Blood flow changes and conceptal development in pregnant rats in response to caffeine

Abstract

Alterations in blood flow to the uterus and its contents during pregnancy have been suggested to account for the teratogenicity and/or embryotoxicity of several agents, including caffeine. Using a radioactive microsphere technique, blood flow to several maternal organs, including ovary, uterus, decidua, and chorioallantoic placenta (CAP), was measured following a single dose of 0 or 120 mg/kg caffeine by gavage to pregnant CD rats on Day 12 of gestation. At 1 or 4 hr after treatment, animals were anesthetized and strontium 85-labeled microspheres (25-μm diam) were infused into the left ventricle. Whole body and tissue radioactivity were determined. Maternal cardiac output (CO) and absolute flow ( f 1; ml/min), relative flow ( f 2; ml/min/g tissue), and flow as %CO ( f 3) to each tissue were calculated. Maternal CO was not altered. All blood flow parameters for ovaries, uterus, and bladder were reduced in treated animals at both time points except for absolute flow ( f 1) to the ovaries at 1 hr. Decidual changes included reduced weight at 1 hr, reduced f 2 at 4 hr, and reduced f 1 and f 3 at both times. However, CAP weight and blood flow were not significantly altered by caffeine treatment. Examination of conceptuses from these litters, and from other animals at 24 hr after treatment or at term did not reveal any significant effect of this dose of caffeine on viability, growth, or physical development. The ratio of embryo to maternal blood caffeine concentrations was approximately 1, indicating free transfer of caffeine to the embryo. Thus, a single dose of caffeine significantly reduced blood flow to the ovary, total uterus, and decidua, while conceptal development appeared normal.