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

Autor: Gary K. Heinemann, Hong Liu, Joshua D. Rabinowitz, Vicki L. Clifton, Damien S. Hunter, Amy L. Wooldridge, Rebecca A. Simmons, Karen L. Kind, Yu-Chin Lien, Kathryn L. Gatford, Julie A. Owens, Robert J Bischof, Lynne C. Giles, Wenyun Lu
Přispěvatelé: Wooldridge, Amy L, Bischof, Robert J, Liu, Hong, Heinemann, Gary K, Hunter, Damien S, Giles, Lynne C, Simmons, Rebecca A, Lien, Yu-Chin, Lu, Wenyun, Rabinowitz, Joshua D, Kind, Karen L, Owens, Julie A, Clifton, Vicki L, Gatford, Kathryn L
Rok vydání: 2018
Předmět:
0301 basic medicine
Physiology
Placenta
Intrauterine growth restriction
mast cells
Dermatitis
Immunoglobulin E
Allergic sensitization
Methionine
0302 clinical medicine
Pregnancy
Mast Cells
Skin
Fetal Growth Retardation
Pyroglyphidae
Gestational age
Cobalt
animal models
medicine.anatomical_structure
In utero
Prenatal Exposure Delayed Effects
Female
Research Article
medicine.medical_specialty
intrauterine growth restriction
Ovalbumin
Gestational Age
Biology
folic acid
03 medical and health sciences
Folic Acid
Physiology (medical)
Internal medicine
Hypersensitivity
medicine
Animals
Sheep
Domestic

House dust mite
DNA Methylation
medicine.disease
biology.organism_classification
methyl donors
Disease Models
Animal

030104 developmental biology
Endocrinology
Dietary Supplements
biology.protein
fetal growth
Sulfur
030215 immunology
Zdroj: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 314:R22-R33
ISSN: 1522-1490
0363-6119
Popis: 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.
Databáze: OpenAIRE