Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress

Early life adversity is widely recognized as a key risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex bias in susceptibility, presentation, onset, and severity, although the underlying mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes. To determine whether maternal supplementation of docosahexanoic acid (DHA) exerts an effect on offspring outcome following exposure to early prenatal stress (EPS), dams were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 1.0% preformed DHA/kg feed weight (DHA-enriched) or no additional DHA (denoted as the control diet, CTL). Dams were administered chronic variable stress during the first week of pregnancy (embryonic day, E0.5–7.5), and developmental milestones were assessed at E 12.5. Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to the CTL diet. DHA enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS. Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin-like growth binding factor 1 (IGFBP1), in the placenta of CTL diet males exposed to EPS. DHA enrichment in EPS-exposed animals abrogated the male-specific upregulation of PPARα, HIF3α, and IGFBP1. Taken together, these studies suggest that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.

Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress

Early life adversity is widely recognized as a key risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex-bias in susceptibility, presentation, onset and severity, although the underlying mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes. To determine whether maternal supplementation of docosahexanoic acid (DHA) exerts an effect on offspring outcome following exposure to early prenatal stress (EPS), dams were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 1.0% preformed DHA/kg feed weight (DHA-enriched) or no additional DHA (denoted as the control diet, CTL). Dams were administered chronic variable stress during the first week of pregnancy (Embryonic day, E0.5 – 7.5) and developmental milestones were assessed at E 12.5. Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to the CTL diet. DHA-enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS. Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin like growth binding factor 1 (IGFBP1), in placenta of CTL diet males exposed to EPS. DHA-enrichment in EPS-exposed animals abrogated the male-specific upregulation of PPARα, HIF3α, and IGFBP1. Taken together, these studies suggest that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.

Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress

Early life adversity is widely recognized as a key risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex-bias in susceptibility, presentation, onset and severity, although the underlying mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes. To determine whether maternal supplementation of docosahexanoic acid (DHA) exerts an effect on offspring outcome following exposure to early prenatal stress (EPS), dams were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 1.0% preformed DHA/kg feed weight (DHA-enriched) or no additional DHA (denoted as the control diet, CTL). Dams were administered chronic variable stress during the first week of pregnancy (Embryonic day, E0.5 – 7.5) and developmental milestones were assessed at E 12.5. Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to the CTL diet. DHA-enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS. Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin like growth binding factor 1 (IGFBP1), in placenta of CTL diet males exposed to EPS. DHA-enrichment in EPS-exposed animals abrogated the male-specific upregulation of PPARα, HIF3α, and IGFBP1. Taken together, these studies suggest that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.

