Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight

Watkins, Oliver C; Selvam, Preben; Pillai, Reshma Appukuttan; Cracknell-Hazra, Victoria K. B.; Yong, Hannah Ee Juen; Sharma, Neha; Cazenave-Gassiot, Amaury; Bendt, Anne K.; Godfrey, Keith M.; Lewis, Rohan M.; Wenk, Markus R.; Chan, Shiao‐Yng

doi:10.1186/s10020-021-00344-w

Cited by 10 publications

(9 citation statements)

References 82 publications

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“…While the bulk of endogenous 12 C-AA lipids were PEs (32.8%) and PE-Ps (35.4%), for freshly produced 13 C-AA lipids most were TGs (75.1%), with less found in PEs (2.8%), PE-Ps (6.3%) and PIs (5.9%) ( Figure 1 ). This indicates that TGs made up a much greater proportion of newly synthesized AA lipids, while PE, PE-P and PI phospholipids were produced more slowly consistent with previous findings for other fatty acids (Palmitic acid: PA, Oleic acid: OA and Docosahexaenoic acid: DHA) [ 30 , 35 , 36 ].…”

Section: Resultssupporting

confidence: 88%

“…Our previous work suggested that the maternal metabolic environment in utero programs the response of the placenta to in vitro treatments [ 30 , 38 ]. We therefore tested for associations between maternal BMI, fasting glycemia and 2 h glycemia, with the subsequent alterations in 13 C-AA lipids in response to glucose or myo-inositol or combined treatments in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…Placental explants were cultured as previously described [ 30 ]. Briefly, five pieces of villous placental tissue were biopsied from across the placenta then cut into small explants (~3 mm 3 ).…”

Section: Methodsmentioning

confidence: 99%

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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism

et al. 2022

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Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with 13C-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 µM). Newly synthesized 13C-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of 13C-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of 13C-AA-triacylglycerides (TGs) relative to total placental 13C-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four 13C-AA-phospholipids and eleven 13C-AA-TGs, whilst 17 mM glucose increased 13C-AA-PC-40:8 and 13C-AA-LPC. Glucose-induced alterations in all 13C-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 µM myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

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Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism

et al. 2022

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“…Villous placental explants were cultured as previously described [ 79 ]. Briefly, five pieces of villous placental tissue were biopsied from five different sites across the placenta.…”

Section: Methodsmentioning

confidence: 99%

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

Watkins

Yong

Mah

et al. 2022

IJMS

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Pregnancy complications such as maternal hyperglycemia increase perinatal mortality and morbidity, but risks are higher in males than in females. We hypothesized that fetal sex-dependent differences in placental palmitic-acid (PA) and oleic-acid (OA) metabolism influence such risks. Placental explants (n = 22) were incubated with isotope-labeled fatty acids (13C-PA or 13C-OA) for 24 or 48 h and the production of forty-seven 13C-PA lipids and thirty-seven 13C-OA lipids quantified by LCMS. Linear regression was used to investigate associations between maternal glycemia, BMI and fetal sex with 13C lipids, and between 13C lipids and birthweight centile. Placental explants from females showed greater incorporation of 13C-OA and 13C-PA into almost all lipids compared to males. Fetal sex also influenced relationships with maternal glycemia, with many 13C-OA and 13C-PA acylcarnitines, 13C-PA-diacylglycerols and 13C-PA phospholipids positively associated with glycemia in females but not in males. In contrast, several 13C-OA triacylglycerols and 13C-OA phospholipids were negatively associated with glycemia in males but not in females. Birthweight centile in females was positively associated with six 13C-PA and three 13C-OA lipids (mainly acylcarnitines) and was negatively associated with eight 13C-OA lipids, while males showed few associations. Fetal sex thus influences placental lipid metabolism and could be a key modulator of the impact of maternal metabolic health on perinatal outcomes, potentially contributing toward sex-specific adaptions in which females prioritize survival.

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“…Maternal obesity is correlated with higher birth weight and is usually associated with n-3 fatty acid deficiency [92]. In utero n-3 PUFA deficiency programs the fetal brain growth and maturation and reduces neuronal and behavioural plasticity in adulthood [93].…”

Section: Maternal Lipid Transport and Metabolism And Fetal Brain Deve...mentioning

confidence: 99%

Maternal Obesity and Gut Microbiota Are Associated With Fetal Brain Development

Basak¹,

Das²,

Banerjee³

et al. 2022

Preprint

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Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity and a high-fat diet in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed.

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Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight

Cited by 10 publications

References 82 publications

Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism

Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

Maternal Obesity and Gut Microbiota Are Associated With Fetal Brain Development

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