Altered Protein Expression Profiles in Umbilical Veins: Insights into Vascular Dysfunctions of the Children Born after In Vitro Fertilization1

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.

Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic Regulation

“…The maternal characteristics and delivery data were comparable with the NC group, except levels LDL cholesterol, which is slightly elevated in IVF mothers (3.06 ± 0.73 VS 2.47 ± 0.66, P < 0.01). The serum estradiol concentration from umbilical cord blood vessels in IVF women was signi cantly higher than that in NC women, which is coincidence with our previous results [3]. However, there were no obvious differences in fetal birth weight or male birth rate between the NC and IVF born offspring.…”

“…We previously found that offspring born after IVF have a high blood pressure during age 3-13 years-old [3], so does offspring around 2 years-old recruited in our study (85.12 ± 5.23 VS 82.01 ± 4.85, P < 0.05) (Supplementary Table 1). Therefore, we focused on the endothelium-derived factors, such as endothelial nitric oxide synthase (eNOS), which is classical vasodilation factor, endothelin-1(ET1), one of the critical vasoconstriction factors, and vascular endothelial growth factor (VEGF), which is related with endothelial cell proliferation, angiogenesis, and vascular permeability.…”

“…Disturbed intrauterine environment has been proven to be associated with rapid weight gain in early childhood, a higher risk of having high blood pressure in late childhood, a higher number of skin folds, and elevated fasting serum glucose levels concentrations [4,5]. In our laboratory, we have also previously reported that, at the age of 3-13 years-old, the blood pressure of IVF-conceived Chinese children was higher than that of spontaneously conceived born children [3]. While recent studies have focused on the epidemiological consequences of IVF-conceived offspring, few have explored potential molecular mechanism for such outcomes.…”

“…Since the rst in-vitro fertilization (IVF) pregnancy was reported in 1978 [1], an estimated seven million pregnancies have been achieved worldwide by IVF. Recently, increasing studies have proved that IVFconceived fetuses are exposed to a high-estradiol environment in utero, which is closely correlated with increased risk of low birth weight (LBW) and small-for-gestational-age (SGA) [2,3]. Disturbed intrauterine environment has been proven to be associated with rapid weight gain in early childhood, a higher risk of having high blood pressure in late childhood, a higher number of skin folds, and elevated fasting serum glucose levels concentrations [4,5].…”

The first 50 live births after autologous oocyte vitrification in France

“…The absence of ovarian hyperstimulation in the VAO group may account for the lower incidence of hypertension when comparing to ICSI pregnancies. Furthermore, ovarian hyperstimulation has been reported to adversely affect cardiovascular and metabolic profile of children conceived with assisted reproductive technologies [19][20][21]; this is an interesting aspect to be evaluated in VAO children.…”