DNA synthesis is reduced in selected fetal tissues during prolonged hypoxemia

The effects of 24 h of reduced maternal uterine blood flow (RUBF) on relative DNA synthesis rates in different tissues and on blood glucose and lactate concentrations were studied in fetal sheep. In six sheep, RUBF was induced for 24 h, whereas in another six sheep (controls), uterine blood flow was not reduced. To estimate DNA synthesis rate, [³H]thymidine (1 mCi/kg) was injected intravenously into each fetus 8 h before the end of the 24-h experimental period. Fetal arterial oxygen saturation decreased from 59.1 ± 3.3 to 25.7 ± 5.6% after 1 h of RUBF and remained significantly reduced for the duration of the experiment. Fetal blood lactate concentrations were significantly increased by RUBF from 14.3 ± 6.5 to 57.8 ± 12.4 mg/dl at 1 h and remained elevated, whereas fetal blood glucose concentrations were not affected. A 24-h period of RUBF did not significantly alter fetal body weights, tissue weights, tissue-to-body weight ratios, or tissue DNA content. Over the last 8 h of the 24-h experimental period, RUBF was found to significantly reduce the relative rate of DNA synthesis (as assessed by [³H]thymidine incorporation into DNA) in the lung (104.7 ± 26.6 vs. 17.1 ± 3.1 dpm/μg DNA), quadriceps muscle (92.8 ± 20.7 vs. 14.4 ± 5.3 dpm/μg DNA), and thymus gland (87.5 ± 7.1 vs. 32.9 ± 12.2 dpm/μg DNA). Relative DNA synthesis rates in the fetal liver, kidney, small intestine, cerebral cortex, cerebellum, placenta, thyroid gland, and adrenal gland were not significantly affected by RUBF. In this study, we have shown that DNA synthesis was greatly reduced in selected fetal tissues (lung, quadriceps muscle, and thymus gland) by a 24-h period of RUBF, although it is not known why a reduction was only observed in these tissues.