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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P026 | DOI: 10.1530/repabs.1.P026

Kisspeptin signalling is required to maintain progesterone levels during mouse pregnancy

William H Colledge, Xavier d’Anglemont de Tassigny, Shel-Hwa Yeo, Victoria Kyle & Alice Herreboudt


University of Cambridge, Cambridge, UK.


Kisspeptin neuropeptides stimulate release of GnRH to maintain mammalian fertility. Kisspeptins are encoded by the Kiss1 gene and directly stimulate GnRH neurons via the G-protein coupled receptor54 (GPR54). Transgenic mice with inactivating mutations of Kiss1 or Gpr54 are sterile and have underdeveloped gonads (hypogonadism) and low GnRH levels 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 Kiss1 mutant female mice and applied a hormone replacement regime to mature the reproductive axis and induce ovulation. These mutant mice were bred with fertile males and evaluated for maintenance of pregnancy. Although, the mutant mice could ovulate and fertilized eggs develop into blastocysts and implant into the uterus, none of the mutant female mice maintained pregnancy past E6.5. It was found that the mutant mice had significantly lower levels of progesterone at E10.5 compared to WT pregnant mice. Ovary transplantation studies showed that mutant ovaries implanted into WT mice could support pregnancy to term indicating that there was no intrinsic defect in the mutant ovaries. Progesterone replacement allowed pregnancy to proceed normally up to E10.5. 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 at the level of the GnRH neuron. This work was funded by a BBSRC Case Award (BB/FO1936X/1).

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