Folic acid supplementation regulates milk production variables, metabolic associated genes and pathways in perinatal Holsteins

Abstract

Perinatal period is the critical time in dairy cattle due to negative energy balance and high milk production stress. Being a key role in biosynthesis and methylation cycle, folic acid is considered essential for lactational and metabolic performance in dairy cattle. Thus, the current study was designed to evaluate the effect of folic acid supplementation on milk production phenotypic traits in periparturient cows. Transcriptomic screening was performed for milk production and metabolism‐associated differentially expressed genes. The 123 cows having similar parity, weight and expected date of calving were randomly selected and divided into three groups; A (n = 41, folic acid 240 mg/500 kg cow/day), B (n = 40, FA 120 mg/500 kg cow/day) and C (Control, n = 42). Folic acid was supplemented for 21 days (14 days pre‐ and seven days post‐calving), and three samples of blood lymphocytes were taken on day seven post‐calving from each folic acid‐treated and control group. In addition, the milk samples for each folic acid‐treated group have been collected at 2nd, 3rd and 4th month of lactation. The increase in average milk yield noticed in group B were significantly (p‐value < .05) higher than C and A. However, the data showed no noteworthy differences for milk fat and milk protein among the three groups. The transcriptomic analysis revealed that folic acid treatment regulated many key metabolic‐related genes (DGAT2, ALOX5, LAP3, GPAT3, GGH, ALDOA, TKT) and pathways (glycolysis, folate biosynthesis, glutathione metabolism, etc.) in periparturient dairy cattle. It was concluded from the above findings that 120 mg/500 kg of folic acid quantity could be considered as a standard during the periparturient period to enhance the milk production performance of dairy cows. The transcriptomic profile revealed several metabolic and milk production‐associated genes which could be a useful addition to the marker selection for the enhancement of metabolism and milk production of periparturient dairy cows.

Overview of Folic Acid Supplementation Alone or in Combination with Vitamin B12 in Dairy Cattle during Periparturient Period

“…The inadequate supply of folic acid may lead to a DNA mismatch repair and abnormal cell growth because of the essential role in the synthesis of DNA. Similarly, in a recently published study, many essential genes, such as ALDOA, PKM, SDS, SDSL, ASS1, POLD3, XDH, and ARG1, in response to folic acid treatment, were documented as being significantly associated with the biosynthesis of amino acid signaling [58]. Moreover, MCM2, MCM3, POLD3, and LIG1 were documented to have an involvement in DNA replication and mismatch repair, while PHOSPHO1, LPCAT2, GPAT2, and GPAT3 were found to control the glycerophospholipid metabolism.…”

“…Pathways are important for sustaining homeostasis within an organism, and the flow of metabolites through a pathway is controlled based on the cell's needs and the substrate's availability. We also noted in our previously published study that the majority of genes demonstrated their importance for the mediation of metabolic signaling, which further speeds up various biological processes related to metabolism [58]. Folic acid acts in the acceptance and release of one-carbon units [27], which are vital for the biosynthesis of purine, pyrimidine, and DNA, and also offers the methyl group for the formation of S-adenosylmethionine.…”

“…Recently, our research team investigated the association of folic acid supplementation alone with milk production and milk variables [58], as shown in Figure 3. Furthermore, it was also observed that the quantity of folic acid plays a role in lactational performance [58]. Note: Overall, Figure 3 shows that treatment in group B was effective for the improvement in milk production.…”

“…Folate metabolism seems to have a vital influence on milk protein synthesis in mammary epithelial cells [66]. Recently, our published study noted that oral supplementation of folic acid significantly regulates milk production in periparturient dairy cows [58]. The effects of folic acid on milk production performance may be due to its correlation with DNA synthesis and the methylation cycle.…”

“…A recent study [58] performed transcriptomic profiling of blood lymphocytes of folic acid-treated periparturient dairy cattle. The findings of the analysis illustrated that folic acid treatment mediated key DEGs (LAP3, SOCS3, BMX, ZC3H12A, UBE2C, MRPL57, BRCA1, IGF1R, LPL, HK3, PKM, VLDLR, XDH, SLC25A25, CTSB, DGAT2, UBE2R2, BRCA1, GGT, CALCRL, SDSL, ALOX5, SPP1, LYZ, and PPARD) that were notably associated with metabolism, milk fat, protein, milk production, and mammary gland development [58]. Cui and colleagues recorded several genes, such as RPL23A, SLC25A38, BMX, and ZC3H14, with a strong correlation with milk fat and protein yield [67].…”