Metabolic and antioxidant status during transition is associated with changes in the granulosa cell transcriptome in the preovulatory follicle in high-producing dairy cows at the time of breeding.

In this study, we hypothesized that early postpartum (pp) metabolic and oxidative stress conditions in dairy cows (particularly those with severe negative energy balance, NEB) are associated with long-term changes in granulosa cell (GC) functions in the preovulatory follicle at the time of breeding. Blood samples were collected at wk 2 and wk 8 pp from 47 healthy multiparous cows. Follicular fluid (FF) and GC were collected from the preovulatory follicle after estrous synchronization at wk 8. Several metabolic and antioxidant parameters were measured in blood and FF, and their correlations were studied. Subsequently, 27 representative GC samples were selected for RNA sequencing analysis. The GC gene expression data of LH-responsive genes and the estradiol:progesterone ratio in FF were used to identify pre- and post-LH surge cohorts. We compared the transcriptomic profile of subgroups of cows within the highest and lowest quartiles (Q4 vs. Q1) of each parameter, focusing on the pre-LH surge cohort (n = 16, at least 3 in each subgroup). Differentially expressed genes (DEG: adjusted P-value < 0.05, 5% false discovery rate) were determined using DESeq2 analysis and were functionally annotated. Blood and FF ß-carotene and vitamin E concentrations at wk 2, but not at wk 8, were associated with the most pronounced transcriptomic differences in the GC, with up to 341 DEG indicative for lower catabolism, increased oxidoreductase activity and signaling cascades that are known to enhance oocyte developmental competence, increased responsiveness to LH, and a higher steroidogenic activity. In contrast, elevated blood NEFA concentrations at wk 2 (and not at wk 8) were associated with a long-term carryover effect detectable in the GC transcriptome at wk 8 (64 DEG). These genes are related to response to lipids and ketones, oxidative stress, and immune responses, which suggests persistent cellular stress and oxidative damage. This effect was more pronounced in cows with antioxidant deficiencies at wk 8 (up to 148 DEG), with more genes involved in oxidative stress-dependent responses, apoptosis, autophagy and catabolic processes, and mitochondrial damage. Interestingly, within the severe NEB cows (high blood NEFA at wk 2), blood antioxidant concentrations (high vs. low) at wk 8 were associated with up to 194 DEG involved in activation of meiosis and other signaling pathways, indicating a better oocyte supportive capacity. This suggests that the cow antioxidant profile at the time of breeding might alleviate, at least in part, the effect of NEB on GC functions. In conclusion, these results provide further evidence that the metabolic and oxidative stress in dairy cows early postpartum can have long-term effects on GC functions in preovulatory follicles at the time of breeding. The interplay between the effects of antioxidants and NEFA illustrated here might be useful to develop intervention strategies to minimize the effect of severe NEB on fertility.

Nutrition and maternal metabolic health in relation to oocyte and embryo quality: critical views on what we learned from the dairy cow model.

Although fragmented and sometimes inconsistent, the proof of a vital link between the importance of the physiological status of the mother and her subsequent reproductive success is building up. High-yielding dairy cows are suffering from a substantial decline in fertility outcome over past decades. For many years, this decrease in reproductive output has correctly been considered multifactorial, with factors including farm management, feed ratios, breed and genetics and, last, but not least, ever-rising milk production. Because the problem is complex and requires a multidisciplinary approach, it is hard to formulate straightforward conclusions leading to improvements on the 'work floor'. However, based on remarkable similarities on the preimplantation reproductive side between cattle and humans, there is a growing tendency to consider the dairy cow's negative energy balance and accompanying fat mobilisation as an interesting model to study the impact of maternal metabolic disorders on human fertility and, more specifically, on oocyte and preimplantation embryo quality. Considering the mutual interest of human and animal scientists studying common reproductive problems, this review has several aims. First, we briefly introduce the 'dairy cow case' by describing the state of the art of research into metabolic imbalances and their possible effects on dairy cow reproduction. Second, we try to define relevant in vitro models that can clarify certain mechanisms by which aberrant metabolite levels may influence embryonic health. We report on recent advances in the assessment of embryo metabolism and meantime critically elaborate on advantages and major limitations of in vitro models used so far. Finally, we discuss hurdles to be overcome to successfully translate the scientific data to the field.

Maximizing fertility and fecundity in the sow

A variety of environmental factors and management practices influences fertility and fecundity in the gilt and sow. By studying the biological processes involved in controlling reproduction and by evaluating how theseprocesses change in response to environment and management, it is possible to develop procedures for enhancing reproduction. Many of the factors that influence fertility exert their influences on the hypothalamic-pituitary-ovarian axis in the pig. The focus of research in our laboratory has been on this axis and how altering management practices influences this axis and in turn alters reproduction. Overall, it is clear that one can use management strategics to improve reproduction, if one understands the mechanisms that need to be influenced in order to effect change