Research articleEffects of rumen-protected methionine and choline supplementation on the preimplantation embryo in Holstein cows
Introduction
Studies over the last 2 decades clearly established the link between nutrition and fertility in ruminants [1], [2], [3], [4], [5]. Dietary changes can cause an immediate and rapid alteration in a range of humoral factors that can alter endocrine and metabolic signaling pathways crucial for reproductive function [6], [7]. Moreover, periconceptional nutritional environment in humans and other animals is critical for the long-term setting of postnatal phenotype [8]. Restricting the supply of B-vitamins and methionine during the periconceptional period in sheep, e.g., resulted in adverse cardiometabolic health in postnatal offspring [9]. Feeding female mice a low-protein diet during the preimplantation period of pregnancy resulted in a reduction in amino acid (AA) concentration in uterine fluid and serum and attendant changes in the AA profile of the blastocyst [10].
Strategies have been used to improve the reproductive performance of dairy cows through alteration of nutritional status [11], [12]. In other species, dietary supplementation with specific AAs (e.g., arginine, glutamine, leucine, glycine, and methionine) had beneficial effects on embryonic and fetal survival and growth through regulation of key signaling and metabolic pathways [13], [14].
Methionine is the most limiting AA in lactating cows [15], but supplementation of diets with crystalline methionine has been excluded because free methionine is quickly and almost totally degraded by the microorganisms in the rumen [15]. In contrast, supplementing rumen-protected methionine (RPM) has a positive effect on milk protein synthesis in dairy cows [16], [17], [18]. Although the role of methionine in bovine embryonic development is unknown, there is evidence that methionine availability alters the transcriptome of bovine preimplantation embryos in vivo [19].
The DNA methylation in promoters is an important mechanism for regulation of gene expression and gene silencing. However, DNA methylation in other regions may have a more complex role in regulation of transcription [20], [21], [22]. Methylation of the DNA depends on the availability of methyl donors supplied by AAs such as methionine and by compounds of one-carbon metabolic pathways such as choline [21]. Increased methionine bioavailability is likely to increase the entry of methionine into the one-carbon metabolism cycle where it is initially converted into S-adenosylmethionine, the major biological methyl donor [23].
Choline is a major component of phospholipids, and sphingomyelin, a component of acetylcholine that participates directly in neurotransmission [24], affects membrane integrity and alters methylation pathways [25], [26]. Early studies evaluating the effect of dietary choline on milk yield and duodenal flow indicated its rapid and extensive rumen degradation before absorption in duodenum [27], [28]. Subsequently, numerous studies have evaluated the effects of feeding rumen-protected choline (RPC) on reproduction and health of dairy cows [29], [30].
Nonruminants fed diets deficient in methyl donors (e.g., choline and methionine) have hypomethylated DNA [31], [32]. These changes occur not only in global methylation [33] but also in the methylation of specific genes [34]. However, effects of methionine in preimplantation embryos are still controversial. Bonilla et al. [35] suggested that extracellular methionine is not required for DNA methylation in the cultured blastocyst. Nevertheless, gene expression changes caused by alteration of DNA methylation (i.e., absence of the methylase genes) can result in embryo death or developmental defects in preimplantation embryos [36].
The hypothesis of the present study was that dietary supplementation with RPM and RPC, or both, increases DNA methylation in preimplantation embryos in dairy cows and is beneficial to embryonic development. The objective of this study was to determine the effects of methionine and choline on DNA methylation and lipid accumulation in preimplantation embryos of Holstein cows.
Section snippets
Materials and methods
The Institutional Animal Care and Use Committee from the University of Illinois (Urbana-Champaign, IL, USA) approved all procedures performed in this experiment.
Results
The ingredient composition of the diets fed to cows is detailed in Table 1 and the analyzed chemical composition is shown in Table 2. Body weight and DMI were not affected by treatment (P > 0.17) at any time in the experiment. Values for BW were as follows: week: −3 to 0 = 770.6 kg (range: 765.6–786.2), week 1 to 4 = 675.8 kg (range: 660.5–702.5 kg), and week 5 to 10 = 640.3 kg (range: 612.7–655.7). Values for DMI were: −3 to 0 = 13.7 kg/d (range: 12.7–14.7), week 1 to 4 = 18.2 kg/d (range:
Discussion
The aim of this study was to determine the effects of RPM and RPC on development, DNA methylation, and lipid accumulation in preimplantation embryos of Holstein cows. We postulated that methionine and choline supplementation would impact the preimplantation embryo in a way that enhanced its capacity for survival so that reproductive function would be enhanced. However, neither treatment affected embryonic survival or cell number; choline also had no effect on DNA methylation or lipid
Acknowledgments
This project was supported in part by a grant from Adisseo USA. Special appreciation is extended to the staff of the University of Illinois Dairy Research Unit; Dr. Glaucio Lopes and Accelerated Genetics for providing the bull sire doses; and Dr. Richard Wallace and Zoetis for providing CIDR, Factrel, and Lutalyse used in this project.
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