adversely acquired granulosa cell-like characteristics, along with loss of tubular architecture and scattered distribution of SCs and germ cells. Subsequent genome-wide analysis by RNA sequencing revealed a profound decrease in the transcripts of testis genes (i.e. Sox9, Sox8, and Amh) and conversely an increase in ovary genes (i.e. Lhx9, Foxl2, and Fst); these changes were further confirmed by immunofluorescence and quantitative reverse-transcription PCR. Importantly, co-immunofluorescence demonstrated that Raptor deficiency induced SCs dedifferentiation into a progenitor state; the Raptor-mutant gonads showed some ovarian somatic cell features, accompanied by enhanced female steroidogenesis and elevated estrogen levels, yet the ZP3-positive terminally feminized oocytes were not observed. In vitro experiments with primar...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research