title: Human luteinized granulosa cells secrete apoB100-containing lipoproteins.
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 (3)H-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.
authors.affiliation: Faculté de Médecine, INSERM UMR866 Lipides, Nutrition, Cancer, Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.forename: Steffi
authors.initials: S
authors.lastname: Becker
authors.forename: Véronique
authors.initials: V
authors.lastname: Drouineaud
authors.forename: Franck
authors.initials: F
authors.lastname: Ménétrier
authors.forename: Paul
authors.initials: P
authors.lastname: Sagot
authors.forename: Jerzy-Roch
authors.initials: JR
authors.lastname: Nofer
authors.forename: Sören
authors.initials: S
authors.lastname: von Otte
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: David
authors.initials: D
authors.lastname: Masson
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
mesh_terms: D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000737:chemistry; D005260:Female; D005298:Fertility; D015571:Follicular Fluid / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D056945:Hep G2 Cells; D006801:Humans; D034461:Luteinization; D008854:Microscopy, Electron; D019301:Oleic Acid / Q000494:pharmacology
chemical_list: D053299:Apolipoprotein B-100; D002352:Carrier Proteins; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; C106092:microsomal triglyceride transfer protein; D019301:Oleic Acid
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