Consequences of supplying methyl donors during pregnancy on the methylome of the offspring from lactating and non-lactating dairy cattle

The aim of this study was to evaluate the potential effects of methyl donor supplementation of pregnant animals in the presence or absence of a concomitant lactation on the methylome of the offspring. Twenty Holstein cows, 10 nulliparous (non-lactating while pregnant) and 10 multiparous (lactating while pregnant) were blocked by parity and randomly assigned to an i.m. weekly injections of a placebo (CTRL) or a solution containing methyl donors (MET). After calving, 5 calves randomly selected from each treatment (two born to non-lactating and three to lactating dams) were blood-sampled to determine their full methylome. There were more than 2,000 CpG differentially methylated between calves born to CTRL and those born to MET, and also between calves born to lactating and non-lactating dams. Most of the differences affected genes involved in immune function, cell growth regulation and differentiation, kinase activity, and ion channeling. We conclude that the coexistence of pregnancy and lactation affects the methylome of the offspring, and that supplementation of methyl donors early in gestation has also consequences on the methylome.

本研究旨在评估妊娠动物补充甲基供体（methyl donor），在伴随泌乳或不伴随泌乳的情况下，对子代甲基化组（methylome）的潜在影响。选取20头荷斯坦奶牛，其中初产（妊娠时非泌乳）10头、经产（妊娠时泌乳）10头，按胎次进行区组设计后随机分为两组，分别每周接受肌肉注射（i.m.）安慰剂（CTRL组）或含甲基供体的溶液（MET组）。产犊后，从每个处理组中随机选取5头犊牛（其中2头来自非泌乳妊娠母牛，3头来自泌乳妊娠母牛）采集血液样本，以测定其全基因组甲基化组。CTRL组与MET组犊牛之间、泌乳妊娠母牛与非泌乳妊娠母牛所产犊牛之间，均存在超过2000个差异甲基化CpG位点。绝大多数差异甲基化位点所影响的基因，涉及免疫功能、细胞生长调控与分化、激酶活性以及离子通道功能。本研究得出结论：妊娠与泌乳的共存会对子代甲基化组产生影响，且妊娠早期补充甲基供体同样会对子代甲基化组造成影响。