Metabolism-associated genome-wide epigenetic changes in bovine oocytes during early lactation

Abstract

Dietary intake in early lactating cows is outmatched by milk production. these cows experience a negative energy balance, resulting in a distinct blood metabolism and poor reproductive function due to impaired ovulation and increased embryo loss. We hypothesize that oocytes from lactating cows undergoing transient metabolic stress exhibit a different epigenetic profile crucial for developmental competence. To investigate this, we collected oocytes from metabolically-profiled cows at early-and mid-postpartum stages and characterized their epigenetic landscape compared with control heifers using whole-genome bisulfite sequencing. Early-postpartum cows were metabolically deficient with a significantly lower energy balance and significantly higher concentrations of non-esterified fatty acids and beta-hydroxybutyrate than mid-postpartum animals and control heifers. Accordingly, 32,990 early-postpartum-specific differentially methylated regions (DMRs) were found in genes involved in metabolic pathways, carbon metabolism, and fatty acid metabolism, likely descriptive of the epigenetic regulation of metabolism in early-postpartum oocytes. DMRs found overlapping cpG islands and exons of imprinted genes such as MEST and GNAS in early-postpartum oocytes suggest that early lactation metabolic stress may affect imprint acquisition, which could explain the embryo loss. This wholegenome approach introduces potential candidate genes governing the link between metabolic stress and the reproductive outcome of oocytes.

Extracellular vesicles shuttle protective messages against heat stress in bovine granulosa cells

“…Interestingly, in the same study, it has been revealed that EVs primed with oxidative stress could rescue cells under oxidative stress conditions and improve their viability. Similarly, EVs obtained from the follicular fluid of cows with divergent metabolic status were found to be loaded with unique miRNA molecular signatures 30 associated with altered the epigenome profile of the accompanying oocytes 40 . Such in vivo studies cannot provide a clear picture of the effect of environmental or physiological stress in specific follicular cells.…”

Extracellular Vesicles as Mediators of Environmental and Metabolic Stress Coping Mechanisms During Mammalian Follicular Development

“…Based on the miRNA fingerprints carried by follicular EVs, cows under positive energy balance post-partum closely resembled heifers than cows under NEB conditions. Moreover, the oocytes derived from these cows during early post-partum showed altered epigenetic profiles compared to those derived during the late post-partum period (103). Interestingly, the study identified around 33,000 differentially methylated regions (DMRs) were found to be specific to early-post-partum and these were located within genes involved in metabolic, carbon metabolism, and fatty acid metabolisms.…”

The Epigenetics of Gametes and Early Embryos and Potential Long-Range Consequences in Livestock Species—Filling in the Picture With Epigenomic Analyses

“…One region, a uniquely differentially methylated CpG island in the early post-partum group specifically mapped to the imprinted gene, MEST . Oocytes collected at the mid post-partum time point were much more similar to control oocytes (in overall methylation level and number of DMRs), indicating a degree of recovery when the cows returned to positive energy status (Poirier et al, 2020 ). Taken together, this work indicates that nutritional stress can impact the methylome of developing gametes, which likely has impacts for gamete viability and developmental potential.…”

“…A follow up IVM experiment found specific effects of non-esterified fatty acids (NEFAs) and NEFAs + SAM on the methylation of PLAGL1 (O'Doherty et al, 2014 ). Recent work expanded on this candidate gene analysis and used WGBS to examine the effects of negative energy balance on the epigenome of in vivo oocytes collected at early (~37 days post-partum) and mid (~65 days post-partum) time points vs. oocytes from heifers (Poirier et al, 2020 ). The oocytes collected during the early negative energy balance period displayed significant methylation variation within the group (3 replicate pools of oocytes); they also had lower methylation levels overall compared with the mid post-partum and control oocytes.…”