Defective protein kinase A and C pathways are common causes of disordered zona pellucida (ZP)–induced acrosome reaction in normozoospermic infertile men with normal sperm-ZP binding

Liu, Deyi; Zhao, Shuo; Baker, H. W. G.

doi:10.1016/j.fertnstert.2012.08.040

Cited by 11 publications

(6 citation statements)

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“…In agreement with our results, the studies conducted in humans by Liu et al. () show that in normospermic individuals, the prevalent cause of infertility is a failure in signal transduction when PKA is defective, reinforcing the key role played by cAMP‐dependent kinase.…”

Section: Discussionsupporting

confidence: 93%

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A₂ and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Gramajo-Bühler¹,

Zelarayán

Sánchez-Toranzo

2015

Reprod Domestic Animals

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The mechanisms involved in fertilization are the centre of attention in order to determine the conditions required to reproduce in vitro the events that take place in vivo, with special interest in endangered species. Previous data from mouse sperm, where acrosome reaction (AR) occurs more often in the interstitium of the cumulus oophorus, contribute to strengthen the use of progesterone as a physiological inducer of this process. We studied the participation of protein kinase A (PKA), phospholipases A2 and C (PLA2 , PLC) in the AR induced by progesterone from Chinchilla epididymal spermatozoa. The addition of db-cAMP to the incubation medium caused an increase of 58% in the AR, while the use of H89 (30 μm), a PKA inhibitor, reflected a decrease of 40% in the percentage of reacted gametes. The assays conducted with arachidonic acid showed a maximum increase of 23% in the AR. When gametes were pre-incubated with PLA2 inhibitors, a dose-dependent inhibitory effect was observed. The addition of phorbol12-myristate13-acetate (10 μm) revealed higher percentages of AR induction (60%). When PLC was inhibited with neomycin and U73122, a dose-dependent decrease in AR percentages was observed. Combined inhibition of PKA, PLA2 and PLC, AR values similar to control were obtained. This work shows evidence, for the first time in Chinchilla, that progesterone activates the AC/cAMP/PKA system as well as sperm phospholipases and that these signalling pathways participate jointly and cooperatively in AR. These results contribute to the understanding of the complex regulation that is triggered in sperm after the effect of progesterone.

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Section: Discussionsupporting

confidence: 93%

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A₂ and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Gramajo-Bühler¹,

Zelarayán

Sánchez-Toranzo

2015

Reprod Domestic Animals

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“…Activation of PKC can induce acrosome exocytosis in sperm (Breitbart et al, ; Rotem et al, ; Toole et al, ), and key PKC substrates, such as MARCKS protein, play an important role in the process (Rodriguez Peña et al, ). Studies indicate that disruption of PKA and PKC pathways are a major cause of disordered zona pellucida‐induced acrosome reaction in normozoospermic infertile men with normal sperm‐zona pellucida binding (Liu et al, ). Our current data support a physiological role for sperm PKCδ in the regulation of zona pellucida interaction.…”

Section: Discussionmentioning

confidence: 99%

Lack of protein kinase C‐delta (PKCδ) disrupts fertilization and embryonic development

Baumann

Viveiros

2015

Molecular Reproduction Devel

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This study tested the function of protein kinase C delta (PKCδ) during fertilization and embryonic development using gene-knockout (Prkcd(-/-)) mice. Fertility analysis revealed that Prkcd(-/-) mating pairs produce significantly fewer pups per litter than wild-type pairs (P< 0.05), and exhibit a high incidence of embryonic loss post-implantation. Both Prkcd(-/-) male as well as Prkcd(-/-) female mice mated to Prkcd(+/+) controls also showed reduced litter sizes, with a selective loss of Prkcd-null pups. Further analysis of the females demonstrated comparable in vitro fertilization outcomes between control and Prkcd(-/-) oocytes fertilized with wild-type sperm. Pregnant Prkcd(-/-) females, however, exhibited a reduced number of total implantations, suggesting a possible disruption in early embryo quality and/or implantation. In turn, male gamete analysis revealed that Prkcd(-/-) sperm demonstrated a decreased capacity to penetrate the zona pellucida (P < 0.05), necessary for successful fertilization. Moreover, we identified phosphorylated PKCδ as a component of the sperm acrosome, indicating a potential role for this kinase in acrosome exocytosis. Therefore, loss of PKCδ disrupts key reproductive functions in both males and females that limit fertility.

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“…More recently, it was found that MARCKS protein is phosphorylated by PKC during human acrosomal exocytosis (Rodriguez Pena et al, 2013) supporting the role of PKC in acrosomal exocytosis preparation. Also, PKC activity has been involved in early events leading to acrosomal exocytosis in other mammals, and a more recent work demonstrated that PMA enhances ZP-induced Acrosomal reaction (AR) in human sperm (Liu et al, 2013). Despite our previous results (Teijeiro & Marini, 2012), which showed no effect of PMA on boar sperm acrosome reaction, here we demonstrate a slight but significant effect of PMA on acrosome reaction, detected by a more sensitive and Figure 5 Effect of PMA-induced PKC activation and PKA inhibition over changes in plasma membrane lipids organization.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C activity in boar sperm

et al. 2017

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SUMMARYMale germ cells undergo different processes within the female reproductive tract to successfully fertilize the oocyte. These processes are triggered by different extracellular stimuli leading to activation of protein phosphorylation. Protein kinase C (PKC) is a key regulatory enzyme in signal transduction mechanisms involved in many cellular processes. Studies in boar sperm demonstrated a role for PKC in the intracellular signaling involved in motility and cellular volume regulation. Experiments using phorbol 12-myristate 13-acetate (PMA) showed increases in the Serine/Threonine phosphorylation of substrates downstream of PKC in boar sperm. In order to gain knowledge about those cellular processes regulated by PKC, we evaluate the effects of PMA on boar sperm motility, lipid organization of plasma membrane, integrity of acrosome membrane and sperm agglutination. Also, we investigate the crosstalk between PKA and PKC intracellular pathways in spermatozoa from this species. The results presented here reveal a participation of PKC in sperm motility regulation and membrane fluidity changes, which is probably associated to acrosome reaction and to agglutination. Also, we show the existence of a hierarchy in the kinases pathway. Previous works on boar sperm suggest a pathway in which PKA is positioned upstream to PKC and this new results support such model.

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Defective protein kinase A and C pathways are common causes of disordered zona pellucida (ZP)–induced acrosome reaction in normozoospermic infertile men with normal sperm-ZP binding

Abstract: Defective upstream of PKC and PKA pathways are highly associated with disordered ZPIAR in normozoospermic infertile men with normal sperm-ZP binding.

Cited by 11 publications

References 46 publications

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A₂ and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A₂ and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Lack of protein kinase C‐delta (PKCδ) disrupts fertilization and embryonic development

Protein kinase C activity in boar sperm

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Defective protein kinase A and C pathways are common causes of disordered zona pellucida (ZP)–induced acrosome reaction in normozoospermic infertile men with normal sperm-ZP binding

Abstract: Defective upstream of PKC and PKA pathways are highly associated with disordered ZPIAR in normozoospermic infertile men with normal sperm-ZP binding.

Cited by 11 publications

References 46 publications

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A2 and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A2 and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Lack of protein kinase C‐delta (PKCδ) disrupts fertilization and embryonic development

Protein kinase C activity in boar sperm

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Involvement of Protein cAMP‐dependent Kinase, Phospholipase A₂ and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera

Involvement of Protein cAMP‐dependent Kinase, Phospholipase A₂ and Phospholipase C in Sperm Acrosome Reaction of Chinchilla lanigera