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

Abstract

Recent studies on mice with mutations in the Clock gene have shown that this mutation disrupts oestrus cyclicity and interferes with successful pregnancy. In order to determine whether two other molecular components of the main clock, namely the period genes, Per1 and Per2, have an effect on the length of the oestrous cycle and the reproductive success, we used Per1-and Per2-deficient females. We show that although fecundity of young adult Per mutant females does not differ from that of wild-type females, middle-aged Per mutant mice are characterised by lower reproductive success than the control group. This may be a consequence of irregularity and acyclicity of the oestrous cycle of the middle-aged mutants. Besides, we demonstrate that Per mutant females have significantly more embryonal implantations in the uterus than successfully delivered offspring. The reproductive deficits of the middle-aged Per mutant females are comparable with those seen in aged wild-type mice. This suggests that Per1 and Per2 mutations cause an advanced ageing.Reproduction (2008) 135 559-568

The clock genePeriod1regulates innate routine behaviour in mice

“…This is surprising as both female [17] and male (this study; electronic supplementary material, figure S1) Per1 2/2 mice are lighter than their WT controls. Lighter individuals in a given species normally have a higher voice pitch [30,31].…”

“…Deletion of clock genes causes pronounced cognitive and behavioural effects throughout the animal kingdom [41]. Period1-deficient mice display alterations in glucocorticoid rhythmicity [42], addiction [43], muscle strength [44], colonic motility [45], fertility [17,46] and memory [16].…”

“…Evidence for that conjecture comes from altered courtship behaviour in Per-mutant male fruitflies (Drosophila melanogaster) [14,47] and the observation of a smaller litter number under homozygous breeding of Per1 2/2 mice [17].…”

Biological rhythms and fertility: the hypothalamus–pituitary–ovary axis

“…66 On the one hand, studies on Per1 or Per2 mutant mice suggested the disruption of circadian rhythms with only minor fertility alterations, such as decreased litter size, increased perinatal mortality, and disruption of the estrus cycle with age. 67,68 In specific, these mutants have normal reproductive function, but fertility rapidly deteriorates with age. In Per1/Per2 null mice, Pilorz and Steinlechner found similar fecundity as in wild type in young adult, but there was lower reproductive success because of the low number of successfully delivered offspring in middleaged mice.…”

“…In Per1/Per2 null mice, Pilorz and Steinlechner found similar fecundity as in wild type in young adult, but there was lower reproductive success because of the low number of successfully delivered offspring in middleaged mice. 68 On the other hand, mice deficient in Cry1 or Cry2 have accelerated agerelated decline in fertility, as judged by the pregnancy rates in comparison with agematched wildtype mice, but it was rescued by the adjustment of the light-dark cycles to match with the endogenous circadian rhythms. 69 The effects of environmental perturbations and conse quent disruption of circadian clock on reproductive function have tested as well.…”