Estrogen actions on follicle formation and early follicle development.
Estradiol-17beta (E(2)) affects late follicular development, whereas primordial follicle differentiation and early activation are believed to be independent of E(2). To test this hypothesis we compared numbers of primordial and primary follicles in wild-type and E(2)-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 E(2) 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 E(2) treatment, suggesting that E(2) 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. E(2) treatment restored the ovarian follicular morphology in ArKO mice, and consequently the immunostaining patterns, but had no effect on early follicle numbers. In conclusion, E(2) has a role in controlling the size of the oocyte and primordial follicle pool in mice.
Prince Henry's Institute of Medical Research, Monash Medical Centre Clayton, Block E, Level 4, Clayton, VIC 3168, Australia. kara.britt@phimr.monash.edu.au
Kara L
KL
Britt
Philippa K
PK
Saunders
Stephen J
SJ
McPherson
Marie L
ML
Misso
Evan R
ER
Simpson
Jock K
JK
Findlay
D000818:Animals; D054304:Anti-Mullerian Hormone; D001141:Aromatase / Q000172:deficiency / Q000235:genetics; D055430:Bone Morphogenetic Protein 15; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000378:metabolism; D004958:Estradiol / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D055429:Growth Differentiation Factor 9; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology; D006080:Ovarian Follicle / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D013735:Testicular Hormones / Q000378:metabolism
C525901:BMP15 protein, human; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C525897:GDF9 protein, human; C525898:Gdf9 protein, mouse; D006023:Glycoproteins; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D013735:Testicular Hormones; C419554:WTAP protein, human; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D001141:Aromatase