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Publication : An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene.

First Author  Britt KL Year  2000
Journal  Endocrinology Volume  141
Issue  7 Pages  2614-23
PubMed ID  10875266 Mgi Jnum  J:63458
Mgi Id  MGI:1861029 Doi  10.1210/endo.141.7.7578
Citation  Britt KL, et al. (2000) An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene. Endocrinology 141(7):2614-23
abstractText  With the development of a mouse model of estrogen insufficiency due to targeted disruption of the aromatase gene [the aromatase knockout (ArKO) mouse], a new opportunity exists to examine the role of estrogen in ovarian follicular development. Ovaries and serum were collected from wild-type, heterozygous, and ArKO mice at 10-12 and 21-23 weeks and 1 yr of age. The ovaries were assessed histologically and stereologically, with primary, secondary, and antral follicles and corpora lutea counted. The uteri were hypoestrogenic, and serum levels of LH and FSH in ArKO females were elevated above those in heterozygote and wild-type animals at all ages studied. Although estrogen was not a prerequisite for reinitiation of follicle growth, there was a block of follicular development, and no corpora lutea were present in ArKO ovaries. Thus, the ArKO mouse was infertile as a consequence of disrupted folliculogenesis and a failure to ovulate. Hemorrhagic cystic follicles were present by 21-23 weeks of age. The ovarian phenotype degenerated with age, such that by 1 yr there were no secondary or antral follicles, and the primary follicles present were atretic. Extensive interstitial tissue remodeling occurred, exemplified by an influx of macrophages and collagen deposition, coincident with the loss of follicles. In conclusion, the ovarian environment in ArKO mice does not allow the characteristic development of follicles that culminates in ovulation and demonstrates an in vivo requirement of estrogen for normal ovarian function in the mouse.
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