Short oestrous cycles in sheep during anoestrus involve defects in progesterone biosynthesis and luteal neovascularisation
Résumé
Anoestrous ewes can be induced to ovulate by the socio-sexual, 'ram effect'. However, in some ewes the induced ovulation is followed by an abnormally short luteal phase causing a so called, "short cycle". The defect responsible for this luteal dysfunction has not been identified. In this experiment we investigated ovarian and uterine factors implicated in male-induced short cycles in anoestrus ewes using a combined endocrine and molecular strategy. Prior to ovulation, we were able to detect a moderate loss of thecal expression of steroid acute regulatory protein (STAR) in ewes that had not received progesterone priming (which prevents short cycles). At and following ovulation we were able to identify significant loss of expression of genes coding key proteins involved in the biosynthesis of progesterone (STAR, CYP11A1, HSD3B) as well as genes coding proteins critical for vascular development during early luteal development (VEGFA, VEGFR2) suggesting dysfunction in at least two pathways critical for normal luteal function. Furthermore, these changes were associated with a significant reduction of progesterone production and luteal weight. Additionally, we cast doubt on the proposed uterine-mediated effect of prostaglandin F2α as a cause of short cycles by demonstrating both the dysregulation of luteal expression of the PGF receptor, which mediates the luteal effects of PGF2α, and by finding no significant changes in the circulating concentrations of PGFM, the principal metabolite of PGF2α in ewes with short cycles. This study is the first of its kind to examine concurrently, the endocrine and molecular events in the follicular and early luteal stages of the short cycle.