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Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)–deficient mice
Helena E. Miettinen, … , Helen Rayburn, Monty Krieger
Helena E. Miettinen, … , Helen Rayburn, Monty Krieger
Published December 1, 2001
Citation Information: J Clin Invest. 2001;108(11):1717-1722. https://doi.org/10.1172/JCI13288.
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Article

Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)–deficient mice

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Abstract

Mammalian female fertility depends on complex interactions between the ovary and the extraovarian environment (e.g., the hypothalamic-hypophyseal ovarian axis). The role of plasma lipoproteins in fertility was examined using HDL-receptor SR-BI knockout (KO) mice. SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes, and are infertile. Fertility was restored when the structure and/or quantity of abnormal HDL was altered by inactivating the apoAI gene or administering the cholesterol-lowering drug probucol. This suggests that abnormal lipoprotein metabolism can cause murine infertility — implying a functional hepatic-ovarian axis — and may contribute to some forms of human female infertility.

Authors

Helena E. Miettinen, Helen Rayburn, Monty Krieger

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Figure 1

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Effects of genetic disruption of the apoA-I gene (a) or probucol treatme...
Effects of genetic disruption of the apoA-I gene (a) or probucol treatment (b and c) on plasma lipoprotein profiles of wild-type and SR-BI KO mice. Plasma lipoproteins were separated by size-exclusion chromatography (Superose 6-FPLC), and total cholesterol was measured for each fraction (expressed as milligrams per deciliter of plasma). Approximate elution positions of VLDL, IDL/LDL, and HDL are indicated as described previously (19). Lipoprotein-cholesterol profiles of (a) wild-type (dashed line, pooled plasma from four mice); SR-BI KO mice (open circles, pooled plasma from seven mice); apoA-I KO mice (open triangles, pooled plasma from three mice); and SR-BI/apoA-I double-KO mice (filled triangles; average of three chromatograms from three mice); (b) wild-type mice fed first with normal chow (open squares, pooled plasma from four mice, same as dashes in a); then with 0.5% probucol-enriched chow for 11 days (filled squares, pooled plasma from four mice); and (c) SR-BI KO mice fed first with normal chow (open circles, pooled plasma from seven mice, same as in a); and then with 0.5% probucol-enriched chow for 25 days (filled circles, pooled plasma from seven mice). The average plasma total cholesterol levels (± SEM) were: wild-type, 103.4 ± 3.8 mg/dl (n = 7); SR-BI KO, 211.5 ± 6.2 mg/dl (n = 13); apoA-I KO, 25 ± 1.2 mg/dl (n = 3); SR-BI/apoA-I KO, 105.3 ± 19.2 mg/dl (n = 3); probucol-fed wild-type, 33.6 ± 3.4 mg/dl (n = 9); probucol-fed SR-BI KO, 107.8 ± 6.3 mg/dl (n = 14). All total cholesterol differences greater than 10 mg/dl were statistically significant (P < 0.05).

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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