Genotypic influences on reproductive aging of inbred female mice: effects of H-2 and non-H-2 alleles

The H-2 (major histocompatibility) complex of mice influences a variety of physiologic parameters. This study describes the influences of H-2 polymorphisms and other genetic influences on age-related changes (5-20 mo) in estrous cycles and fecundity. We monitored estrous cycles of virgin or retired-breeder mice of congenic strains on the background of C57BL/10Sn (B10):B10.BR/Sg (B10.BR) and B10.RIII/Sn (B10.RIII). For another comparison, we examined the C57BL/6J (B6) strain, which has the same H-2 haplotype as the B10. Estrous cycles were categorized by length during 10 mo of observations. From 5 to 15 mo of age, B10 and B10.RIII mice displayed a preponderance of 5-day cycles, B10.BR mice displayed a preponderance of 4-day cycles, and B6 mice had diminishing numbers of 4-day cycles. Age-related acyclicity differed with strain, particularly among retired breeders; B6 mice had an earlier onset and more rapid increase of acyclicity with age than the B10 congenic mice. Litters/female, maternal age at last litter, and total pups/female differed with strain; B10.BR and B10.RIII were similar and both had greater values than B10 mice. In conclusion, reproductive senescence of female mice was influenced by genes at the H-2 locus and elsewhere.