Abstract
Maternal dyslipidemia during pregnancy has been associated with suboptimal fetal growth and increased cardiometabolic diseasse risk in offspring. Altered placental function driven by placental gene expression is a hypothesized mechanism underlying these associations. We tested the relationship between maternal plasma lipid concentrations and placental gene expression. Among 64 pregnant women from the NICHD Fetal Growth Studies–Singleton cohort with maternal first trimester plasma lipids we extracted RNA-Seq on placental samples obtained at birth. Placental gene co-expression networks were validated by regulatory network analysis that integrated transcription factors and gene expression, and genome-wide transcriptome analysis. Network analysis detected 24 gene co-expression modules in placenta, of which one module was correlated with total cholesterol (r = 0.27, P-value = 0.03) and LDL-C (r = 0.31, P-value = 0.01). Genes in the module (n = 39 genes) were enriched in inflammatory response pathways. Out of the 39 genes in the module, three known lipid-related genes (MPO, PGLYRP1 and LTF) and MAGEC2 were validated by the regulatory network analysis, and one known lipid-related gene (ALX4) and two germ-cell development-related genes (MAGEC2 and LUZP4) were validated by genome-wide transcriptome analysis. Placental gene expression signatures associated with unfavorable maternal lipid concentrations may be potential pathways underlying later life offspring cardiometabolic traits. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT00912132.
Highlights
Offspring exposed to maternal dyslipidemia during pregnancy may have suboptimal fetal growth, (Mossayebi et al, 2014; Farias et al, 2017), and may be at higher risk of cardiometabolic diseases in later life such as dyslipidemia, atherosclerosis, hypertension, obesity and type 2 diabetes. (Curhan et al, 1996; Pettitt and Jovanovic, 2001; Samaras et al, 2003)
Among the 64 women included in the analysis the mean maternal age and pre-pregnancy BMI were 27.6 (5.8) yeas and 23.3 (3.0) kg/ m2, respectively, and 22% had high total cholesterol, 44% had high LDL-C, 17% had high triglycerides and 16% had low HDL-C at enrollment (Table 1)
LCN2 gene expression in placenta did not differ by total cholesterol status (P-value 0.93) but tended to be upregulated in women with high LDL-C status (P-value 0.085, Supplementary Figure S6)
Summary
Offspring exposed to maternal dyslipidemia during pregnancy may have suboptimal fetal growth, (Mossayebi et al, 2014; Farias et al, 2017), and may be at higher risk of cardiometabolic diseases in later life such as dyslipidemia, atherosclerosis, hypertension, obesity and type 2 diabetes. (Curhan et al, 1996; Pettitt and Jovanovic, 2001; Samaras et al, 2003). Offspring exposed to maternal dyslipidemia during pregnancy may have suboptimal fetal growth, (Mossayebi et al, 2014; Farias et al, 2017), and may be at higher risk of cardiometabolic diseases in later life such as dyslipidemia, atherosclerosis, hypertension, obesity and type 2 diabetes. The concept of fetal programming of cardiometabolic diseases is well documented, (Barker, 1998), the mechanisms are not clearly understood. As the key organ of the maternal-fetal exchange and lipid radicals transfer, the placenta can play a role in this programming. Studies have reported modifications of placental expression of genes related to lipids in obese compared to lean pregnant women (Hirschmugl et al, 2017) and in rabbits with type-1-diabetes. Some studies have highlighted the impact of a maternal high-fat/obesogenic diet on placental transcriptome among rats (Lin et al, 2019) and mice; (King et al, 2013); to our knowledge there has been no study on the impact of maternal lipid concentrations on placental gene expression
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
