Forskning
February 10, 2012
Role f p53-dependent placental apoptosis in the reproductive and developmental toxicities of caffeine in rodents
J Huang et al, Role f p53-dependent placental apoptosis in the reproductive and developmental toxicities of caffeine in rodents, Clinical and Experimental Pharmacology and Physiology, 2012, Accepted Article.
SUMMARY
To evaluate the role of placental apoptosis in mediating the reproductive and developmental toxicity of caffeine in rodents. Female Kunming mice were treated with caffeine (60, 120 and 240 mg/kg per day) before and during pregnancy. The conception rate, maternal bodyweight gain, placental weight and indices of fetal development, including intrauterine growth retardation rate, were determined on gestational day 18. Female Wistar rats were treated with caffeine (20, 60 and 180 mg/kg per day) from gestational day 11 to gestational day 20. The intrauterine growth retardation rate, maternal plasma angiotensin II and prolactin concentrations, placental pathology, expression of angiotensin AT1 and AT2 receptors and apoptosis related proteins were measured on gestational day 20. In mice, caffeine treatment reduced the total conception rate and delayed conception, and decreased the maternal bodyweight gain, placental weight, fetal bodyweight, and fetal body and tail lengths while intrauterine growth retardation rate increased. In rats, caffeine treatment decreased placental weight and fetal bodyweight, and increased the intrauterine growth retardation rate. Abnormal placental structures and decreased maternal plasma prolactin concentrations were observed following caffeine treatment, which resulted in rennin-angiotensin system activity, including maternal plasma AngII concentration and placental AT1B and AT2 receptors expression, and Bax and p53 expression, while decreases in placental Bcl-2 expression. Caffeine ingestion has detrimental effects on the reproductive system and fetal development in rodents that are associated with chronic activation of the maternal and placental RAS and induction of p53-dependent placental apoptosis.
