Maternal dyslipidemia during early pregnancy and epigenetic ageing of the placenta

Abstract

Disruption of physiological ageing of the placenta is associated with obstetric complications. Altered lipid metabolism is a known trigger of tissue ageing, but the effect of maternal dyslipidemia on placental ageing is not clearly understood. We examined the relationship between maternal dyslipidemia and placental age acceleration (PAA), an epigenetic ageing measure derived from the difference between DNA methylation age and chronological gestational age. We also assessed whether the association varies by maternal pre-pregnancy obesity status and fetal sex. Placental data were obtained as part of the NICHD Fetal Growth Studies that involved participants from four race/ethnic groups. Placental DNA methylation age was estimated using 62 CpGs that have previously been found to have high placental age prediction accuracy. We used multivariable linear regression to test associations between maternal dyslipidemia during early gestation (i.e., high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), total cholesterol (TChol), and triglycerides) and PAA adjusting for fetal sex and socio-demographic factors. Among normal-weight women, low HDLc, compared to high HDLc, was associated with 0.82 (95% CI: 0.00, 1.64) weeks higher PAA. Among women with female neonates, low HDLc, compared to high HDLc, was associated with 1.20 (95% CI: 0.17, 2.24) weeks higher PAA. High TChol was associated with 1.28 (95% CI: 0.12, 2.45) weeks higher PAA among Whites. In all, the study found that maternal dyslipidemia due to low HDLc was associated with accelerated epigenetic ageing of the placenta among mothers with normal pre-pregnancy weight and a female fetus.

Evidence of accelerated epigenetic aging in patients diagnosed with coronary artery disease: Results of the LipidCardio study

“…Similarly previous studies have found either a weak or no association: Horvath et al, who observed no association of HDL-cholesterol levels and intrinsic or extrinsic age acceleration, reported a weak association of triglyceride levels and extrinsic age acceleration (ß=0.004, p=0.04), but not intrinsic age acceleration (both measured based on the Horvath clock) in the WHI cohort (Horvath, Gurven, Levine, Trumble, Kaplan, Allayee, Ritz, Chen, Lu, Rickabaugh, Jamieson, Sun, Li, Chen, Quintana-Murci, et al, 2016). women participating in the Fetal Growth Studies -Singleton cohort (Shrestha et al, 2019). While the above findings are considerable, its comparability to our findings is limited.…”

“…Roetker et al reported a weak negative association (ß=-0.65p=0.04) of HDL cholesterol and Horvath DNAm age acceleration, but not the Hannum age acceleration in the ARIC study (Roetker et al, 2018). Interestingly, a niche clinical study accessing epigenetic age of the placenta in the context of maternal dyslipidemia in early pregnancy by Shrestha et al found evidence of an association of low maternal HDL-cholesterol levels (but not high triglyceride levels) and accelerated aging of the placenta (assessed placental age acceleration by the difference of a 62-CpGs estimate and the gestational age) of normal weight mothers and female offspring in 262 women participating in the Fetal Growth Studies - Singleton cohort (Shrestha et al, 2019). While the above findings are considerable, its comparability to our findings is limited.…”

Sex differences in the associations of placental epigenetic aging with fetal growth

“…In pregnancy, Mayne et al predicted placental epigenetic age with high accuracy using DNA methylation at 62 CpGs and found that placental epigenetic age acceleration (PAA), i.e., the difference between placental DNA methylation age and gestational age at delivery, is associated with early onset preeclampsia [41]. Maternal dyslipidemia in early pregnancy has been associated with accelerated epigenetic aging of the placenta in a sex-dependent manner [42].…”

Nutrients and Mother’s Diet in the Epigenetic Regulation of Placenta

“…La existencia de errores en la impresión de los genes puede ser causados por interrupciones epigenéticas que pueden dar como producto la presencia de diferentes fenotipos y dar paso a entidades nosológicas como la restricción del crecimiento fetal, abortos espontáneos, maduración acelerada de la placenta, nacimientos prematuros e incluso se vincula con la presentación de preeclampsia [14,15,24,27].…”