Regulators of sperm function: A role for diacylglycerol in human sperm acrosomal exocytosis

O'Toole, Christine M.B.; Roldán, Eduardo R. S.; Hampton, Paul M.; Fraser, Lynn R.

doi:10.1093/molehr/2.5.317

Cited by 45 publications

(24 citation statements)

References 39 publications

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“…Indeed, the increase in cAMP concentrations following P stimulation is very low (Parinaud and Milhet, 1996), raising doubts about the relevance of the pathway in the response to the steroid. A similar situation applies for the phospholipase C/inositol3phosphate/diacylglycerol/protein kinase (PLC/IP3/DAG/PKC) pathway: although the enhancing effect of P on inositol trisphophate (Thomas and Meizel, 1989) and diacylglycerol (O'Toole et al, 1996a) synthesis has been reported, blockers of phospholipase C do not appear to affect P-stimulated Ca 2+ fluxes (Harper et al, 2004), and whether the pathway is involved in the induction of AR remains controversial (O'Toole et al, 1996b;Bonaccorsi et al, 1998). P at micromolar concentrations has been also shown to promote tyrosine phosphorylation of sperm proteins (Tesarik et al, 1993;Luconi et al, 1995) and this pathway is involved in AR and Ca 2+ influx in response to the steroid (Martinez et al, 1999;Bonaccorsi et al, 1995).…”

Section: P-induced Acrosome Reactionmentioning

confidence: 98%

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

Baldi

Luconi

Muratori

et al. 2009

Molecular and Cellular Endocrinology

139

154

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a b s t r a c tThe rapid effects of steroids on spermatozoa have been demonstrated for the first time two decades ago. Progesterone (P), which is present throughout the female genital tract with peaks of levels in the cumulus matrix surrounding the oocyte, stimulates several sperm functions, including hyperactivation and acrosome reaction. These effects are mediated by an extranuclear pathway, as P stimulates an influx of calcium, the tyrosine phosphorylation of sperm proteins and other signalling cascades in a rapid manner. Whether these effects are receptor mediated and which receptors mediate these effects are still a matter of discussion despite all the efforts of the scientific community aimed at identifying them during the last 20 years. Although responsiveness to P is related to sperm fertilizing ability, the physiological role of P during the process of fertilization is discussed, and recent evidence points for a role of the steroid as a chemotactic agent for sperm. A similar situation applies for estrogens (E), which have been shown to induce direct effects on sperm by an extranuclear pathway. In particular, E appear to decrease acrosome reaction in response to P, exerting a role in ensuring an appropriate timing for sperm exocytosis during the process of fertilization.

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Section: P-induced Acrosome Reactionmentioning

confidence: 98%

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

Baldi

Luconi

Muratori

et al. 2009

Molecular and Cellular Endocrinology

139

154

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“…This leads to phospholipase C (PLC) activation which converts phosphatidyl inositol bisphosphate to diacylglycerol and inositol trisphosphate (O'Toole et al, 1996). The latter is involved in sperm capacitation and AR (Breitbart and Spungin, 1997).…”

Section: © European Society Of Human Reproduction and Embryologymentioning

confidence: 99%

Pentoxifylline-stimulated capacitation and acrosome reaction in hamster spermatozoa: involvement of intracellular signalling molecules

