The Clock mutation reduces reproductive performance of mice by affecting the implantation capacity: Maternal Clock...

Here, we showed that the Clock gene was important for reproductive performance in mice. We compared outcomes from the four possible mating combinations between wild-type mice (WT) and mice homozygous for the Clock delta-19 mutation (CL). We found that the only significant differences were between the WT♂ × WT♀ and CL♂ × CL♀ mating groups; these groups differed with regard to elongation of the pregnancy period (19.3 vs. 20.5 days, respectively, P < 0.05) and the number of newborn pups (13.4 ± 0.8 vs. 8.6 ± 1.5, respectively, P < 0.05). Because CL dams impregnated by male CLs exhibited normal continuous increases in body weight during the entire gestation period and did not show any signs of spontaneous abortion from mid to late gestation, we reasoned that some embryos were lost before or at the time of implantation. Immediately before implantation (88 hours after fertilization), neither the number of embryos collected from uteri nor the percentage of the embryos that reached the blastocyst stage differed significantly among mating groups. In contrast, immediately after implantation (160 hours after fertilization), the average number of implantation sites was significantly lower for the CL♂ × CL♀ mating group than that for the WT♂ × WT♀ mating group (7.0 vs. 13.0, P < 0.05); this decrease was accompanied by a significant lowering of the positions of implantation sites in uteri, and this lowering of the implantation sites was more severe when mothers and embryos bore more CL alleles (WT♂ × WT♀ >CL♂ × WT♀ > WT♂ × CL♀ >CL♂ × CL♀), suggesting that the Clock mutation reduced the reproduction performance of the parents by affecting the implantation capacity via such as embryos' ability to implant.