Pituitary adenylate cyclase-activating polypeptide (PACAP) is important for embryo implantation in mice.

Mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) show high mortality during the postnatal period, as well as impaired reproduction in females. This study characterizes the reproductive phenotype in female mice lacking PACAP due to targeted disruption (knockout) of the single copy pacap gene (Adcyap1) to determine the site(s) of action of PACAP in the cascade of reproductive events. PACAP null females showed normal puberty onset, estrous cycles, and seminal plugs when paired with a male of proven fertility. However, significantly fewer PACAP null females (21%) than wild-type females (100%) gave birth following mating. Although a defect was not detected in ovulation, ovarian histology or fertilization of released eggs in PACAP null females, only 13% had implanted embryos 6.5 days after mating. Associated with the decrease in implantation, prolactin and progesterone levels were significantly lower in females lacking PACAP than in wild types on day 6.5 after mating. Our evidence suggests that impaired implantation is the defect responsible for decreased fertility in PACAP null female mice.