Oral Presentation The International Congress of Neuroendocrinology 2014

Kisspeptin signalling is required to maintain Progesterone levels during mouse pregnancy. (#79)

William H Colledge 1 , Victoria Kyle 1 , Shel H Yeo 1 , Alice Herreboudt 1
  1. Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Kisspeptin neuropeptides are encoded by the Kiss1 gene and directly stimulate GnRH neurons via the G-protein coupled receptor, GPR54. Kiss1 or Gpr54 mutant mice have hypogonadotrophic hypogonadism caused by a failure to secrete GnRH. The aim of this study was to determine whether the sterility of mutant female mice was solely caused by absence of central kisspeptin signalling or whether there are additional defects in the ovaries. To study this, we used a hormone replacement protocol to mature the reproductive axis of the mutant mice and breed these with fertile males. Although, the mutant mice were induced to ovulate, none of the mice maintained pregnancy past E6.5 of gestation. It was found that the mutant mice had significantly lower levels of progesterone compared to wild-type pregnant mice. qRT-PCR indicated reduced expression of transcripts involved in the progesterone biosynthetic pathway in the mutant ovaries. Ovary transplantation studies showed that mutant ovaries implanted into wild-type mice could support pregnancy to term indicating that there was no intrinsic defect in the mutant ovaries. Progesterone replacement allowed pregnancy to progress normally past E6.5. We hypothesise that the failure of the mutant mice to maintain progesterone levels during pregnancy is caused by inadequate luteotrophic stimulation of the corpus luteum due to central kisspeptin signalling defects.