title: Prenatal ethanol exposure induces the osteoarthritis-like phenotype in female adult offspring rats with a post-weaning high-fat diet and its intrauterine programming mechanisms of cholesterol metabolism.
abstract: Osteoarthritis (OA) development is associated with hypercholesterolemia in adults. Our previous study demonstrated that offspring with intrauterine growth retardation (IUGR) due to prenatal ethanol exposure (PEE) had a high risk of developing hypercholesterolemia and metabolic syndrome when fed a post-weaning high-fat diet (HFD). In this study, we examined the changes in articular chondrocytes of IUGR offspring induced by PEE and explored its intrauterine programming mechanisms related to cholesterol metabolism. Using the PEE/IUGR model, serum and tibias from female fetuses and adult female offspring fed a post-weaning HFD were collected and examined for cholesterol metabolism and histology. The results showed that PEE adult offspring manifested significant catch-up growth. Their serum total cholesterol (TCH) and low-density lipoprotein-cholesterol increased and high-density lipoprotein-cholesterol decreased; the osteoarthritis-like phenotype and an increased TCH content were observed in articular cartilage; and the expression of insulin-like growth factor1 (IGF1) and cholesterol efflux pathway, including ATP-binding-cassette transporter A1 and liver X receptor, was reduced. The expression of IGF1 and cholesterol efflux pathway was also lower in the PEE fetuses. This study showed PEE could induce an enhanced susceptibility to HFD-induced OA in adult female IUGR offspring. The underlying mechanism related to cholesterol accumulation in cartilage mediated by intrauterine programming.
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: niqubo@163.com.
authors.forename: Qubo
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: wang-lin-long@163.com.
authors.forename: Linlong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 13437134625@163.com.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. Electronic address: lancersheen@163.com.
authors.forename: Lang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: heart.blue@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 49684567@qq.com.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Université de Lorraine, Ingénierie Moléculaire, Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS, Biopôle, F-54505 Vandœuvre-lès-Nancy, France. Electronic address: jacques.magdalou@univ-lorraine.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Magdalou
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: lbchen@whu.edu.cn.
authors.forename: Liaobin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000071518:Liver X Receptors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010003:Osteoarthritis / Q000139:chemically induced* / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D002791:Cholesterol, Dietary; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D000071518:Liver X Receptors; D020782:Matrix Metalloproteinases; D057093:Orphan Nuclear Receptors; C577834:Abca1 protein, rat; C548904:insulin-like growth factor-1, rat
keywords: Ethanol; Intrauterine growth retardation; Intrauterine programming alteration; Osteoarthritis; Serum cholesterol