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Comparison of Reproductive Function in Female TgMISIIR‑TAg Transgenic and Wildtype C57BL/6 Mice.

Comparative Medicine 2018 December 28
Transgenic TgMISIIR-TAg (TAg) mice express the oncogenic virus SV40 in Mullerian epithelial cells. Female TAg micespontaneously develop epithelial ovarian carcinoma, the most common type of ovarian cancer in women. Female TAg miceare infertile, but the reason has not been determined. We therefore investigated whether female TAg mice undergo puberty,demonstrate follicular development, maintain regular cycles, and ovulate. Ovarian cancers in women commonly develop aftermenopause. The occupational chemical 4-vinylcyclohexene diepoxide (VCD) accelerates follicle degeneration in the ovariesof rats and mice, causing early ovarian failure. We therefore used VCD dosing of mice to develop an animal model for menopause.The purpose of this study was to characterize reproductive parameters in female TAg mice and to investigate whetherthe onset of ovarian failure due VCD dosing differed between female TAg and WT C57BL/6 mice. As in WT female mice, TAgfemale mice underwent puberty (vaginal opening) and developed cyclicity in patterns that were similar between the groups.Vehicle-only TAg mice had fewer ovulations (numbers of corpora lutea) than WT animals. VCD exposure delayed the onsetof puberty (day of first estrus) in TAg as compared with WT mice. Morphologic evaluation of ovaries revealed many moredegenerating follicles in TAg mice than WT mice, and more VCD-dosed TAg mice were in ovarian failure than VCD-dosedWT mice. These results suggest that despite showing similar onset of sexual maturation, TAg mice have increased folliculardegeneration and fewer ovulations than WT. These features may contribute to the inability of female TAg mice to reproduce.

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