Abstract
A fetal hamster increases in mass almost 100-fold in the third trimester of gestation. During this 5.5-day period, the acquisition of over 4 mg of cholesterol is required for normal development. The purpose of the present studies was to determine the potential source(s) of this fetal sterol. Rates of cholesterol synthesis in the whole fetus were measured initially. Synthesis rates in the whole fetus increased linearly from 10 days (approximately 25 nmol sterol/h) through 13.5 days of gestation (approximately 400 nmol sterol/h). During the last 1.5 days of intrauterine development, rates remained constant. Even though the synthesis rates were relatively elevated, as compared to those in an adult, the amount of cholesterol synthesized was about half of that accrued. When synthesis rates in all of the fetal tissues were summed, however, a majority of the sterol in the fetus could now be accounted for. During this same time when the fetus was accumulating 4 mg of cholesterol, the placenta and yolk sac increased in cholesterol content by 2.5 mg, indicating the need for a second source of sterol for fetal tissue development. Two other sources of sterol for these tissues were found to be maternal low density and high density lipoprotein (LDL and HDL, respectively). In fact, more than 0.9 mg of cholesterol was taken up during the third trimester as LDL. To summarize, a majority of cholesterol in the fetus could be accounted for by synthesis in all fetal tissues. Additionally, a significant amount of cholesterol was taken up as maternal-derived LDL and HDL by these same tissues.
Highlights
A fetal hamster increases in mass almost 100fold in the third trimester of gestation
Children, and adults consume their exogenous source of sterol. This cholesterol would correspond to any source of sterol that has been transferred by way of the placenta and yolk sac to the fetus, and could include cholesterol synthesized within these other fetal tissues and/or cholesterol derived from the maternal circulation in the form of lipoproteins
The placenta increases on average 570 g in mass [10] during the course of pregnancy which corresponds to an additional 1140 mg of cholesterol required for tissue growth alone [11].As might be expected in tissues of Abbreviations: LDL, low density lipoprotein; HDL, high density lipoprotein; DPS, digitonin-precipitable sterols; apoB-100, apolipoprotein B-100; TCB, tyramine cellobiose; LDL-C and HDL-C, cholesterol carried in LDL and HDL, respectively; apo.4-I, apolipoprotein A-I; VLDL, very low density lipoprotein; apoE, apolipoprotein E; LRP, LDL receptor-related protein; gp330. glycoprotein 330
Summary
A fetal hamster increases in mass almost 100fold in the third trimester of gestation. Children, and adults consume their exogenous source of sterol In the fetus, this cholesterol would correspond to any source of sterol that has been transferred by way of the placenta and yolk sac to the fetus, and could include cholesterol synthesized within these other fetal tissues and/or cholesterol derived from the maternal circulation in the form of lipoproteins. The newly synthesized cholesterol in these tissues could be used either for membrane formation or be transported across the placenta to the fetus through a not yet defined pathway This sterol would most likely not be used for hormone production as the reproductive steroid hormones appear to be derived preferentially from cholesterol carried in maternal lipoproteins [13, 14]which bind to these fetal tissues and are internalized both in vitro and in vivo [5, 15,16,17]
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