Fertility study of complement-3 in mice

Abstract

Human oviductal cells produce complement-3 (C3) and its embryotrophic derivative, iC3b in the presence of embryos. We proposed that C3-deficiency would lead to fertility impairment in mice in vivo. To determine the physiological significance of this protein in reproduction, heterozygous mice carrying the mutated C3 gene (C57BL/6J-C3tmlCrr) were purchased from Jackson Laboratory. Crossing of these mice (C3+/-) generated mice carrying the homozygous (C3+/+) and mutated C3 (C3-/-) genes. C3-/- and the wild type C3+/+ were allowed to cage with males of the same genotype for 6 months and their fertility was examined. Both genotypes are fertile and produce viable pups. The number of litters per week born from C3-/- pairs (0.116±0.05) were significantly smaller than those in C3 +/+ pairs (0.168±0.04). There were no significant difference between the mean numbers of pups per litter, mean born weight and mean litter size at wean between the two groups. However, the mean pup weight at weaning of C3 -/- pairs (8.1± 1.2 g .) was significantly smaller than that of C3 +/+ pairs (8.6±1.3 g). Although C3 protein could not be detected in the C3 -/- mice serum by Western blot, C3 immunoreactivity and mRNA was detected in the oviduct and liver tissues homogenate, suggesting the presence of mutated C3 molecules in these animals. These mating results suggested that the C3 -/- mice require longer getting pregnant and the resulting pups are smaller in size at weaning. The biological activity of the mutated C3 molecule on embryo development remains to be investigated.