Dwarf mice as models for reproductive ageing research

Abstract

Dwarf mice are characterized by extremely long lifespan, delayed ovarian ageing, altered metabolism, lower age-related oxidative damage and cancer incidence rate. Snell dwarf, Ames dwarf and growth hormone receptor knockout mice are three commonly used models. Despite studies focusing on ageing and metabolism, the reproductive features of female dwarf mice have also attracted interest over the last decade. Female Snell and Ames dwarf mice have regular oestrous cycles and ovulation rates, as in normal mice, but with a larger ovarian reserve and delayed ovarian ageing. The primordial follicle reserve in dwarf mice is greater than in normal littermates. Anti-Müllerian hormone (AMH) concentration is seven times higher in Ames dwarf mice than in their normal siblings, and ovarian transcriptomic profiling showed distinctive patterns in older Ames dwarf mice, especially enriched in inflammatory and immune response-related pathways. In addition, microRNA profiles also showed distinctive differences in Ames dwarf mice compared with normal control littermates. This review aims to summarize research progress on dwarf mice as models in the reproductive ageing field. Investigations focusing on the mechanisms of their reserved reproductive ability are much needed and are expected to provide additional molecular biological bases for the clinical practice of reproductive medicine in women.

Keywords: Ames dwarf mice; Folliculogenesis; Growth hormone receptor gene knockout mice; Ovarian ageing; Ovarian reserve; Snell dwarf mice.