Gonadal Sex Differentiation and Ovarian Organogenesis along the Cortical–Medullary Axis in Mammals

Abstract

In most mammals, the sex of the gonads is based on the fate of the supporting cell lineages, which arises from the proliferation of coelomic epithelium (CE) that surfaces on the bipotential genital ridge in both XY and XX embryos. Recent genetic studies and single-cell transcriptome analyses in mice have revealed the cellular and molecular events in the two-wave proliferation of the CE that produce the supporting cells. This proliferation contributes to the formation of the primary sex cords in the medullary region of both the testis and the ovary at the early phase of gonadal sex differentiation, as well as to that of the secondary sex cords in the cortical region of the ovary at the perinatal stage. To support gametogenesis, the testis forms seminiferous tubules in the medullary region, whereas the ovary forms follicles mainly in the cortical region. The medullary region in the ovary exhibits morphological and functional diversity among mammalian species that ranges from ovary-like to testis-like characteristics. This review focuses on the mechanism of gonadal sex differentiation along the cortical-medullary axis and compares the features of the cortical and medullary regions of the ovary in mammalian species.

Partial male-to-female reprogramming of mouse fetal testis by Sertoli cell ablation

“…In ovarian primary sex cords, supporting cells do not express Sry / Sox9 ( Albrecht and Eicher, 2001 ), but do express Foxl2 , an ovary-determining factor in goat, at E12.0-12.5 in mice ( Boulanger et al, 2014 ; Schmidt et al, 2004 ). These FOXL2-positive cells are mitotically arrested pre-granulosa cells ( Gustin et al, 2016 ; Mork et al, 2012 ) that contribute to the first wave of folliculogenesis soon after birth (see review by Imaimatsu et al, 2022 ; Suzuki et al, 2015 ). In fetal ovaries at E12.5 and thereafter, the surface epithelia continuously undergo proliferation, ingression and expansion into the subepithelial region ( Mork et al, 2012 ; Rastetter et al, 2014 ), leading to the formation of FOXL2-positive ovarian cords (also known as ‘ovigerous’ or ‘secondary sex’ cords) throughout the late fetal stages ( Ng et al, 2014 ; Niu and Spradling, 2020 ; Rastetter et al, 2014 ; Suzuki et al, 2015 ).…”