title: Obesity occurring in apolipoprotein E-knockout mice has mild effects on fertility.
abstract: The Apolipoprotein (Apo) family is implicated in lipid metabolism. There are five types of Apo: Apoa, Apob, Apoc, Apod, and Apoe. Apoe has been demonstrated to play a central role in lipoprotein metabolism and to be essential for efficient receptor-mediated plasma clearance of chylomicron remnants and VLDL remnant particles by the liver. Apoe-deficient (Apoe(-/-)) mice develop atherosclerotic plaques spontaneously, followed by obesity. In this study, we investigated whether lipid deposition caused by Apoe knockout affects reproduction in female mice. The results demonstrated that Apoe(-/-) mice were severely hypercholesterolemic, with their cholesterol metabolism disordered, and lipid accumulating in the ovaries causing the ovaries to be heavier compared with the WT counterparts. In addition, estrogen and progesterone decreased significantly at D 100. Quantitative PCR analysis demonstrated that at D 100 the expression of cytochromeP450 aromatase (Cyp19a1), 3β-hydroxysteroid dehydrogenase (Hsd3b), mechanistic target of rapamycin (Mtor), and nuclear factor-κB (Nfkb) decreased significantly, while that of BCL2-associated agonist of cell death (Bad) and tuberous sclerosis complex 2 (Tsc2) increased significantly in the Apoe(-/-) mice. However, there was no difference in the fertility rates of the Apoe(-/-) and WT mice; that is, obesity induced by Apoe knockout has no significant effect on reproduction. However, the deletion of Apoe increased the number of ovarian follicles and the ratio of ovarian follicle atresia and apoptosis. We believe that this work will augment our understanding of the role of Apoe in reproduction.
authors.affiliation: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Renji hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200135, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Dai
authors.forename: Dong
authors.initials: D
authors.lastname: Cheng
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Meng
authors.forename: Fumiao
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Han
authors.forename: Jianwei
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Guiwen
authors.initials: G
authors.lastname: Yang
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D001141:Aromatase / Q000235:genetics; D005260:Female; D005298:Fertility / Q000502:physiology*; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology* / Q000503:physiopathology*; D006080:Ovarian Follicle / Q000254:growth & development; D010053:Ovary / Q000737:chemistry; D011247:Pregnancy
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D019870:1-Phosphatidylinositol 4-Kinase