Involvement of signaling pathways in bovine sperm motility, and effect of ergot alkaloids

Abstract

There is evidence that ergot alkaloids can directly interact with mammalian spermatozoa affecting sperm functions. Ergot alkaloids exert their toxic or pharmaceutical effects through membrane receptor-mediated activities. This study investigated the signaling pathways involved in the in vitro inhibitory effects of both ergotamine (ET) and dihydroergotamine (DEHT) on the relative motility of bovine spermatozoa using specific inhibitors. Motile bovine spermatozoa were prepared using a Percoll gradient and incubated with ergot alkaloids with and without signaling pathway inhibitors. Co-incubation of ET or DHET with 100 microM prazosin (alpha 1-adrenergic receptor inhibitor) decreased (p < 0.05) relative motility of spermatozoa when compared with controls. In addition, preincubation of spermatozoa with 10 or 20 microM prazosin and DHET also reduced (p < 0.05) the number of motile spermatozoa. Relative sperm motility (motility of treated spermatozoa normalized to control sperm motility) was increased (p < 0.05) when co-incubations included ET and yohimbine (alpha 2-adrenergic receptor inhibitor); conversely, co-incubation of yohimbine (100 microM) and DHET decreased (p < 0.05) the percentage of motile spermatozoa when compared with controls. Pertussis toxin and cholera toxin (effectors of inhibitory and stimulatory G-proteins, respectively) altered (p < 0.05) relative sperm motility in a concentration dependent manner; however, co-incubation of pertussis or cholera toxin with ergot alkaloids had no interactive (p = 0.83) effects on the relative motility of spermatozoa. Co-incubation of Rp-cAMP (a membrane-permeable cAMP inhibitor) with 50 microM DHET had no effect (p > 0.05) on relative sperm motility; whereas, the co-incubation of 22.4 or 44.8 microM Rp-cAMP with 50 microM ET increased (p < 0.05) the percentage of motile spermatozoa when compared with 0 or 224 microM Rp-cAMP (49%, 65%, 59%, and 54%, respectively, for 0, 22.4, 44.8, and 224 microM of Rp-cAMP. An interaction between BAPTA-AM (a chelator of intracellular calcium) and alkaloids also impacted (p < 0.05) relative sperm motility. Generally, co-incubating spermatozoa with BAPTA-AM and ET increased the percentage of motile spermatozoa; however, co-incubation with DHET decreased relative sperm motility except with 41 microM BAPTA-AM. Collectively, these observations suggest that ET and DHET decreased the percentage of motile bovine spermatozoa via alpha adrenergic receptors. However, the second messenger systems involved with ergot alkaloid inhibition of relative motility of bovine spermatozoa remain to be elucidated.

BOARD-INVITED REVIEW: St. Anthony's Fire in livestock: Causes, mechanisms, and potential solutions1,2

“…Ergotamine and dihydroergotamine reportedly inhibited sperm motility in a dosedependent manner (Wang et al, 2009), and ergotamine tartrate decreased the ability of sperm to fertilize bovine oocytes (Schuenemann et al, 2005c). Wang et al (2009) suggested that ergotamine and dihydroergotamine decreased the percentage of motile bovine spermatozoa via a-adrenergic receptors with G-protein signaling pathways, with cAMP and intracellular calcium having a passive role in altering sperm motility. Whole animal studies investigating ergot alkaloid effects on sperm characteristics have been less decisive than in vitro research.…”

Management Strategies for Cattle Grazing Toxic Tall Fescue During Summer Months

“…Tall fescue toxicosis is usually more detrimental to animal performance during extreme temperatures (15). It appears from our animal study (13), as well as the laboratory experiment (24), sperm motility is reduced when exposed to ergot alkaloids commonly found in toxic tall fescue plants. The general rule is 1 bull for 20 to 25 cows during the breeding season.…”

Effect of Feeding Fescue Seed Containing Ergot Alkaloid Toxins on Stallion Spermatogenesis and Sperm Cells

“…Clinically, chilled and frozen sperm cells would be more fragile and less fertile. Toxic ergot alkaloids can induce motility changes in bull sperm cells through alpha‐adrenergic receptors (Wang et al. 2009).…”

“…The reported fiscal impact of ergot alkaloids is in the tens and hundreds of millions of dollars. The greatest clinical and financial impact is in the beef industry, with cattle being affected with a number of pathologies (Burfening 1973;Peters et al 1992;Porter and Thompson 1992;Aldrich et al 1993;Dyer 1993;Porter 1993;Hill et al 1994Hill et al , 2000Oliver et al 1994;Cheeke 1995;Schneider et al 1996;Stuedemann et al 1998;Schultze et al 1999;Schnitzius et al 2001;Parish et al 2003;Matthews et al 2005;Realini et al 2005;Wang et al 2009). The symptoms in cattle include increased respiration rates, increased rectal temperatures, salivation, nervousness and rough hair coats, decreased weight gains and decreased overall performance in beef steers (Hoveland 1993).…”

“…Clinically, chilled and frozen sperm cells would be more fragile and less fertile. Toxic ergot alkaloids can induce motility changes in bull sperm cells through alphaadrenergic receptors (Wang et al 2009). Ergot alkaloids have also been shown to induce abnormal proliferation in bovine vascular smooth muscle cells resulting in diminished blood flow to organs.…”