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Hum. Reprod. Advance Access originally published online on October 6, 2005
Human Reproduction 2006 21(1):68-79; doi:10.1093/humrep/dei313
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Developmental and reproductive performance in circadian mutant mice

H. Dolatshad1, E.A. Campbell1, L. O’Hara1, E.S. Maywood2, M.H. Hastings2 and M.H. Johnson1,3

1 Department of Anatomy, Downing Street, Cambridge CB2 3DY, UK and 2 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

3 To whom correspondence should be addressed. E-mail: mhj{at}mole.bio.cam.ac.uk

BACKGROUND: Genes underlying circadian rhythm generation are expressed in many tissues. We explore a role for circadian rhythms in the timing and efficacy of mouse reproduction and development using a genetic approach. METHODS: We compare fecundity in ClockD19 mutant mice (a dominant-negative protein essential for circadian rhythm activity) and in Vipr2–/– null mutant mice (affecting the generation and output of the circadian rhythm of the hypothalamic suprachiasmatic nucleus) with wild type (WT) litter mates under both a 12 h:12 h light:dark cycle and continuous darkness. RESULTS: Uteri from ClockD19 mice show no circadian rhythm and Vipr2–/– mice show a phase-advanced rhythm compared to WT uteri. In neither mutant line were homozygous or heterozygous fetuses lethal. Sexually mature adults of both mutant lines showed mildly reduced male in vivo (but not in vitro) fertility and irregular estrous cycles exacerbated by continuous darkness. However, pregnancy rates and neonatal litter sizes were not affected. The ClockD19 mutant line was distinguishable from the Vipr2–/– null mutant line in showing more peri-natal delivery problems and very poor survival of offspring to weaning. CONCLUSIONS: A fully functional central and peripheral circadian clock is not essential for reproduction and development to term, but has critical roles peri-natally and post-partum.

Key words: circadian rhythm/clock mutants/fecundity/mice/uterus


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