Male mediated caffeine effects over two generations of rats.

Caffeine exposure of a male rat prior to mating affected his progeny and the progeny of a second generation. The dose chosen, 30 mg/kg per day given orally, was approximately equivalent to a caffeine intake of 10-12 cups of brewed coffee daily. In the first (F1) generation caffeine consumption of the sires for a minimum period of 15 days prior to mating with drug naive females, caused significant fetal growth retardation of both sexes and an increased postnatal mortality of pups between weeks 1 and 2, many of which displayed characteristics of runts. Persistent caffeine effects were also found in a second (F2) generation obtained by back breeding male and female F1 offspring from control and treated groups. The F2 pups of both sexes, from the female breeding line, were born significantly heavier when compared with their control counterparts. In the male breeding line, 33% of the litters conceived were aborted in utero, and among the young F2 pups born runts were again evident. At the conclusion of the breeding for the first generation the testes of the FO sires were studied after they received caffeine for 38 consecutive days. The experimental testes showed a marked degeneration characterized by significant overall size reduction, breakdown of the germinal epithelium, accumulation of cellular debris in the lumen of the seminiferous tubules, and significant reduction in the abundance of mature spermatozoa. On ultrastructural examination there appeared to be genetic damage to the spermatozoa where nucleic cysts and pouches were seen.