Heat stress reduces cow milk yield and results in a significant economic loss for the dairy industry. During lactation, heat stress lowers milk production by 25 to 40% with half of the decrease in milk synthesis resulting from the reduced feed intake. In vitro studies indicate that primary bovine mammary epithelial cells display greater rates of programmed cell death when exposed to high ambient temperatures, which may lead to a decrease in the total number of mammary epithelial cells in the mammary gland, partially explaining the lower milk production of lactating cows under heat stress. The function of mammary cells is also altered by heat stress. In response to heat stress, mammary cells display higher gene expression of heat shock proteins, indicating a need for cytoprotection from protein aggregation and degradation. Further, heat stress results in increased gene expression without altering protein expression of mammary epithelial cell junction proteins, and does not substantially influence the integrity of mammary epithelium. These data suggest that the mammary gland strives to maintain cell-to-cell junction integrity by synthesizing more proteins to compensate for protein losses induced by heat stress. During the dry period, heat stress negatively affects mammary gland development by reducing mammary cell proliferation before parturition, resulting in a dramatic decrease in milk production in the subsequent lactation. In addition to mammary growth, the mammary gland of the heat-stressed dry cow has reduced protein expression of autophagic proteins in the early dry period, suggesting heat stress influences mammary involution. Emerging evidence also indicates that heifers born to cows that experience late-gestation heat stress have lower milk yield during their first lactation, implying that the maternal environment may alter mammary gland development of the offspring. It is not clear if this is due to a direct epigenetic modification of prenatal mammary gland development by maternal heat stress. More research is needed to elucidate the effect of heat stress on mammary gland development and function.

The present review focuses on methyl donor metabolism and nutrition in the periparturient and lactating dairy cow. Methyl donors are involved in one-carbon metabolism, which includes the folate and Met cycles. These cycles work in unison to support lipid, nucleotide, and protein synthesis, as well as methylation reactions and the maintenance of redox status. A key feature of one-carbon metabolism is the multi-step conversion of tetrahydrofolate to 5-methyltetrahyrofolate. Homocysteine and 5-methyltetrahyrofolate are utilized by vitamin B12-dependent Met synthase to couple the folate and Met cycles and generate Met. Methionine may also be remethylated from choline-derived betaine under the action of betaine hydroxymethyltransferase. Regardless, Met is converted within the Met cycle to S-adenosylmethionine, which is universally utilized in methyl-group transfer reactions including the synthesis of phosphatidylcholine. Homocysteine may also enter the transsulfuration pathway to generate glutathione or taurine for scavenging of reactive oxygen metabolites. In the transition cow, a high demand exists for compounds with a labile methyl group. Limited methyl group supply may contribute to inadequate hepatic phosphatidylcholine synthesis and hepatic triglyceride export, systemic oxidative stress, and compromised milk production. To minimize the perils associated with methyl donor deficiency, the peripartum cow relies on de novo methylneogenesis from tetrahydrofolate. In addition, dietary supplementation of rumen-protected folic acid, vitamin B12, Met, choline, and betaine are potential nutritional approaches to target one-carbon pools and improve methyl donor balance in transition cows. Such strategies have merit considering research demonstrating their ability to improve milk production efficiency, milk protein synthesis, hepatic health, and immune response. This review aims to summarize the current understanding of folic acid, vitamin B12, Met, choline, and betaine utilization in the dairy cow. Methyl donor co-supplementation, fatty acid feeding strategies that may optimize methyl donor supplementation efficacy, and potential epigenetic mechanisms are also considered.

