Testis-like development of gonads in female moles. New insights on mammalian gonad organogenesis

Abstract

Moles are unique among mammals because all females of several species of genus Talpa have bilateral ovotestes (gonads with both ovarian and testicular tissue). Based on the analysis of a large sample of embryos, foetuses and infants over a 13-year period, we have studied the development of the gonads in male and female moles of the species Talpa occidentalis. Several new field and laboratory procedures were developed specifically to obtain and manage this singular material. Our results reveal that gonads of female moles develop according to a testis-like pattern, which includes cord formation and mesonephric cell migration, and begins at the same time as testis differentiation in males. The first signs of sex differentiation do not appear in males but in females. Female (but not male) gonads are regionalised with a cortex (precursor of the ovarian tissue) and a medulla (precursor of the testicular tissue). Germ cells concentrate only in the cortex, so that the medulla soon becomes sterile. Testicular tissue development is transiently retarded in females for about a week before birth, and resumes afterwards. Development of the ovarian tissue in females is considerably delayed with respect to that of testicular tissue in both males and females. The molecular characterisation of peritubular myoid cells, which are exclusive of testes, evidences the presence of testicular tissue in the gonads of female moles, which also contain Leydig cells. However, the absence of fully differentiated Sertoli cells indicates that these cells are not responsible for triggering the differentiation of such a testicular tissue. Our results are also discussed regarding the definition of Sertoli cell morphology and function, and the possible role of germ cells in the sex-reversal process. Differences observed between XX and XY gonad development in moles suggest that the mammalian testis-determining gene, SRY, has an "anti-regionalisation" role during gonadal development, at least in those mammalian species in which regionalisation of the female gonad occurs.

The spatio-temporal pattern of testis organogenesis in mammals - insights from the mole

“…slowly, throughout a three-day period, from the s4b stage, where the first laminin deposits appear, to the s5b stage, where testis cords are histologically recognizable for the first time, as described previously (Barrionuevo et al, 2004a). Immunofluorescence images of Sertoli cell markers in the mole (SF1, SOX9, AMH and DMRT1) reveal structures resembling cords in s5a testes, although at this stage, testis cords are not yet histologically defined.…”

“…In the mouse, the tunica albuginea begins to form at 12.5 dpc, once the testis cords have organized (Karl and Capel, 1998). In the mole, morphological differentiation of the tunica albuginea occurs between s6 and s8 stages (Barrionuevo et al, 2004a), but in the present paper we report that the process begins one day earlier, at the s5c stage. This process involves mainly the production of collagen fibres and the differentiation of the cells forming the basement membrane layer underlying the coelomic epithelium, which flatten and dispose parallel to the surface epithelium.…”

“…As moles do not breed in captivity, embryonic gonad collection required the dissection of wild pregnant female moles. They were captured in poplar groves around Chauchina and Santa Fé (Granada province, southern Spain), as described previously (Barrionuevo et al, 2004a). Captures were made under annual permission granted by the Andalusian Environmental Council.…”

“…Female moles represent the only case of generalized XX true hermaphroditism described so far in mammals, since all of them are fertile despite that they have bilateral ovotestes (gonads with both ovarian and testicular tissue) instead of normal ovaries (Jiménez et al, 1993;Sánchez et al, 1996, Rubenstein et al, 2003. Barrionuevo et al (2004a) studied the gonad development in the Iberian mole, Talpa occidentalis, showing that the testicular portion of the ovotestes in XX moles develops in a testis-like pattern. Genital ridges are detectable at the s4 stage of mole development (corresponding to 14-16 dpc; Barrionuevo et al, 2004b; the entire gestation length in this species is 28 days), and testicular cords are first observed at the s5b stage (18 dpc) in both males and females.…”

Retinal development and function in a ‘blind’ mole

“…(a) Material analysed Ninety-seven specimens of T. occidentalis were obtained from animals captured in the wild as described previously (Barrionuevo et al 2004a) under permission granted by the Andalusian Environmental Council. Developmental stages were determined according to Barrionuevo et al (2004b) and Carmona et al (2009).…”