Ovarian Organogenesis in Mammals: Mice Cannot Tell Us Everything

Abstract

The mammalian ovary shows extensive variation mainly in relation to the interstitial tissue of the ovary, the so-called interstitial gland, and the degree of gonad regionalisation, which implies the existence of a cortex and a medulla. Three mammalian species, mouse, human, and mole, have been reviewed here as representative animal models for ovarian variability. Whereas the human ovary may be considered to have a conventional pattern of development, the mouse and the mole represent the two extremes of the variation range. The mouse is exceptional among mammals because ovarian regionalisation is much less relevant than in other species. Contrarily, the mole ovary is very similar to that of humans regarding the cortical region, but shows a testis-like pattern of development in the medullary region. Thus, the mole ovary is in fact an ovotestis, a phenomenon also described in other mammals. Accordingly, current studies on the development of the mouse ovary are not sufficient to understand the process in a more general context, because ovarian organogenesis is exceptionally simple in the mouse. From an evolutionary perspective, mammals show a tendency to eliminate or reduce gonad regionalisation, in contrast with the situation in other vertebrates, where this trait has been preserved. Since developmental variants may not be associated with particular taxonomic groups, their origin seems to be adaptive rather than phylogenetic. The demonstration that gonad development is a rather plastic process in mammals helps to explain how some mammals could have evolved towards more primitive gonad developmental models in response to selective pressure.

A MicroRNA (mmu-miR-124) Prevents Sox9 Expression in Developing Mouse Ovarian Cells1

“…In situ hybridization studies showed that miR-124 is present mainly in the cortical region of the female gonad at 13.5 dpc (i.e., the portion from which the ovarian tissue mostly develops in mammals and other vertebrates [48] and also the region in which the complete inhibition of Sox9 would be especially necessary in the differentiating female gonad. The fact that Sox9 is expressed mainly in the medulla of the developing testis is not a valid argument against this hypothesis because this is not the case in developing ovaries, where Sry is absent and, thus, Sox9 is not up-regulated anywhere.…”

Identification of Novel Markers of Mouse Fetal Ovary Development

“…The ovary in many species, including most vertebrates, is regionalized into a highly vascularised medulla and a cortical region in which the germ cells reside [67]. In mouse, this regionalization is not obvious at a morphological level until shortly before birth.…”

Genetic Control of Ovarian Development

“…Additionally, mice with inducible gonad-specific Cre recombinases should permit the re-examining of the previously known genes that have already been implicated in sexual development, for example, in cases where the null phenotypes show defects in gonad formation, rather than subsequent sexual differentiation. Still, even the most ardent murine aficionado has to keep the perspective that mice cannot tell us everything about ovarian organogenesis in other species, including humans [Jimenez, 2009]. Here too, whole genome sequencing technologies are bound to uncover novel sex determination genes in patients with DSD [Arboleda and Vilain, 2011].…”