Caffeine-mediated effects on reproductive health over two generations in rats.

The present study was designed to investigate the mechanism(s) underlying previously observed birth weight differences found in the first litter of the second (F2) generation bred from caffeine-exposed F1 females. The effect of exposure to caffeine in utero on subsequent sexual receptivity, fertility, gestation length, parturition, nesting activity, maternal behaviour, and reproductive senescence in the F1 mothers, and the viability of the F2 offspring was investigated. This information was collected by breeding control or caffeine exposed females for 8 consecutive litters. It was demonstrated that exposure to caffeine did not affect the sexual receptivity, fertility, gestation length, or maternal behaviour of the F1 females, but parturition was prolonged and the viability of the F2 generation was seriously jeopardized. Many F2 pups were born significantly larger than their control counterparts and a significant proportion of litters (after the first two litters) were wholly stillborn. It was concluded that a changed genetic program, mediated via the F2 fetus, delayed the normal progression of parturition. This, in turn, compromised the F1 mothers and caused increased mortality of their offspring. The severity of the outcome was dose dependent.