Does late pregnancy methyl donor supplementation reverse effects of placental restriction on immune function in sheep? — ASN Events
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  3. Does late pregnancy methyl donor supplementation reverse effects of placental restriction on immune function in sheep?

Does late pregnancy methyl donor supplementation reverse effects of placental restriction on immune function in sheep? (#185)

Amy L Wooldridge 1 2 , Rob J Bischof 3 , Els N Meeusen 3 , Hong Liu 1 2 , Gary K Heinemann 1 2 , Damien S Hunter 1 2 4 , Karen L Kind 1 4 , Julie A Owens 1 2 , Vicki L Clifton 1 2 , Kathy L Gatford 1 2
  1. Robinson Institute, Adelaide, SA, Australia
  2. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia
  3. Biotechnology Research Laboratories, Department of Physiology, Monash University, Clayton, VIC, Australia
  4. School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy, SA, Australia

Background: Methyl supplementation during pregnancy increases methyl donors available to the fetus, reducing the risk of neonates developing neural tube defects1. However, epidemiological evidence in humans, and from one study in mice, suggests methyl donor supplements in late pregnancy increase the risk of allergy in progeny2,3. Conversely, fetal growth restriction, which reduces methyl donor supplies to the fetus4, decreases allergy incidence later in life, and we have shown that placental-restriction of fetal growth (PR) decreases allergic responses in sheep. We hypothesised that maternal methyl supplementation in late pregnancy would normalise allergic responses in adolescent PR sheep.

Methods: Outcomes were measured in 47 control (CON) lambs, 28 PR lambs and 25 PR lambs whose mothers were fed methyl donors (PR+METHYL; 2 g rumen-protected methionine, 300 mg, 1.2 g S, 0.7 mg Co/day) from d120 of pregnancy until term delivery. We measured circulating immune cell populations, antibody response to Clostridial vaccination and antibody and skin wheal responses to immunological sensitisation with house dust mite (HDM) and ovalbumin (OVA).

Results: Birth weight was higher in CON singletons (6.1 ± 0.4 kg) than in PR (4.7 ± 0.2 kg, P=0.012) or PR+METHYL singletons (4.0 ± 0.3 kg, P<0.001). Treatment did not affect circulating immune cell populations, antibody responses to Clostridial vaccine, or OVA IgE responses. Overall, HDM IgE responses were greater in PR (P=0.008) and tended to be greater in PR+METHYL sheep (P=0.070) compared to CON sheep. Fewer PR than CON sheep had positive skin wheal responses to OVA in singletons (P=0.006), but not overall (P>0.1). Proportions of positive skin wheal responders to OVA were similar within CON and PR+METHYL groups in singletons and overall. Treatment did not affect the proportions of animals with positive skin wheal responses to HDM.

Conclusions: Decreased skin responses to allergens in PR sheep, despite greater IgE responses, suggest PR acts downstream of IgE-allergen interactions, possibly via reduced mast cell function. Methyl supplementation in late pregnancy partially reverses this phenotype, suggesting epigenetic mechanisms are involved.

  1. Medical Research Council Vitamin Study Research Group (1991) Lancet 338, 131-7.
  2. Hollingsworth JW, Maruoka S, et al. (2008) The Journal of Clinical Investigation 118 (10), 3462-9.
  3. Whitrow MJ, Moore VM, Rumbold AR, Davies MJ (2009) American Journal of Epidemiology 170 (12), 1486-93.
  4. MacLennan NK, James SJ, Melnyk S, Piroozi A, Jernigan S, Hsu JL, Janke SM, Pham TD, Lane RH (2004) Physiological Genomics 19, 43-50.
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