Human luteinized granulosa cells secrete apoB100-containing lipoproteins |
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Authors: | Thomas Gautier Steffi Becker Véronique Drouineaud Franck Ménétrier Paul Sagot Jerzy-Roch Nofer S?ren von Otte Laurent Lagrost David Masson Uwe J F Tietge |
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Institution: | 1. INSERM UMR866 Lipides, Nutrition, Cancer, Faculté de Médecine, Dijon, France;2. Klinik fuer Frauenheilkunde und Geburtshilfe, Universitaetsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;4. Laboratoire de Biologie de la Reproduction, Centre Hospitalier Universitaire de Dijon, Dijon, France;7. Service de Microscopie Electronique, IFR Santé-STIC, Dijon, France;11. Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, Münster, Germany;8. Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands |
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Abstract: | Thus far, liver, intestine, heart, and placenta have been shown to secrete apolipoprotein (apo)B-containing lipoproteins. In the present study, we first investigated lipoproteins in human follicular fluid (FF), surrounding developing oocytes within the ovary, as well as in corresponding plasma samples (n = 12). HDL cholesterol within FF correlated well with plasma HDL cholesterol (r = 0.80, P < 0.01), whereas VLDL cholesterol did not, indicating that VLDL in FF might originate directly from the granulosa cells producing FF. Primary human granulosa cells expressed apoB, microsomal triglyceride transfer protein, and apoE, but not the apoB-editing enzyme apobec-1. Using 3H-leucine, we show that granulosa cells secrete apoB100-containing lipoproteins and that secretion can be stimulated by adding oleate to the medium (+83%). With electron microscopy, apoB-containing lipoproteins within the secretory pathway of human granulosa cells were directly visualized. Finally, we found a positive relationship between apoB levels in FF and improved fertility parameters in a population of 27 women undergoing in vitro fertilization. This study demonstrates that human granulosa cells assemble and secrete apoB100-containing lipoproteins, thereby identifying a novel cell type equipped with these properties. These results might have important implications for female infertility phenotypes as well as for the development of drugs targeting the VLDL production pathway. |
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Keywords: | triglycerides cholesterol VLDL infertility follicular fluid MTP metabolism |
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