Prior mating without fertilization increases subsequent litter size in mice

Female exposure to seminal fluid influences multiple aspects of reproductive physiology. We tested the hypothesis that extended exposure to seminal fluid prior to pregnancy provides fertility benefits, as predicted from human studies linking seminal fluid exposure to a reduced incidence of pregnancy disorders. Female mice were co-housed for five months with either vasectomized males (producing seminal plasma but not sperm), vasectomized males without seminal vesicles (producing neither seminal plasma nor sperm), intact males or other females, before mating all females with intact males to assess pregnancy outcomes. We found an increase in litter size at birth in females previously exposed to vasectomized males that was not evident after mating with seminal vesicle-excised males, although the latter comparison had less power. However, postnatal loss of offspring led to similar litter sizes between groups at weaning. In a second study, we observed that females previously housed with vasectomized males and later mated to intact males maintained more fetuses compared with naive females in late pregnancy. Placental morphology was also altered with a significant decrease in the size of the labyrinthine zone, a sign of increased placental efficiency. These results provide experimental evidence that preconception seminal fluid exposure in the absence of conception can improve later pregnancy outcomes in mice.