Fibronectin stimulates human sperm capacitation through the cyclic AMP/protein kinase A pathway

Martínez-León, Eduardo; Osycka‐Salut, Claudia; Signorelli, Janetti; Pozo, P.; Perez, Blanca; Kong, Milene; Morales, Patricio; Pérez‐Martínez, Silvina; Díaz, Emilce S.

doi:10.1093/humrep/dev154

Cited by 33 publications

(36 citation statements)

References 90 publications

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“…We previously demonstrated that Fn modulates cAMP levels and PKA activity during human sperm capacitation (Martinez‐Leon et al, ). Here, we determined the effects of capacitation on cAMP levels and PKA activity during the early events of sperm capacitation.…”

Section: Resultsmentioning

confidence: 98%

“…We previously demonstrated that Fn‐mediated effects are specific and triggered by Fn‐integrin α 5 β 1 binding (Martinez‐Leon et al, ). In this study, the results suggest that the CB1 and TRPV1 receptors were indirectly activated through Fn‐integrin α 5 β 1 binding during sperm capacitation.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, an interaction between the endocannabinoid system and Fn was described in both endothelial cells (Waldeck‐Weiermair et al, ) and the central nervous system (Jeske et al, ). In addition, it was observed that Fn and AEA are capable of inducing sperm capacitation independently (Gervasi et al, ; Martinez‐Leon et al, ). Given this background, we first tested whether there was a summative or synergistic effect between both molecules.…”

Section: Discussionmentioning

confidence: 99%

“…The same person processed all semen samples using the same equipment. Analyses of semen volume, pH, sperm concentrations and sperm motility and viability were performed as described previously (Martinez‐Leon et al, ). The mean values for semen parameters are summarized in Supporting Information Table S1.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously demonstrated that Fn induces human sperm capacitation via the cAMP/PKA pathway. Specifically, we observed that Fn enhanced capacitation by regulating cAMP levels, protein kinase A (PKA) enzymatic activity and tyrosine phosphorylation (Martinez‐Leon et al, ). However, it is unclear how Fn exerts these effects in human sperm.…”

Section: Introductionmentioning

confidence: 99%

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Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation

Martínez‐León

Osycka‐Salut

Signorelli

et al. 2019

Molecular Reproduction Devel

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Fibronectin (Fn) enhances human sperm capacitation via the cAMP/PKA pathway, and the endocannabinoid system participates in this process. Moreover, Fn has been linked to endocannabinoid system components in different cellular models, even though no evidence of such interactions in human sperm is available. Normal semen samples were evaluated over a 4‐year period. Our findings suggest that (a) the capacitating effects of Fn were reversed by preincubating the sperm with a cannabinoid receptor 1 (CB1) or transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist ( p < 0.001 and p < 0.05, respectively); (b) cooperation between CB1 and TRPV1 may exist ( p < 0.01); (c) the activity of specific fatty acid amide hydroxylase (FAAH) decreased after 1 min ( p < 0.01) and increased after 60 min ( p < 0.01) of capacitation in the presence of Fn; (d) the effects of Fn on FAAH activity were prevented by preincubating spermatozoa with a protein kinase A (PKA) inhibitor ( p < 0.01); (e) Fn modulated both the cyclic adenosine monophosphate concentration and PKA activity ( p < 0.05) during early capacitation; and (f) FAAH was a PKA substrate modulated by phosphorylation. These findings indicate that Fn stimulates human sperm capacitation via the cAMP/PKA pathway through modulation of the endocannabinoid system. Understanding the functional competence of human spermatozoa is essential for facilitating clinical advances in infertility treatment and for developing novel contraceptive strategies.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation

Martínez‐León

Osycka‐Salut

Signorelli

et al. 2019

Molecular Reproduction Devel

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Proper cytoskeleton α‐tubulin distribution is concomitant to tyrosine phosphorylation during in vitro capacitation and acrosomal reaction in human spermatozoa

et al. 2020

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Spermatozoa motility is a key parameter during the fertilization process. In this context, spermatozoa tyrosine protein phosphorylation and an appropriate cytoskeleton α-tubulin distribution are some of the most important physiological events involved in motility. However, the relationship between these two biomarkers remains poorly defined. Here, we characterized simultaneously by immunocytochemistry the α-tubulin (TUBA4A) distribution and the tyrosine phosphorylation at flagellum before capacitation, during different capacitation times (1 and 4 hr), and after acrosome reaction induction in human spermatozoa. We found that the absence of spermatozoa phosphorylation in tyrosine residues positively and significantly correlated (p < 0.05) with the terminal piece α-tubulin flagellar distribution in all physiological conditions. Conversely, we observed a positive significant correlation (p < 0.01) between phosphorylated spermatozoa and continuous α-tubulin distribution in spermatozoa flagellum, independently of the physiological condition. Similarly, the subpopulation of spermatozoa with tyrosine phosphorylated and continuous α-tubulin increases with longer capacitation times and after the acrosome reaction induction. Overall, these findings provide novel insights into the post-transcriptional physiological events associated to α-tubulin and the tyrosine phosphorylation during fertilization, which present potential implications for the improvement of spermatozoa selection methods.

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Fibronectin From Oviductal Cells Fluctuates During the Estrous Cycle and Contributes to Sperm–Oviduct Interaction in Cattle

Osycka‐Salut

Castellano

Fornes

et al. 2017

J of Cellular Biochemistry

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During the passage of sperm through the oviduct, spermatozoa bind to the oviductal epithelium and form the oviductal reservoir. This interaction keeps the fertilizing capacity of sperm until ovulation-associated signals induce sperm release from the oviductal epithelium, allowing the transit of spermatozoa to the fertilization site. Fibronectin is a glycoprotein from the extracellular matrix that binds to α5β1 receptors. Fibronectin has been found to be expressed in the oviduct, whereas α5β1 has been found to be expressed in the sperm of different species. Fibronectin is involved through α5β1 in sperm functions. The aim of this work was to study the participation of oviductal fibronectin in the regulation of the sperm-oviduct interaction in cattle. We found that oviductal epithelial cells differentially expressed all mRNA splice variants of fibronectin during the estrous cycle. Fibronectin was localized in the apical region of oviductal epithelial cells and fibronectin levels in the oviductal fluid fluctuated during the estrous cycle. Also, bovine spermatozoa expressed α5β1. Using in vitro sperm-oviduct co-cultures, we found that spermatozoa were attached to the oviductal epithelium through α5β1. The incubation of co-cultures with fibronectin induced sperm release from the oviductal cells through α5β1. The sperm population released from oviductal cells by fibronectin was enriched in motile and capacitated spermatozoa. Based on our in vitro culture system results, we propose that fibronectin and α5β1 are involved in the sperm-oviduct interaction. Also, an increase in fibronectin levels in the oviductal fluid during the pre-ovulatory period may promote sperm release from the oviductal epithelium in cattle. J. Cell. Biochem. 118: 4095-4108, 2017. © 2017 Wiley Periodicals, Inc.

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Fibronectin stimulates human sperm capacitation through the cyclic AMP/protein kinase A pathway

Abstract: This study was supported by grants from FONDECYT (1130341, E.S.D. and 1120056, P.M.) and FONCYT (PIP 2011-0496, S.P.-M). The authors have no conflicts of interest.

Cited by 33 publications

References 90 publications

Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation

Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation

Proper cytoskeleton α‐tubulin distribution is concomitant to tyrosine phosphorylation during in vitro capacitation and acrosomal reaction in human spermatozoa

Fibronectin From Oviductal Cells Fluctuates During the Estrous Cycle and Contributes to Sperm–Oviduct Interaction in Cattle

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