Ain

Devi²,

Shivaji³

et al. 1999

Molecular Human Reproduction

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We investigated the role of cAMP/cGMP, protein kinases and intracellular calcium ( [Ca 2⍣ ] i ) in pentoxifyllinestimulated hamster sperm capacitation and the acrosome reaction (AR) in vitro. Treatment with pentoxifylline (0.45 mM) initially increased sperm cAMP values 2.8-fold, compared with untreated controls (396 ⍨ 9.2 versus 141 ⍨ 6.0 fmoles/10 6 spermatozoa; mean ⍨ SEM, n ⍧ 6) after 15 min, although by 3 h, cAMP values were similar (503-531 fmoles/10 6 spermatozoa). cGMP values (~27 fmoles/10 6 spermatozoa) were the same in treated and control spermatozoa. Both sperm capacitation and the AR, determined from the absence of an acrosomal cap, were stimulated by pentoxifylline; these were almost completely inhibited by a Cl -/ HCO 3 -antiporter inhibitor (4,4-diisothiocyanato-stilbene-2,2 disulphonic acid; 1 mM) defined from the degree of sperm motility and by a protein kinase A inhibitor (H89; 10 µM). A protein kinase C inhibitor (staurosporine, 1 nM) did not affect pentoxifylline-stimulated capacitation but inhibited the AR by 50%. A protein tyrosine kinase inhibitor (tyrphostin A-47, 0.1 mM) had no effect on either pentoxifylline-stimulated capacitation or AR. A phospholipase A 2 inhibitor (aristolochic acid, 0.4 mM) markedly inhibited the pentoxifylline-stimulated AR but not capacitation. When intracellular sperm calcium [Ca 2⍨ ] i was measured using fura-2-AM, there was an early rise (271 nM at 0.5 h) in pentoxifylline-treated spermatozoa; this appeared to be due to intracellular mobilization rather than to uptake. In the absence of extracellular Ca 2ϩ , sperm motility was maintained in the presence of pentoxifylline, but capacitation did not occur; spermatozoa exhibited a low level of hyperactivated motility and had a poor rate of AR (20.5 ⍨ 2.3%). These results suggest that: (i) the pentoxifylline-stimulated early onset of sperm capacitation may be mediated by an early rise in cAMP and [Ca 2⍨ ] i and involves protein kinase A activity; and (ii) pentoxifylline-stimulated AR may require phospholipase A 2 and protein kinase C activity.

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“…Treatment with these agonists, including A23187/Ca 2+, results in a rapid generation of diacylglycerol (DAG) due to the hydrolysis of polyphosphoinositides by phosphoinositidase C [3,[6][7][8] and hydrolysis of phosphatidylcholine by a specific phospholipase C [3,8,9]. No evidence for the participation of the phospholipase D/phosphatidic acid phosphohydrolase pathway in the generation of DAG has been found [3].…”

Section: Introductionmentioning

confidence: 99%

rab3‐Peptide stimulates exocytosis of the ram sperm acrosome via interaction with cyclic AMP and phospholipase A₂ metabolites

Garde

Roldán

1996

FEBS Letters

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Aerosomal exocytosis triggered with A23187/Ca 2+ was enhanced by rab3AL, a synthetic peptide corresponding to the effector domain of the small GTP-binding protein rab3. Exocytosis was further enhanced when spermatozoa were also exposed to dihutyryl-cAMP, but was prevented when H-89, a protein kinase A (PKA) inhibitor, was included. The action of rab3AL was not on, or upstream of, phospholipase A2 (PLA2). Inhibition of exocytosis by the PLA2 inhibitor aristolochic acid was overcome by rab3AL when it was included together with lysophosphatidylcholine; this effect was prevented by H-89. These results suggest a functional coupling between rab3 protein, metabolites generated by PLA2, and cAMP-activated PKA, in the final steps leading to membrane fusion during acrosomal exocytosis.Key words: Exocytosis; rab3; Phospholipase Az; Lysophosphatidylcholine; cAMP; Spermatozoa that regulate docking and fusion of secretory granules with the plasma membrane [16][17][18][19].Synthetic peptides corresponding to a putative effector domain of rab3 proteins have been shown to stimulate exocytosis in permeabilized [20 23] and intact cells [24], and membrane fusion in a cell-free assay system [25]. We have therefore used a sperm model system, where cells are stimulated to undergo exocytosis with A23187/Ca 2+, to explore whether rab3 might be involved in the final steps of membrane fusion during acrosomal exocytosis. We present, for the first time, evidence suggesting that rab3 protein, together with PLA2-derived metabolites and the cAMP/PKA signalling pathway, play an important role during the final steps of acrosomal exocytosis in mammalian spermatozoa. Materials and methods

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Regulators of sperm function: A role for diacylglycerol in human sperm acrosomal exocytosis

Cited by 45 publications

References 39 publications

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

Pentoxifylline-stimulated capacitation and acrosome reaction in hamster spermatozoa: involvement of intracellular signalling molecules

rab3‐Peptide stimulates exocytosis of the ram sperm acrosome via interaction with cyclic AMP and phospholipase A₂ metabolites

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Regulators of sperm function: A role for diacylglycerol in human sperm acrosomal exocytosis

Cited by 45 publications

References 39 publications

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

Pentoxifylline-stimulated capacitation and acrosome reaction in hamster spermatozoa: involvement of intracellular signalling molecules

rab3‐Peptide stimulates exocytosis of the ram sperm acrosome via interaction with cyclic AMP and phospholipase A2 metabolites

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rab3‐Peptide stimulates exocytosis of the ram sperm acrosome via interaction with cyclic AMP and phospholipase A₂ metabolites