title: MRL/MpJ-Fas(lpr) mice show abnormalities in ovarian function and morphology with the progression of autoimmune disease.
abstract: The immune system is known to affect reproductive function, and maternal-fetal immune tolerance is essential for a successful pregnancy. To investigate the relationship between autoimmune disease and female reproductive function, we performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice, autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas(lpr) (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset. Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice of the other two strains, respectively. Histological analysis at 3 months revealed that the number of primordial follicles was smaller in MRL-background mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months, and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months, respectively. In particular, MRL/lpr mice showed numerous infiltrating lymphocytes within the ovarian interstitia, and partially stratified ovarian surface epithelia with more developed microvilli than that observed in C57BL/6 mice at 6 months. No significant differences in serum hormone levels were observed between the strains. In conclusion, MRL/lpr mice display altered ovarian development, morphology and function consistent with the progression of severe autoimmune disease, as these findings are less severe in MRL/+ counterparts.
authors: a Laboratory of Anatomy, Department of Biomedical Sciences , Graduate School of Veterinary Medicine, Hokkaido University , Sapporo , Japan and.
authors: Yuki
authors: Y
authors: Otani
authors: Osamu
authors: O
authors: Ichii
authors: Saori
authors: S
authors: Otsuka-Kanazawa
authors: Masataka
authors: M
authors: Chihara
authors: Teppei
authors: T
authors: Nakamura
authors: Yasuhiro
authors: Y
authors: Kon
mesh_terms: D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D030762:Estrous Cycle / Q000235:genetics / Q000276:immunology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009154:Mutation; D010053:Ovary / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D012741:Sexual Maturation / Q000235:genetics / Q000276:immunology; D013739:Testosterone / Q000097:blood; D019014:fas Receptor / Q000235:genetics
chemical_list: D019014:fas Receptor; D013739:Testosterone; D005640:Follicle Stimulating Hormone
keywords: MRL/lpr mice; autoimmune disease; estrous cycle; ovarian reserve; ovary