The New Zealand obese mouse model of obesity insulin resistance and poor breeding performance: evaluation of ovarian structure and function

Abstract

Infertility, associated with oligo/anovulation, increased ovarian volume, numerous follicular cysts, and metabolic disturbances such as obesity and insulin resistance (IR) are characteristics common to polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age. Here, we show that New Zealand obese (NZO) mice display similar metabolic characteristics such as obesity, leptin insensitivity, glucose intolerance, and IR. Importantly, NZO mice are poor breeders; however, the mechanism for this has not been investigated. The aim of this study was to assess the ovarian structure/morphology and sex hormone levels in female NZO and lean C57BL/6J control mice. Twenty-five NZO and twenty female control mice were studied at three different ages (young, adult, and aged). The animals were weighed, an insulin tolerance test was carried out, and blood was collected for measurement of hormone levels. The ovaries were removed for histological analysis. As expected, NZO mice presented higher body weights (P=0.001), increased basal plasma glucose (P=0.007), and insulin levels (P=0.001) as well as IR, compared with control mice. NZO mice showed an increased ovarian volume, reduced numbers of corpora lutea, and higher total follicle numbers (P=0.0001). The number of primordial follicles increased (P=0.02) at the young stage, as well as the amount of atretic follicles (P=0.03), in NZO compared with control mice. NZO mice also displayed reduced plasma LH and increased estradiol levels. In conclusion, NZO mice show a poor breeding performance due to decreased ovulation, increased number of primordial and atretic follicles, and ovarian size. Given that NZO mice are obese, hyperinsulinemic and insulin resistant, they are suitable for investigating pathophysiological mechanisms linking metabolic alterations with reproductive defects.