Ovarian hypercytolipidemia induced by obese (ob/ob) and diabetes (db/db) mutations: basis of female reproductive tract involution II

The diabetes (db/db) and obese (ob/ob) genotype mutations induce a progressive, hypercytolipidemic condition within the ovarian compartments of the female reproductive tract that results in sterility and premature organ involution in C57BL/KsJ mice. The current studies focus on the ultrastructural changes that occur within the ovarian interstitial, thecal, and follicular granulosa cell layers during the progressive expression of these mutations which promote tissue cytolipidemia-induced organoinvolution. Control (normal: +/?), diabetes (db/db), and obese (ob/ob) genotype groups were prepared for high resolution light (HRLM) and transmission electron microscopic (TEM) analysis of ovarian tissue samples collected from 4 (young)- to 20 (aged)-week-old mice, allowing for the progressive influences of the mutational aberrations on tissue structure to be evaluated. Compared to controls, both (ob/ob) and (db/db) mutations induced a dramatic increase in ovarian interstitial, thecal and follicular granulosa cytolipid vacuole accumulations, which increased in density between 4 and 20 weeks of age. Initially, lipid vacuoles aggregated in the interstitial and thecal regions of ovarian follicles in response to the hyperglycemic-hypertriglyceridemic metabolic conditions typical of both (ob/ob) and (db/db) groups. Progressive cytoplasmic movement of the lipid pools established a perinuclear isolation from associated cytoplasmic organelles. Progressive lipid accumulations forced cytoplasmic organelles to peripheral cell compartments and altered the follicular cell profile towards that of adipocyte-like entities relative to controls. The progressive hypercytolipidemia-induced alterations in cell structure disrupted normal tissue continuity, which culminated in premature ovarian organo-involution and female reproductive sterility. (C) 2004 Elsevier Ltd. All rights reserved.