title: Altered protein expression profiles in umbilical veins: insights into vascular dysfunctions of the children born after in vitro fertilization.
abstract: Cardiovascular dysfunction and remodeling have been found in some children conceived by in vitro fertilization (IVF). However, the underlying mechanisms remain unclear. In this study, the retrospective investigation showed that the blood pressure of IVF-conceived Chinese children was higher than that of naturally conceived (NC) children at ages 3-13 yr. We analyzed the expression profile of proteins in the umbilical veins of IVF and NC newborns by proteomic techniques. Using iTRAQ (isobaric tags for relative and absolute quantitation), 47 differentially expressed proteins (DEPs) were identified by feature selection in IVF umbilical veins compared with NC. Ingenuity Pathway Analysis, which is used to explore the signaling pathways of DEPs, revealed that these DEPs played important roles in vascular system development and carbon metabolism, implying that these DEPs might be potential candidates for further exploration of the mechanism(s) of vascular dysfunction in IVF children. We found that the serum estradiol (E₂) level in the cord blood of IVF newborns was significantly higher than that of NC newborns. High concentrations of E₂ induced alteration of lumican and vimentin expression in human umbilical vein endothelial cells, which was consistent with the proteomic results. These findings suggested that abnormal expression of proteins in umbilical veins might be related to the cardiovascular dysfunction and remodeling in IVF offspring. In conclusion, our data for the first time reveal the protein expression profile in blood vessels of IVF offspring and provide information for further mechanism study and evaluation of risks of cardiovascular abnormality in IVF children.
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Pan
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Lin
authors.affiliation: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Tian
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Lu-Ting
authors.initials: LT
authors.lastname: Chen
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Miao-E
authors.initials: ME
authors.lastname: Liu
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Yi-Meng
authors.initials: YM
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China huanghefg@hotmail.com.
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China shengjz@zju.edu.cn.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005312:Fetal Blood / Q000737:chemistry; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics / Q000378:metabolism; D000071234:Lumican; D008297:Male; D012189:Retrospective Studies; D012306:Risk; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D014652:Vascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014746:Vimentin / Q000378:metabolism
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; D000071234:Lumican; D014746:Vimentin; D004958:Estradiol; D007632:Keratan Sulfate
keywords: IPA; IVF; cardiovascular; iTRAQ; umbilical veins