Angiotensin II induces acrosomal exocytosis in bovine spermatozoa

Abstract

Ejaculated mammalian spermatozoa must reside in the female genital tract for some time before gaining the ability to fertilize the egg. During this time, spermatozoa undergo some physiological changes that collectively are called capacitation. Capacitation of mammalian spermatozoa is a prerequisite for acrosome reaction, which is an exocytotic event occurring before fertilization. The specific biophysical and biochemical changes that accompany sperm capacitation and the agonists inducing acrosome reaction are not fully understood. Using SDS-gel electrophoresis and immunoblotting, we demonstrate the existence of a class of angiotensin receptors (AT1) in bovine spermatozoa. In capacitated sperm, we show that angiotensin II (ANG II) AT1 receptors are localized in the head and tail, whereas in noncapacitated cells the receptors are localized in the tail only. We find that ANG II markedly stimulates acrosomal exocytosis of capacitated bovine spermatozoa in vitro in a concentration range of 0.1–10 nM. No effect of ANG II was found in noncapacitated cells. The ability of ANG II to stimulate the acrosome reaction depends on the presence of calcium ions in the incubation medium. The ANG II-induced acrosome reaction was markedly inhibited by a selective AT1 receptor antagonist, losartan (DUP 753). PD-123319, a selective antagonist of the ANG II AT2 receptor, had no effect on the ANG II-induced acrosome reaction. Thus ANG II via activation of AT1 receptors may play a regulatory role in the induction of the acrosome reaction.

Modulation of spermatozoon acrosome reaction

“…These effects are produced by the union of Angiotensin II to surface receptors, among which two types have been described, AT 1 and AT 2 (Griendling et al, 1996). Some studies have shown that, in bovines and humans, this hormone can act as an AR inductor by binding to its AT 1 receptor (Gur et al, 1998;Köhn et al, 1998). This AR modulation is dependent on extracellular calcium concentration and can be inhibited by the administration of losartan, a selective AT 1 receptor inhibitor (Vinson et al, 1995;Gur et al, 1998).…”

“…Some studies have shown that, in bovines and humans, this hormone can act as an AR inductor by binding to its AT 1 receptor (Gur et al, 1998;Köhn et al, 1998). This AR modulation is dependent on extracellular calcium concentration and can be inhibited by the administration of losartan, a selective AT 1 receptor inhibitor (Vinson et al, 1995;Gur et al, 1998). The AT 1 receptor is found mainly on the tail of the spermatozoon.…”

Angiotensin II stimulates cAMP production and protein tyrosine phosphorylation in mouse spermatozoa

“…These results are consistent with earlier observations that adenosine initially stimulates capacitation and then inhibits spontaneous acrosome reactions (Green et al 1996), while AII initially stimulates capacitation but subsequently does not inhibit spontaneous acrosome loss . Several papers published recently (bovine, Gur et al (1998); human, Kö hn et al (1998); equine, Sabeur et al (2000)) have reported that AII stimulates the acrosome reaction, but the experimental protocols involved either long or complicated incubations in the presence of AII or preincubation in a cAMP analogue followed by AII. However, the demonstration that AII stimulates cAMP throughout capacitation would be consistent with accumulation of cAMP until a threshold value has been reached that would then stimulate spontaneous acrosome reactions.…”

“…However, AII is also found in seminal plasma at concentrations higher than in blood plasma (O'Mahony et al 2000) and there is evidence that AII receptors of subtype 1 (AT1) are present on mammalian spermatozoa (Vinson et al 1995, Gur et al 1998, Wennemuth et al 1999). More recently, demonstrated that AII, like FPP, adenosine and calcitonin, stimulated capacitation and demonstrable fertilization in vitro in uncapacitated mouse spermatozoa but, unlike those molecules, AII had no inhibitory effects on capacitated cells.…”

Current Concepts of Molecular Events During Bovine and Porcine Spermatozoa Capacitation

“…Lactate [Tsunoda and Chang 1975] Fertilization Promoting Peptide (FPP) [Green et al 1996] -Stimulate capacitation -'First messengers' to capacitation -Prevent spontaneous acrosome reaction Adenosine [Hicks et al 1972] -Acts by regulating AC=cAMP -Possible involvement of G proteins Calcitonin Angiotensin II (AII) [Gur et al 1998] Platelet Activating Factor (PAF) [Roudebush et al 1990] -Signal transduction -Autocrine activation of capacitation -Molecule activation and Ford 2001]. However, uncouplers of oxidative respiration do not affect murine spermatozoa motility and in vitro capacitation [Travis et al 2001].…”