Maternal high density lipoproteins affect fetal mass and extra-embryonic fetal tissue sterol metabolism in the mouse.
Previous studies have shown that antibodies to cubulin, a receptor on the yolk sac that binds high density lipoproteins (HDL) and cobalamin, induce fetal abnormalities. Mice with markedly low concentrations of plasma HDL-cholesterol (HDL-C) give birth to healthy pups, however. To establish whether maternal HDL-C has a role in fetal development, sterol metabolism was studied in the fetus and extra-embryonic fetal tissues in wild-type and apolipoprotein A-I-deficient mice (apoAI-/-). Maternal HDL-C content was markedly greater in apoAI+/+ mice prior to pregnancy and at 13 days into gestation. By 17 days into gestation, HDL-C content was similar between both types of mice. Fetuses from apoAI (-/- x -/-) matings were 16;-25% smaller than control mice at 13 and 17 days of gestation and contained less cholesterol. The differences in size and cholesterol content were not due to a lack of cholesterol synthesis or apoA-I in the fetus. In the yolk sac and placenta, sterol synthesis rates were approximately 50% greater in the 13-day-old apoAI-/- mice as compared to the apoAI+/+ mice. Even though synthesis rates were greater, cholesterol concentrations were 22% lower in the yolk sac and similar in the placenta of apoAI-/- mice as compared to tissues of wild-type mice. These data suggest that a difference in maternal HDL-C concentration or composition can affect the size of the fetus and sterol metabolism of the yolk sac and placenta in the mouse.
McConihay
J A
JA
Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Honkomp
A M
AM
Granholm
N A
NA
Woollett
L A
LA
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D020567:Fetal Weight; D005333:Fetus / Q000002:abnormalities*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D013261:Sterols / Q000378:metabolism*
D016632:Apolipoprotein A-I; D017931:DNA Primers; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; D013261:Sterols; C029486:intrinsic factor-cobalamin receptor