Ovary

Estrogen Actions on Follicle Formation and Early Follicle Development

Abstract
Estradiol 17 (E2) affects late follicular development whilst primordial follicle differentiation and early activation are thought to be independent of E2. To test this hypothesis we compared numbers of primordial and primary follicles in wildtype and E2 deficient, Aromatase knockout (ArKO) mice, and the immunohistochemical staining or mRNA expression of Mullerian inhibiting substance (MIS), Wilms tumour 1 (WT-1), and growth differentiation factor (GDF9), known to effect early follicular differentiation. Proliferating cell nuclear antigen (PCNA) staining was a marker of proliferative index. The effects of E2 replacement for 3 wk in 7 wk old ArKO and wildtype mice on these parameters were also tested. ArKO mice had reduced numbers of primordial and primary follicles compared to wildtype (63%, p<0.001 and 60%, p=0.062 respectively). This reduction was not corrected by E2 treatment, suggesting that E2 affects the initial formation or activation of primordial follicles. There was a significant increase in the diameters of the oocytes in primordial follicles of ArKO mice compared to wildtype. There were no differences in the immunostaining of MIS, WT-1 and PCNA in primordial and primary follicles between wildtype and ArKO mice. The only difference was as a consequence of Sertoli and Leydig cells which develop in ovaries of ArKO mice. GDF9 mRNA expression was markedly increased in ArKO ovaries. E2 treatment restored the ovarian follicular morphology in ArKO mice, and consequently the immunostaining patterns, but had no effect on early follicle numbers. In conclusion, E2 has a role in controlling the size of the oocyte and primordial follicle pool in mice.

Key words: Mechanisms of Hormone Action • Ovary • Estradiol • Follicle • Follicular development

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