Metabolic and ovarian functions of lactating dairy cows

Reproductive longevity amongst dairy cattle is a hallmark for sustainable dairy production. Nevertheless, subfertility has plagued modern dairy cows. More specifically, failure of cows to physiologically adapt during the transition period can negatively impact subsequent reproductive performance, which is the major cause of involuntary culling in Canadian dairy herds. Although nulliparous heifers are known to have higher reproductive success than their lactating counterparts, there is lack of research investigating the similarities and differences of the metabolic indicators and the oxidative stress markers between nulliparous heifers, primiparous cows, and multiparous cows. Analysis of plasma metabolites revealed that primiparous and multiparous cows have lower levels of circulating glucose, triglycerides, and very low-density lipoprotein and higher levels of total bile acids, total-cholesterol, high-density lipoprotein, low-density lipoprotein, and the ferric reducing ability of plasma compared to nulliparous heifers in the weeks leading up to planned time of breeding. In general, the metabolic profile was drastically altered in multiparous cows where -hydroxybutyric acid levels at one week prior to planned time of breeding was 2-fold higher compared to heifers. We expect that these metabolic profiles were reflected to a large extent in the follicular fluid. Body condition score (BCS) assessment is a management tool to visually appraise lipid mobilization during the transition period. Severe loss of body condition during the transition period until the planned time of breeding has been associated with reduced fertility. Our data showed that cows losing severe body condition had higher levels of circulating non-esterified fatty acids (NEFAs) and ??-glutamyltransferase (GGT) suggesting greater difficulty of liver adaptation to early lactation. These metabolic changes appear to have altered the ovarian follicular microenvironment, since the follicular fluid from the dominant follicle collected at 7 weeks post-partum from cows losing more body condition had lower levels of insulin-like growth factor 1 (IGF1) and estradiol. This is in line with the gene transcription profile of the granulosa cells that was also drastically altered as CYP19A1, NR5A2, IGF1R, and LHCGR transcript levels were lower in cows losing more body condition. Taken together, failure to adapt to early-lactation due to increased lipid mobilization has long-term consequences hindering the development of a competent dominant follicle. To further study the underlying mechanisms of infertility in cattle, we chose to investigate the role of extracellular signal-regulated kinase pathway 1 and 2 (ERK1/2) in bovine ovulation. To study ERK1/2 signaling in vivo for the first time in cattle, we administered PD0325901 (ERK1/2 signaling inhibitor) directly into the dominant follicle of cattle followed by an intramuscular injection of gonadotropin-releasing hormone (GnRH) to stimulate a luteinizing hormone (LH) surge. First, we found that inhibition of ERK1/2 prevented ovulation in cattle. Second, we repeated the experiment collecting the ovary by colpotomy 6h post-GnRH. We then studied global transcriptomics in granulosa cells using RNA-seq technology and established a list of 285 LH-ERK1/2 regulated genes in granulosa cells. In this cohort of genes, we established that EGR1, ADAMTS1, STAT3 and TNFAIP6 expression was drastically decreased in cows treated with PD0325901 + GnRH, where the opposite is true for SLC16A1, which is a monocarboxylate transporter, transporting substances such as -hydroxybutyrate, across the plasma membrane, and no change in STAR expression was observed.Taken together, this thesis provides an insight into the relationship between metabolism and ovarian function in the modern dairy cow.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.