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BOR - Papers in Press, published online ahead of print July 21, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.028175
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BIOLOGY OF REPRODUCTION 71, 1712–1723 (2004)
DOI: 10.1095/biolreprod.104.028175
© 2004 by the Society for the Study of Reproduction, Inc.


Ovary

Estrogen Actions on Follicle Formation and Early Follicle Development1

Kara L. Britt2,3,4, Philippa K. Saunders5, Stephen J. McPherson6, Marie L. Misso3,4, Evan R. Simpson3, and Jock K. Findlay3

Prince Henry's Institute of Medical Research,3 Department of Biochemistry and Molecular Biology,4 Monash University, Clayton, Victoria 3168, Australia MRC Human Reproductive Sciences Unit,5 Centre for Reproductive Biology, The Chancellors Building, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom Centre for Urological Research,6 Monash Institute of Reproduction and Development, Clayton, Victoria 3168, Australia

Estradiol-17ß (E2) affects late follicular development, whereas primordial follicle differentiation and early activation are believed to be independent of E2. To test this hypothesis we compared numbers of primordial and primary follicles in wild-type and E2-deficient, aromatase knockout (ArKO) mice, and the immunohistochemical staining or mRNA expression of Mullerian inhibiting substance (MIS), Wilms tumor 1 (WT-1), and growth differentiation factor (GDF9), which are 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 wild-type mice on these parameters were also tested. ArKO mice had reduced numbers of primordial and primary follicles compared with wild-type mice (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 with mice of the wild type. There were no differences in the immunostaining of MIS, WT-1, and PCNA in primordial and primary follicles between wild-type and ArKO mice. The only difference was as a consequence of Sertoli and Leydig cells that 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.

1 This work was supported by NH&MRC grants 241000 and 198705 (J.K.F.) and by NIA R37AG08174 (E.R.S.).

2 Correspondence: Kara Britt, Prince Henry's Institute of Medical Research, Monash Medical Centre Clayton, Block E, Level 4, Clayton, VIC 3168, Australia. FAX: 61 3 9594 6125; kara.britt{at}phimr.monash.edu.au




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