Analysis of in vitro follicle development during the onset of premature ovarian insufficiency in a mouse model

Abstract

Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years of age and is predominantly idiopathic. In a transgenic mouse model of follicular POI, the Double Mutant (DM), female mice are fertile at 6 weeks of age, become infertile by 9 weeks and exhibit POI by 3 months. DM female mice generate oocytes lacking mucin O-glycans and complex N-glycans due to deletion of core 1 synthase, glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1galt1) and mannoside acetylglucosaminyltransferase 1 (Mgat1) respectively (DM, C1galt1F/FMgat1F/F:ZP3Cre; Control, C1galt1F/FMgat1F/F). To determine whether DM follicle development could be improved in a controlled environment, follicles from DM and Control mice were cultured individually and follicle growth, morphology, survival and antrum formation were evaluated. DM ovaries were more rigid than Control ovaries at 3, 6 and 9 weeks, which was exacerbated with age, resulting in a failure to isolate follicles from 9 week-old DM females. DM follicles had decreased survival compared with Control follicles from females at 3 and 6 weeks of age. Furthermore, survival rate of DM follicles decreased with age between 3 and 6 weeks. DM follicles at both 3 and 6 weeks had accelerated follicle growth and altered antrum formation during the first few days of culture but, after 6 days, follicles were equivalent in size to the Controls. In conclusion, a population of DM follicles retain the potential to develop in vitro, and therefore follicle culture offers a reliable method to generate antral follicles from preantral follicles after the onset of POI in these female mice.