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

Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years and is predominantly idiopathic. A transgenic mouse model of follicular POI, the Double Mutant (DM), are fertile at 6-weeks of age, become infertile by 9-weeks and exhibit POI by 3-months. DM female mice generate oocytes lack...

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Bibliographic Details
Main Authors: Kaune, H, Williams, S, Sheikh, S
Format: Journal article
Published: CSIRO Publishing 2016
Description
Summary:Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years and is predominantly idiopathic. A transgenic mouse model of follicular POI, the Double Mutant (DM), 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 <i>O</i>-glycans and complex <i>N</i>-glycans due to deletion of <i>C1galt1</i> and <i>Mgat1</i> respectively (DM: <i>C1galt1</i><sup>F/F</sup><i>Mgat1</i>F/F:ZP3<i>Cre</i>; Control: <i>C1galt1</i><sup>F/F</sup><i>Mgat1</i><sup>F/F</sup>). To determine if DM follicle development could be improved in a controlled environment, follicles from DM and Controls were cultured individually and follicle growth, morphology, survival and antrum formation were evaluated. DM ovaries were more rigid than Control at 3-, 6- and 9-weeks which was exacerbated with age resulting in a failure to isolate follicles from 9-week DM females. DM follicles had decreased survival compared to Control follicles from females at 3- and 6-weeks. 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 Controls. In conclusion, a population of DM follicles retain the potential to develop <i>in vitro</i> and therefore follicle culture offers a reliable method to generate antral follicles from preantral after the onset of POI in these females.