Developmental and reproductive performance in circadian mutant mice

Abstract

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.

Low reproductive success in Per1 and Per2 mutant mouse females due to accelerated ageing?

“…Therefore, it is important to bear in mind that genetic divergences may occur in the successive generations. Ideally, to make comparisons in inbred mouse strains, it is advantageous to use litter mates (Dolatshad et al 2006). In the present study, however, we were not able to use litter mates.…”

“…This regularity in oestrus cyclicity provides a hint for the regularity in the rhythmicity of the luteinizing hormone (LH) surge and ovarian hormones facilitating fertility and embryonal development (Day et al 1989, Diaz et al 2000, Wise et al 2002, Miller et al 2004, Nelson 2005. Contrary to this, adult Clock mutant females reveal prolonged irregular cycles associated with elevated rates of foetal reabsorption and pregnancy failures (Miller et al 2004, Kennaway 2005, Dolatshad et al 2006. The oestrous cycle defects in Clock mutants have been explained by disruption in the timing or coordination of gonadotrophin-releasing hormone release and thus of LH surge on prooestrus leading to reduced levels of oestrogen and progesterone (Miller et al 2004).…”

“…As the second Reproductive success in Per mutant mouse females best choice, we used backcrossed wild-type females consisting of B6 and 129S7 as controls for the Per mutants with the same background. The recent studies on Clock mutant females (Miller et al 2004, Dolatshad et al 2006 revealed discrepancies with regard to the light condition at which the pregnancy failures occur. Miller et al (2004) have demonstrated that Clock mutant females show irregularities in oestrus cyclicity and foetal resorption under LD conditions.…”

“…Reproduction is one of the most important factors enabling the animal to optimise its biological efficiency and hence its fitness. The secretion of sex hormones that regulate reproductive functions, such as oestrous cycle, pregnancy and lactation, is characterised by rhythms coordinating these functions so that they occur at the most advantageous time (Turek & Van Cauter 1994, Johnson & Day 2000, Kennaway 2005, Dolatshad et al 2006. This rhythmic behaviour of pregnant and lactating females also forms the cyclic environment for foetuses and neonates before their development enables photic entrainment of the circadian pacemaker (Weaver & Reppert 1995).…”

“…Specific changes in the molecular function in the SCN, e.g. mutation of Clock in mice have caused a disrupted oestrous cyclicity and poor reproductive outcome associated with increased foetal absorption during pregnancy and high pregnancy failure (Kennaway 2005, Dolatshad et al 2006, Hoshino et al 2006. Clock mutations may even affect negatively the growth of pups (Miller et al 2004).…”