Prenatal heat stress during late gestation exerts long-term effects on growth and productivity of the dairy calf. Further, direct exposure to heat stress during the preweaning period impairs calf thermoregulation and performance. We examined the effects of heat stress abatement during the prenatal period, postnatal period, or both on calf performance. We hypothesized that calves exposed to pre- and postnatal heat stress abatement would perform most optimally in terms of thermoregulation, growth, and health responses when compared with calves that are heat-stressed at any time in the pre- or postnatal periods. Holstein calves born to heat-stressed (HT) or cooled (CL) dams during late gestation (44 ± 5 d; prenatal HT or CL) were exposed to heat stress or cooling postnatally for 56 d (postnatal HT or CL), resulting in 4 treatments: HT-HT, HT-CL, CL-HT, and CL-CL; n = 12/treatment. Calves were administered 4 L of pooled colostrum and after 2 d of age allotted 10 L/d milk replacer and up to 3 kg/d concentrate in automatic feeder group pens (n = 6/pen). Postnatal cooling was achieved by 2 fans (average wind speed 2 m/s). Thermoregulatory responses (respiration rate and heart rate; rectal, body, and skin temperature), feed intake, growth parameters including average daily gain and medication events were recorded, and blood samples were collected weekly. Thermoregulatory responses were lower in postnatal CL calves compared with postnatal HT. In the afternoon, HT-HT calves had the highest respiration rate and rectal temperature, HT-CL calves had the lowest respiration rate, and CL-HT calves had the lowest heart rate compared with the other treatment groups. Prenatal CL calves weighed more at birth and weaning with a tendency for greater average daily gain compared with prenatal HT calves, whereas postnatal CL calves had increased milk replacer and concentrate intake and a tendency for reduced fever, infection, and total medication events relative to postnatal HT. Prenatal HT calves were esophageal tube fed more often than prenatal CL. Blood hematocrit and 24-h serum IgG concentration were greater in prenatal CL calves relative to prenatal HT. Prenatal heat stress abatement improves weight gain, hematocrit, and immunoglobulin transfer, whereas postnatal heat stress abatement modulates thermoregulatory responses, feed intake, and calf health. This study is the first to characterize the combined effects of pre- and postnatal heat stress or active cooling on the dairy calf.

Preliminary studies suggest that maternal heat stress (HS) during late gestation exerts carryover effects on a calf's insulin response after weaning, but a comprehensive evaluation of how maternal HS affects calf intake, growth, and metabolic response from birth to weaning is lacking. Our objective was to evaluate the effects of maternal HS during the dry period on dry matter intake, growth, and metabolism from birth to weaning. After birth, 20 heifers born to either HS (n=10) or cooled (CL, n=10) dry cows were immediately separated from their dams and fed 3.8 L of colostrum from a common pool within 4h of birth. All heifers were managed identically and weaned at 49 d of age (DOA). Calf starter intake was recorded daily, and body weight was assessed at birth and every 2 wk from birth to 56 DOA. Blood samples were collected twice a week until 56 DOA to assess hematocrit and concentrations of insulin and metabolites. To evaluate metabolic responses to maternal HS, a glucose tolerance test, insulin, and epinephrine challenge were performed on 3 consecutive days for all heifers at 8, 29, and 57 DOA. Maternal HS during the dry period did not affect heifer birth weight. Compared with HS, CL calves consumed more starter (0.53 vs. 0.34kg/d) from birth to 56 DOA and were heavier (71.7 vs. 61.4kg) at 56 DOA. Relative to HS calves, CL calves tended to have higher hematocrit (27.4 vs. 24.7%). No differences were found between treatments in plasma concentrations of insulin and glucose, but HS calves had higher nonesterified fatty acids and β-hydroxybutyrate concentrations after 32 DOA. Compared with CL, HS calves had a faster glucose clearance after a glucose tolerance test and a slower insulin clearance after an insulin challenge. In conclusion, maternal HS during late gestation reduces calf starter intake and growth, alters blood metabolite profile, and increases noninsulin-dependent glucose uptake.

Heat stress during late gestation in cattle negatively impacts the performance of the dam and its calf. This brief exposure to an adverse environment before parturition impacts the physiological responses, tissue development, metabolism and immune function of the dam and her offspring, thereby limiting their productivity. During the dry period of a dairy cow, heat stress blunts mammary involution by attenuating mammary apoptosis and autophagic activity, and reduces subsequent mammary cell proliferation, leading to impaired milk production in the next lactation. Dairy cows in early lactation that experience prepartum heat stress display reduced adipose tissue mobilization and lower degree of insulin resistance in peripheral tissues. Similar to mammary gland development, placental function is impaired by heat stress as evidenced by reduced secretion of placental hormones (e.g., estrone sulfate) in late gestation cows, which partly explains the reduced fetal growth rate and lighter birth weight of the calves. Compared with dairy calves born to dams that are exposed to evaporative cooling during summer, calves born to non-cooled dry cows maintain lower body weight until 1 yr of age, but display a stronger ability to absorb glucose during metabolic challenges postnatally. Immunity of the calves, both passive and cell-mediated immune function, is also impaired by prenatal heat stress, resulting in increased susceptibility of the calves to diseases in their postnatal life. In fact, dairy heifers born to heat-stressed dry cows without evaporative cooling have a greater chance leaving the herd before puberty compared with heifers born to dry cows provided with evaporative cooling (12.2 vs. 22.7%). Dairy heifers born to late gestation heat-stressed dry cows have lower milk yield at maturity during their first and second lactations. Emerging evidence suggest that late gestation heat stress alters the mammary gland microstructure of the heifers during the first lactation, and exerts epigenetic alterations that might explain, in part their impaired productivity.