137 Dietary Supplementations of Ethanolamine and Serine Enhance Docosahexaenoic Acid Deposition in Eggs of Laying Hens

Enrichment of docosahexaenoic-acid (DHA) into eggs of laying-hens may be limited by the availability phospholipids as a deposition sink. The present study was to determine if dietary supplementations of phospholipid-component molecules or synthesis-enhancers: choline, serine, and ethanolamine could elevate phospholipid and DHA enrichment in the eggs and tissues of hens. A total of 50-White-Leghorn-Shavers (42-wk old) were individually caged and divided into 5 groups (n = 10/group). The 5 groups of hens were fed the following diets for 3 wk: Diet-1 = a corn soybean-meal basal-diet, Diet-2 = Diet-1 + 4%-microalgae (Aurantiochytrium, Heliae, Gibert, AZ, 1.81 g-DHA/kg) + choline-chloride (26.3 g/kg diet, 60% purity, DSM-Co., Basel, Switzerland), Diet-3 = Diet-2 + 1.41% of L-serine (100% purity, Ajinomoto-Co., Inc., Kawasaki, Japan), Diet-4 = Diet-2 + 100 mg of ethanolamine/kg (99% purity, Sigma-Aldirch-Co., St Loius, MO), and Diet-5 = Diet-3 + 100 mg of ethanolamine/kg. At the end of study, eggs, liver, ovary, and adipose samples were collected from 6 hens/group for biochemical analysis. Data were analyzed by one-way ANOVA. Compared with Diet-1, Diet-2 enhanced (P < 0.05) DHA concentrations in egg yolk and liver by 213 mg/egg and 2.98 mg/g tissue, respectively, but decreased (P < 0.05) total phospholipid-concentrations of yolk and liver by 50%, and hepatic-mRNA levels of elongases-2/5 and desaturases-4/6 by 25–50%. Compared with Diet-2, Diet-5 enhanced (P < 0.05) DHA (by 20%) and phospholipid (by 40%) concentrations in the egg yolk, and upregulated (P < 0.05) lipid-metabolism genes involved in the citicoline (CDP, up-to-3-fold) and CDP-ethanolamine (up-to-2.5-fold) pathways in the liver and ovary-tissue. In comparison, Diets-3 and 4 resulted in only 3–11% higher (P < 0.05) DHA-concentrations in the liver over Diet-2. In conclusion, feeding hens a high DHA and choline diet enriched DHA in the egg yolk and down-regulated lipogenesis-gene-expression in the tissues. Supplementing the diet with extra-serine and ethanolamine further-enhanced the DHA enrichment in the egg yolk and restored the high DHA-mediated changes in the gene-expression. (Supported in part by DOE-MAGIC-grant DE-EE0007091, USDA-grant 2019-69012-29905, and Cornell-University-Hatch-grants NYC-127419/127302).

Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress

Background: Early life adversity is a risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex-bias in susceptibility, presentation, onset and severity, although mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes. Methods: To determine whether maternal docosahexanoic acid (DHA) supplementation effects offspring outcome following exposure to early prenatal stress (EPS), dams were fed nutritionally complete semi-purified diets that either contained adequate essential omega-6 (n-6) and omega-3 (n-3) fatty acids from corn and soy oils (control diet, CTL) or an experimental diet that was nutritionally-equivalent to the CTL diet, but contained 1% by weight DHA, a long-chain omega-3 fatty acid (22:6n-3). Dams were administered chronic variable stress during the first week of pregnancy (Embryonic day, E0.5 – 7.5). Developmental milestones were assessed at E 12.5. Results: Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to CTL diet. DHA-enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS. Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin like growth binding factor 1 (IGFBP1), in placenta of CTL diet males exposed to EPS. DHA-enrichment in EPS-exposed animals abrogated male-specific upregulation of PPARα, HIF3α, and IGFBP1. Conclusions: This suggests that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.

Mechanism study on the enhanced DHA synthesis in the mutant Thraustochytriidae sp. through comparative transcriptomic analysis

Background: Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid for the human retina, skin, and cerebral cortex. Marine eukaryote Thraustochytriidae sp. was considered as a promising source for the n -3 LC-PUFAs production. However, the mechanism how the LC-PUFAs was synthesized in Thraustochytriidae sp. still remained unclarified. To explore the vital genes responsible for the DHA enrichment, the functional transcriptomic annotation was compared between the wild type and preeminent mutant of Thraustochytriidae sp. X2. Results: After the UV irradiation (50 W, 30 s), the mutant X2 showed enhanced lipid (78.88 % more) and DHA (23.77 % more) production compared with the wild type. Instead of EPA, 9.07 % of DPA was observed in the mutant X2. The comparative transcriptomic analysis showed that in both wild type and mutant strain, FAS was incomplete and lacked key desaturases, but genes related to the PKS pathway were observed. It was oberved that mRNA expression levels of CoA-transferase (CoAT) , acyltransferase (AT), enoyl reductase (ER) , dehydratase (DH) and methyltransferase (MT) down-regulated in wild type but up-regulated in mutant X2, corresponding to the increased intercellular DHA accumulation. Conclusion: These findings indicated the potential genes that can be exploited for high DHA yields in Thraustochytriidae sp..

Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC®

AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of 13C-labeled DHA after oral intake of a single dose of 13C-AceDoPC®, in comparison with 13C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the 13C enrichment of DHA-containing lipids. 13C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, 13C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the 13C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion.