Ergot alkaloids induce vasoconstriction of bovine uterine and ovarian blood vessels

Abstract

Fescue toxicosis is a syndrome that impairs growth and reproduction in cattle grazing endophyte-infected tall fescue [Lolium arundinaceum [(Schreb.].) Darbysh)] in the United States, resulting in approximately $1 billion in annual economic loss in species that utilize this forage resource. Approximately 90% of tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids. Ergot alkaloids cause vasoconstriction and reduced blood flow to the extremities; however, it remains unknown how blood flow to the reproductive organs is affected in cattle. Therefore, the objective of this study was to determine if ergot alkaloids from endophyte-infected tall fescue reduce blood flow to the reproductive organs, thus hindering reproductive function. Angus heifers (n = 36) naïve to ergot alkaloids were placed in Calan gates and randomly assigned to receive either endophyte-infected fescue seed (E+) or noninfected fescue seed (E-; control) in a total mixed ration for 63 d. Weekly measurements were taken to monitor heifer growth and response to ergot alkaloid exposure. Reproductive measurements, including ovarian structures, uterine and ovarian vessel diameter, and hormone concentrations were determined after heifers were synchronized using the standard CO-Synch + 7 d CIDR protocol to ensure all measurements were collected at the same stages of the estrous cycle (0, 4, 10, and 17 d). Data were analyzed using repeated measures in PROC MIXED of SAS. Average daily gain was decreased for the E+ group (0.8 kg/d) compared to control heifers (1.0 kg/d). Body condition scores tended to be greater in control heifers compared to the E+ group (P = 0.053). Additionally, hair coat and hair shedding scores were greater in E+ heifers compared to controls (P < 0.05). Heart rate, rectal temperature, respiration rate, and blood pressure did not differ between treatments (P > 0.05). Vasoconstriction was observed in the caudal artery, but not the caudal vein, in heifers consuming the E+ fescue seed (P < 0.05). No differences were observed in antral follicle counts, corpus luteum area or circulating progesterone concentrations in E+ heifers compared to controls (P > 0.05). There was a significant decrease in the diameter of arteries and veins servicing the ovary and uterus on day 10 and 17 of the estrous cycle. Reduction in blood flow to the reproductive organs during critical times in the estrous cycle may contribute to the reduced ovarian function and pregnancy rates associated with fescue toxicosis.

Ergot alkaloid exposure during gestation alters. I. Maternal characteristics and placental development of pregnant ewes1

“…Additionally, ergot alkaloids have been known to cause contractile responses in a variety of vessels and species such as the lateral saphenous veins in cattle, the distal palmar artery of horses, the carotid and auricular arteries in goats, tail arteries in rats, and iliac arteries of guinea pigs (Schoning et al, 2001;Klot et al, 2007;McDowell et al, 2013;Aiken and Flythe, 2014). It was also documented that heifers exposed to E+ fescue exhibited reductions in the uterine vein and artery (and ovarian vein and artery) during the later stages of the estrous cycle (Poole et al, 2018). This further supported the conclusion made by Dyer (1993) that ergovaline, specifically, is a potent vasoconstrictor in the bovine umbilical and uterine arteries and has the potential to directly impair blood flow to the uterus and developing placenta during gestation.…”

Impact of Ergot Alkaloids on Female Reproduction in Domestic Livestock Species

“…Similarly, ergot alkaloids have a high affinity towards α 2 -adrenergic receptors [47,48]. Additionally, a couple of studies have used Doppler ultrasonography to show that heifers chronically exposed to endophyte-infected tall fescue have reduced caudal artery area and blood flow to the peripheral arteries when compared to heifers consuming endophyte-free tall fescue [49,50], however literature describing the extent to which vasoconstriction occurs to the internal organs is limited [16].…”

Identification of differentially expressed genes for fescue toxicosis in high and low tolerant Angus cows

“…Reduced blood to the periphery might cause hypoxemia resulting in subsequent increase in respiration rates, which is a known symptom in cattle experiencing FT [54]. In humans, Vecchione et al [52] found that BPIFB4 is a powerful enhancer for endothelial vasorelaxation and revascularization, further supporting its potential role in FT. WNT11 has several functions, such as promotion of cardiomyocyte differentiation, activation of kinase activity, and osteoblast maturation [55].…”