Defects in the first wave of folliculogenesis in mouse XO ovaries

Abstract

In mouse ovaries, the first wave of folliculogenesis perinatally starts near the medullary region, which directs the initial round of follicular growth soon after birth. At the same time, cortical primordial follicles start forming in the ovarian surface region, and then some are cyclically recruited for the second and subsequent rounds of follicular growth. Recent studies suggest different dynamics between the first and subsequent waves of follicular growth in postnatal ovaries. However, the phenotypic differences between these phases remain unclear. Here, we show direct evidence that XO female mice, a murine model for Turner Syndrome, lack the first wave of folliculogenesis. Our histopathological analyses of XX and XO littermates revealed a lack of anti-Müllerian hormone (AMH)-positive primary follicles in the XO ovaries by 4 days post partum (dpp). This loss of first follicles was also confirmed by histological bioassay for SRY-dependent SOX9 inducibility, a specific marker for the first follicular granulosa cells. In contrast, cortical primordial follicles formed properly in XO ovaries, and some of them formed primary and secondary follicles in the subcortical region by 7 dpp. They rapidly developed into late antral follicles, showing similarities to XX littermate ovaries by 21 dpp. These results suggest distinct X-monosomy effects between the first and subsequent waves of follicular growth, highlighting the high susceptibility to elimination of XO oocytes in the first wave of mammalian folliculogenesis.

Role of the X and Y Chromosomes in the Female Germ Cell Line Development in the Mouse (Mus musculus)

“…data]. In agreement with this conclusion, similar selective oocyte loss in the medullary region has been reported in the XO ovary on the B6 genetic background [Miura et al, 2017].…”

Expression of sirtuins in ovarian follicles of postnatal mice

“…There were many secondary follicles in 10‐day postnatal ovaries and the follicle antrum has not yet appeared in the ovaries at this time (Brown, Dunning, Robker, Pritchard, & Russell, 2006). Also, the secondary follicles developed to the late stage of antral follicles in the ovaries of 21d postnatal mice (Miura et al, 2017). By using PMSG to treat 21‐day‐old mice for 48 h, the follicles developed into mature pre‐ovulatory follicles in the ovary.…”

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

“…Some reports suggest that the sex of the primary sex cords and the medullary region is more inclined towards the male phenotype. AMH is expressed in the primary sex cords in the XX gonad, but they are absent from the secondary sex cords that correspond to the cortical region in the differentiated ovary [ 154 ]. The transient and forced expression of SRY in the ovary using heat-shock-inducible SRY in transgenic mouse experiments [ 47 ] led to SOX9 expression in granulosa cells of the first-wave follicles in the medullary region [ 91 ].…”

“…The transient and forced expression of SRY in the ovary using heat-shock-inducible SRY in transgenic mouse experiments [ 47 ] led to SOX9 expression in granulosa cells of the first-wave follicles in the medullary region [ 91 ]. In contrast, forced SRY induction could not induce SOX9-positive cells in the medullary region of the ovaries of XO female mice, in which first-wave follicles were absent [ 154 ]. These data indicate the presence of male-inclined features of the primary sex cords and the medullary region in the ovary and raise the possibility that these features cause or contribute to abnormal masculinization in XX disorders of sexual differentiation in mammals.…”