Impaired reproduction of histamine deficient (histidine-decarboxylase knockout) mice is caused predominantly by a decreased male mating behavior.

PROBLEM: Histamine induces a Th2 shift. As successful allopregnancy is characterized by a peripheral Th2 dominance, we investigated the role of histamine in reproduction. METHOD OF STUDY: HDC knockout (HDC-/-) or wild-type (HDC+/+) mice kept on histamine-deficient or normal diet were mated. Appearance of vaginal plugs indicated day 0.5 of pregnancy. On day 10.5 uteri were inspected. Splenic IFN-gamma production and cytotoxic activity were determined.
RESULTS: In HDC+/+ or HDC-/- females on normal diet, plugs appeared between 3 and 6 days. In 80% of the (HDC-/-)/(HDC-/-) matings on histamine-deficient diet, no vaginal plugs were observed for more than 1 month. After replacing males with the wild type, plugs appeared within 3 days. In HDC-/- mice, litter size was lower than in HDC+/+ animals. Cytotoxicity and IFN-gamma production were significantly increased in non-pregnant histamine-deficient mice, but not in pregnant mice.
CONCLUSION: Histamine affects male mating behavior, but is not indispensable for successful pregnancy.