Molecular Basis of Human Sperm Capacitation

Molina, Lis del Carmen Puga; Luque, Guillermina M.; Balestrini, Paula A.; Marı́n-Briggiler, Clara I.; Romarowski, Ana; Buffone, Mariano G.

doi:10.3389/fcell.2018.00072

Cited by 161 publications

(181 citation statements)

References 351 publications

(488 reference statements)

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“…48,49 Cyclic AMP-mediated protein kinase A activation is known to occur during sperm capacitation. 48,49 Cyclic AMP-mediated protein kinase A activation is known to occur during sperm capacitation.…”

Section: Effect Of Fk506 On Protein Phosphorylation During Sperm Camentioning

confidence: 99%

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Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs

et al. 2019

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Glycogen synthase kinase 3 (GSK3) was identified as an enzyme regulating sperm protein phosphatase. The GSK3α paralog, but not GSK3β, is essential for sperm function. Sperm lacking GSK3α display altered motility and are unable to undergo hyperactivation, which is essential for fertilization. Male mice lacking sperm‐specific calcineurin (PP2B), a calcium regulated phosphatase, in testis and sperm, are also infertile. Loss of PP2B results in impaired epididymal sperm maturation and motility. The phenotypes of GSK3α and PP2B knockout mice are similar, prompting us to examine the interrelationship between these two enzymes in sperm. High calcium levels must exist to permit catalytically active calcineurin to function during epididymal sperm maturation. Total and free calcium levels are high in immotile compared to motile epididymal sperm. Inhibition of calcineurin by FK506 results in an increase in the net phosphorylation and a consequent decrease in catalytic activity of sperm GSK3. The inhibitor FK506 and an isoform‐selective inhibitor of GSK3α, BRD0705, also inhibited fertilization of eggs in vitro. Interrelated functions of GSK3α and sperm PP2B are essential during epididymal sperm maturation and during fertilization. Our results should enable the development of male contraceptives targeting one or both enzymes.

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Section: Effect Of Fk506 On Protein Phosphorylation During Sperm Camentioning

confidence: 99%

“…Increased tyrosine and serine phosphorylation of proteins accompany sperm capacitation. 48,49 Cyclic AMP-mediated protein kinase A activation is known to occur during sperm capacitation. 3 We determined tyrosine and PKA-mediated serine phosphorylation in FK506-treated sperm.…”

Section: Effect Of Fk506 On Protein Phosphorylation During Sperm Camentioning

confidence: 99%

Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs

et al. 2019

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“…Other common targets in somatic cells for both gasotransmitters are the Ca 2+ channels [29,35] and K + channels [29,35,59]. The regulation of Ca 2+ currents in sperm is of particular interest, as CatSper are involved not only in sperm capacitation [109], but also in sperm hyperactivation, acrosome reaction, and chemotaxis [53,110]. The hypothesis of NO involvement in chemotaxis through affection of the ion channel function may seem intriguing, as Miraglia et al [111] observed a positive influence of NO on sperm migration.…”

Section: No and H 2 S Interactionsmentioning

confidence: 99%

The Roles of NO and H2S in Sperm Biology: Recent Advances and New Perspectives

Kadlec

Ros-Santaella

Pintus

2020

IJMS

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After being historically considered as noxious agents, nitric oxide (NO) and hydrogen sulfide (H2S) are now listed as gasotransmitters, gaseous molecules that play a key role in a variety of cellular functions. Both NO and H2S are endogenously produced, enzymatically or non-enzymatically, and interact with each other in a range of cells and tissues. In spite of the great advances achieved in recent decades in other biological systems, knowledge about H2S function and interactions with NO in sperm biology is in its infancy. Here, we aim to provide an update on the importance of these molecules in the physiology of the male gamete. Special emphasis is given to the most recent advances in the metabolism, mechanisms of action, and effects (both physiological and pathophysiological) of these gasotransmitters. This manuscript also illustrates the physiological implications of NO and H2S observed in other cell types, which might be important for sperm function. The relevance of these gasotransmitters to several signaling pathways within sperm cells highlights their potential use for the improvement and successful application of assisted reproductive technologies.

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“…At ejaculation, spermatozoa stored in the distal portion of the epididymis mix with the accessory glands secretions and are deposited in the female tract, where they undergo a set of complex and coordinated changes to accomplish fertilization (Satouh & Ikawa, ). Spermatozoa undergo capacitation, a process by which they develop full fertilizing potential, as evidenced by their ability to undergo acrosome reaction and to interact with the oocyte vestments (De Jonge, ; Puga Molina et al , ). Several studies have identified MI phosphoderivatives in sperm mechanisms related to these processes, including progressive and hyperactive motility, sperm guidance, sperm capacitation, acrosome reaction, and sperm–oocyte interactions.…”

Section: Myo‐inositol and Derivates In The Male Reproductive Tractmentioning

confidence: 99%

Myo‐inositol in health and disease: its impact on semen parameters and male fertility

Vazquez‐Levin

Verón

2019

Andrology

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Background Myo‐inositol (cis‐1,2,3,5‐trans‐4,6‐cyclohexanehexol; MI) is the most prominent of nine inositol stereoisomers. MI, its phosphate derivatives, and associated lipids are widely found in vegetables and animal tissues and are known to participate in numerous biological processes. Objectives To perform a review analysis on MI presence, functions, and impact in male fertility. Materials and Methods A thorough search of listed publications in PubMed on MI and its derivatives was done. Results Published information was found and compiled on MI identification, natural dietary sources and absorption, biosynthesis, concentrations, as well as MI as its derivatives (PI, PIP, GPI, IPG) roles in several human tissues and body fluids in health and disease. A section was focused on MI presence, biosynthesis, and functions in the mammalian male genital tract and in spermatozoa, and summarized reports describing the impact of in vivo and in vitro MI supplementation on human semen quality and fertility. Studies reported a discrete improvement in sperm motility in fresh and frozen‐thawed semen, and a better sperm performance in natural and assisted fertility. Discussion and Conclusion MI was reported as an effective supplement for sperm quality. In any case, several study designs lack appropriate controls or data analysis to confirm the relevance of the findings. While promising, larger prospective randomized controlled studies will be required to confirm the positive effect of MI supplementation in male infertility management. Moreover, further investigations are encouraged to unravel MI roles in sperm physiology and the underlying molecular mechanisms.

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Molecular Basis of Human Sperm Capacitation

Cited by 161 publications

References 351 publications

Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs

Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs

The Roles of NO and H2S in Sperm Biology: Recent Advances and New Perspectives

Myo‐inositol in health and disease: its impact on semen parameters and male fertility

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