VCD-induced model of menopause

Preconditioned Models Shipped Ready for Your Study

This service produces mouse models of human perimenopause to help reveal the genetic and physiological dynamics that influence women's susceptibility to age-related, chronic, and cumulative diseases, such as heart disease, diabetes, cancer, osteoporosis, and stroke.

The only inducible rodent models currently available for modeling menopausal transition are ovariectomized (OVX) rats and mice. However, almost 90% of menopausal women still have their ovaries. Our service uses the industrial chemical 4-vinylcyclohexene diepoxide (VCD) to selectively accelerate the natural loss of small primordial and primary follicles without affecting other tissues, including the rest of the ovary, resulting in an endocrine state that more closely mimics the human menopausal transition. It is based on a method developed by collaborators Drs. Loretta Mayer and Patricia Hoyer at the University of Arizona, College of Medicine (Mayer et al. 2002).

comparison chart
Fig. 1. Cyclicity, estrogen levels, and FSH levels are similar in VCD-induced mouse and human menopause. The OVX mouse begins menopause quickly and skips peri-menopause, typically 1 to 10 years before human menstrual cycle cease (post-menopause refers to the year after peri-menopause). Values for VCD-induced menopause are relative to the beginning of the 15-day VCD injection protocol.

The method developed by Mayer and Hoyer is particularly valuable because it can be applied to most mouse strains, including models of atherosclerosis, osteoporosis, diabetes, Alzheimer's, cancer, and other diseases common among menopausal women. For example, a recent study by the two scientists and their colleagues showed that 17beta-estradiol suppression of atherosclerosis in low-density lipoprotein (Ldlr) knockout mice B6.129S7-Ldlrtm1Her/J (002207) is more effective in VCD-treated mice than in similarly treated ovariectomized mice (Mayer et al. 2005). These results underscore both the value of the method and the importance of selecting the most research-appropriate mouse model.

JAX® Services in Bar Harbor offers the VCD-induced menopause model on at least 5 genetic backgrounds: C57BL/6J (000664), an atherosclerosis-susceptible strain; C3H/HeJ (000659), an atherosclerosis-resistant strain; B6.129S7-Ldlrtm1Her/J (002207), a strain with normally high serum cholesterol levels and extremely high levels when fed an atherogenic diet; B6.129P2-Apoetm1Unc/J (002052), another strain with high serum cholesterol levels; and NZBWF1/J (100008), a model of systemic lupus erythematosus. For additional cost, this service can be adapted to other strains.

A study recently conducted by our Animal Husbandry and Performance Group demonstrated the efficacy of VCD-induced menopause in these strains.

Number of follicles in VCD-treated (n=10) vs. control (n=10) females at 22, 37, and 51 days from start of treatment. 4-week old females from each strain were given IP injections containing 160 mg/kg of VCD daily, 5 days a week, for 3 weeks. Controls from each strain were injected with vehicle (sesame seed oil) only.

Print-Friendly VCD-Induced Model of Menopaus brochure (pdf)

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References

Mayer LP, Dyer CA, Eastgard RL, Hoyer PB, Banka CL. 2005. Atherosclerotic lesion development in a nove ovary-intact mouse model of perimenopause. Arterioscler Thromb Vasc Biol 25:1910-16.

Mayer LP, Pearsall NA, Christian PJ, Devine PJ, Payne CM, McCusskey MK, Marion SL, Sipes IG, Hoyer, PB. 2002. Long-term effects of ovarian follicular depletion in rats by 4-vinylcyclohexene diepoxide. Repro Tox 16:775-81.