The follicle-deplete mouse ovary produces androgen.
The follicle-depleted postmenopausal ovary is enriched in interstitial cells that produce androgens. This study was designed to cause follicle depletion in mice using the industrial chemical, 4-vinylcyclohexene diepoxide (VCD), and characterize the steroidogenic capacity of cells in the residual ovarian tissue. From a dose-finding study, the optimal daily concentration of VCD was determined to be 160 mg/kg. Female B6C3F(1) immature mice were treated daily with vehicle control or VCD (160 mg kg(-1) day(-1), 15 days, i.p.). Ovaries were removed and processed for histological evaluation. On Day 15 following onset of treatment, primordial follicles were depleted and primary follicles were reduced to about 10% of controls. On Day 46, primary follicles were depleted and secondary and antral follicles were reduced to 0.7% and 2.6% of control, respectively. Seventy-five percent of treated mice displayed disruptions in estrous cyclicity. All treated mice were in persistent diestrus (acyclic) by Day 58. Plasma FSH levels were increased (P < 0.05) relative to controls on Day 37 and had plateaued by Day 100. Relative to age-matched cyclic controls, by Day 127, the significant differences in VCD-treated mice included reduced ovarian and uterine weights, elevated plasma LH and FSH, and reduced plasma progesterone and androstenedione. Furthermore, plasma 17beta-estradiol levels were nondetectable. Unlike controls, immunostaining for LH receptor, and the high density lipoprotein receptor (SR-BI), was diffuse in ovarian sections from VCD-treated animals. Ovaries from Day 120 control and VCD-treated animals were dissociated and dispersed cells were placed in culture. Cultured cells from ovaries of VCD-treated animals produced less LH-stimulated progesterone than control cells. Androstenedione production was nondetectable in cells from cyclic control animals. Conversely, cells from VCD-treated animals produced androstenedione that was doubled in the presence of insulin and LH (1 and 3 ng/ml). Collectively, these data demonstrate that VCD-mediated follicle depletion results in residual ovarian tissue that may be analogous to the follicle-deplete postmenopausal ovary. This may serve as a useful animal model to examine the dynamics of follicle loss in women as ovarian senescence ensues.
Department of Physiology, University of Arizona, Tucson, Arizona 85724, USA.
Loretta P
LP
Mayer
Patrick J
PJ
Devine
Cheryl A
CA
Dyer
Patricia B
PB
Hoyer
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000494:pharmacology; D053138:Cyclohexenes; D004195:Disease Models, Animal; D030762:Estrous Cycle; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D006728:Hormones / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D013256:Steroids / Q000096:biosynthesis; D014599:Uterus / Q000473:pathology; D014753:Vinyl Compounds / Q000494:pharmacology
D000728:Androgens; D003510:Cyclohexanes; D053138:Cyclohexenes; D006728:Hormones; D013256:Steroids; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases