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Role of p53‐dependent placental apoptosis in the reproductive and developmental toxicities of caffeine in rodents
Author(s) -
Huang Jing,
Zhou Shu,
Ping Jie,
Pan Xiaoliang,
Liang Gai,
Xu Dan,
Kou Hao,
Bao Chong,
Wang Hui
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05676.x
Subject(s) - endocrinology , medicine , fetus , caffeine , placenta , prolactin , developmental toxicity , biology , angiotensin ii , pregnancy , receptor , hormone , genetics
SummaryThe aim of the present study was 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 developmental, including the rate of intrauterine growth retardation ( IUGR ; i.e. the actual number of fetuses exhibiting IUGR as a percentage of the total number of fetuses), were determined on gestational day ( GD ) 18. Female W istar rats were treated with caffeine (20, 60 and 180 mg/kg per day) from GD 11 to GD 20. The IUGR rate, maternal plasma angiotensin ( A ng) II and prolactin concentrations, placental pathology, expression of angiotensin AT 1 and AT 2 receptors and apoptosis‐related proteins were measured on GD 20. In mice, caffeine treatment dose‐dependently reduced the total conception rate, delayed conception and decreased maternal bodyweight gain, placental weight, fetal bodyweight and fetal body and tail lengths, whereas the IUGR rate was increased. In rats, caffeine treatment dose‐dependently decreased placental weight and fetal bodyweight and increased the IUGR rate. Abnormal placental structures and decreased maternal plasma prolactin concentrations were observed following 180 mg/kg per day caffeine treatment, which resulted in increases in renin–angiotensin system ( RAS ) activity, including maternal plasma Ang II concentrations and placental AT 1B and AT 2 receptor expression, and B ax and p53 expression, but decreases in placental B cl‐2 expression. On the basis of the results of the present study, it appears that 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.