Reproduction Abstracts

Premature ovarian failure (POF) affects ~1% of women over 40 and is idiopathic in 74–90% of cases. A transgenic mouse model of POF has been generated (known as double mutant; DM) resulting from oocyte-specific deletion of two glycosyltransferases. Glycoproteins from DM oocytes lack complex O- and N-glycans. DM females are fertile at 6-weeks, infertile by 9-weeks and exhibit POF by 12-weeks of age with follicle depletion, elevated gonadotropins and decreased sex steroids. To identify possible genetic pathways involved in the onset of POF, we analysed Control and DM ovary transcriptomes at 3-, 6- and 9-weeks of age. Ovaries were collected and pooled in triplicates (n=3 per group; three groups), total RNA extracted and whole-genome expression profile carried out using Illumina arrays. Data analysis was performed using R. A total number of 21 007 probes were assessed and differentially expressed genes detected at 9-weeks were analysed for functional enrichment using DAVID. Transcriptomic analysis of DM ovaries demonstrated a sharp change in gene expression compared with Controls from 3- to 9-weeks. In DM ovaries, only two genes were detected as differentially expressed at 3-weeks (Snrpa; down-regulated and Ctsk; up-regulated) and three more genes at 6-weeks (Kntc1, Dppa5a and RIKENcDNA E330017A01; all of them downregulated) which could represent candidate gene regulators for the onset of POF in the DM. A total of 1253 genes were differentially expressed at 9-weeks in DM ovaries. Up-regulated genes were preferentially enriched for cell communication and extracellular matrix, representing potential pathways affecting ovarian function and impairing fertility capacity.