Late-gestation maternal dietary methyl donor and cofactor supplementation in sheep partially reverses protection against allergic sensitization by IUGR

Abstract

Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON; n = 49), from PR pregnancies without intervention (PR; n = 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR + Methyl; n = 25). Both PR and PR + Methyl progeny were smaller than CON; supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA; P < 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR + Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR + Methyl than in PR or CON (each P < 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.

Predictive blood biomarkers of sheep pregnancy and litter size

“…Methionine is an essential amino acid that plays an important role in general animal performance 53 , as well as the growth and development of lambs in early life 54 . Methionine is also a methyl group supplier for epigenetic alteration of DNA, especially in late gestation 55 . Indeed, Sinclair and associates 56 reported widespread epigenetic alterations in progeny, mostly male lambs, resulting from restricted supply of dietary methionine to the pregnant dam.…”

Predictive Blood Biomarkers of Sheep Pregnancy and Litter Size

“…Methionine is an essential amino acid that plays an important role in general animal performance (El-Tahawy and Ismaeil, 2013), as well as the growth and development of lambs in early life (Wang et al, 2018). Methionine is also a methyl group supplier for epigenetic alteration of DNA, especially in late gestation (Wooldridge et al, 2018). Indeed, Sinclair and associates (2007) reported widespread epigenetic alterations in progeny, mostly male lambs, resulting from restricted supply of dietary methionine to the pregnant dam.…”

“…In addition, ewe health and feed related costs would be reduced by adjusting feed based on pregnancy requirements and preventing blind feeding of all animals with the same ration. Moreover, epigenetics and nutrigenomics studies(Sinclair et al, 2007;Wooldridge et al, 2018) have proven that adjusting maternal feed based on pregnancy requirements programs the progeny to be healthier and physiologically more sound than the average lamb.…”

Effect of Folic Acid Intake on Infant and Child Allergic Diseases: Systematic Review and Meta-Analysis

“…In our present meta-analysis, we found that only folic acid supplementation after first trimester group had statistically remarkable relevance for respiratory allergic diseases risk. Wooldridge et al ( 30 ) found that supplementation with methyl donors in the third trimester of pregnancy may increase the risk of allergy. All of the results suggested that methylation in early pregnancy may be useful but in the third trimester there may not be benefit and may be harmful.…”