Decreased Phospholipid Remodelling May Increase DHA Bioavailability in Maternal Blood During Pregnancy
Authors: Chalil Daniel , Chalil Alan , Stark Ken D 
Published: November 2023

BackgroundDocosahexaenoic acid (DHA) increases in maternal blood during pregnancy. While increases in DHA synthesis during pregnancy have been documented, preliminary lipidomic analyses show that plasma palmitoyldocosahexaenoyl phosphatidylcholine (16:0/DHA‐PC) is responsible for most of this increase.ObjectiveTo examine the mRNA expression of genes involved in Lands' fatty acyl remodeling cycle, PC synthesis, and lipoprotein synthesis to determine mechanisms responsible for increased maternal mobilization of 16:0/DHA‐PC into plasma during pregnancy.MethodsThe effect of pregnancy was examined in Sprague Dawley rats. Time points included a non‐pregnant baseline, day 15 and day 20 of pregnancy, and day‐7 postpartum (n=6 for each group). Rats were sacrificed by exsanguination following anesthesia, after an overnight fast. Tissues were collected, flash frozen in liquid nitrogen and stored in −80ºC. The mRNA was extracted from liver samples and cDNA was prepared. RT‐qPCR was performed using SYBR Green. For Lands' cycle, LPCAT 1–4, and PLA2G IVa, V, VI, X, XV, XVI, and DHA specific ACSL 3 and 6 were examined. For PC synthesis, GPAT 1,3,4, and AGPAT 1,2,4 and 8 were examined. Lipoprotein synthesis was examined by looking at mRNA expression of assembly proteins, ARFRP1, PPARP α, SREBF1, ABCA1, MTTP, and PLTP and apolipoproteins A1, A2, A4, A5, B, and E. Data is expressed relative to 18S as a control, with one‐way ANOVA coupled with posthoc testing to indicate significance.ResultsGenes involved in the Lands' cycle demonstrated the most change with pregnancy. PLA2GXV mRNA expression at day 20 of pregnancy was reduced by 56% as compared with baseline (p<0.05). At day‐7 post‐partum PLA2GXV increased by 401% compared with day 20 (p<0.05). PLA2GV and GXVI displayed similar but not as dramatic mRNA expression patterns, with only the PLA2 GXVI change being significant. ACSL 3 was upregulated by 98% at day 15 compared with baseline and maintained that level expression through day 20 (P<0.05). ACSL6 expression was 93% lower at the end of pregnancy (day 20) compared with baseline and then returned to baseline levels postpartum (P<0.05). For PC synthesis, AGPAT2 expression was reduced by 52% as compared with baseline (p<0.05) and then increased by 218% at day‐7 postpartum compared with day 20. For lipoprotein synthesis, ApoA1 expression increased during pregnancy with a slight decrease postpartum, and ARFRP1 decreased during pregnancy with slight increase postpartum. PPARPα and MTTP were increased at postpartum (P<0.05). No other mRNA expression changes were observed.ConclusionsThe decreased expression of PLA2GXV and AGPAT2 suggest that remodeling of PC is decreased during pregnancy which may cause increased 16:0/DHA‐PC in maternal plasma during pregnancy. There is prior evidence that PC synthesized from phosphatidylethanolamine undergoes remodeling that decreases DHA content under normal physiological conditions. This decreased remodeling may be an appropriate adaptive mechanism during pregnancy to mobilize DHA to meet fetal demand.Support or Funding InformationThis work was supported by a Natural Sciences and Engineering Research Council (NSERC) Discovery grant (327149, to K.D.S), and an NSERC master's scholarship to A.C. K.D.S. is also supported by a Canada Research Chair in Nutritional Lipidomics.