CapacitationIn the 1950's two separate researchers Chang and Austin defined mammalian sperm capacitation as "a period of time that sperm must reside in the female reproductive tract before they acquire the ability to fertilize oocytes". Capacitation is the process of sperm maturation (or activation) that occurs post-ejaculation. Without capacitation sperm have a reduced capacity to fertilize the egg. There are several identifiable changes that occur both on the surface and within the spermatozoa. On the spermatozoa surface, cholesterol efflux occurs along with protein kinase A (PKA)-dependent phosphorylation. Within the spermatozoa, there is an alteration in mitochondrial organization and morphology (More? mitochondria). Several physical characteristics can be used to measure capacitation including: motility (total, progressive and rapid) kinematic parameters of velocity (straight line, mean path, curvilinear) and mean amplitude of lateral head displacement. Finally the measured ability to undergo channel activator (A23187 ionophore) stimulated acrosome reaction. |
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Human Spermatozoa Capacitation (Image: De Jonge C., 2005 reproduced with permission) |
Page Links: Introduction | Some Recent Findings | Capacitation | Human Seminal Plasma | Fertilization Promoting Peptide | Semenogelin | Atrial Natriuretic Peptide | Capacitation-associated Tyrosine-phosphorylated Proteins | Mitochondria | Capacitation in vitro | References | Glossary
Related Pages: Spermatogenesis | Y chromosome | Male | Male Accessory Glands | Puberty | Genital Stage 13/14 Embryo | Genital Stage 22 Embryo | Genital Stage 22 Highpower |
Shimada M, Yanai Y, Okazaki T, Noma N, Kawashima I, Mori T, Richards JS. Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization. Development. 2008 Apr 23;
"...we propose that TLR2 and TLR4 present on cumulus cells were activated by the co-culture with sperm in a hyaluronan fragment-dependent manner, and that chemokines secreted from COCs induced sperm capacitation and enhanced fertilization, providing evidence for a regulatory loop between sperm and COCs during fertilization."
Gur Y, Breitbart H. Mammalian sperm translate nuclear-encoded proteins by mitochondrial-type ribosomes. Genes Dev. 2006 Feb 15;20(4):411-6.
"It is widely accepted that spermatozoa are translationally silent. The present study demonstrates, for the first time, incorporation of labeled amino acids into polypeptides during sperm capacitation, which was completely inhibited by mitochondrial translation inhibitors but not by the cytoplasmic translation inhibitor. .... Thus, contrary to the accepted dogma, nuclear genes are expressed as proteins in sperm during their residence in the female reproductive tract until fertilization."
A number of different factors present in Human seminal plasma (HuSP) (fertilization promoting peptide, adenosine, calcitonin, Heparin binding proteins and angiotensin II) have been shown or suggested to act as initial messengers for capacitation followed by a variety of factors derived from interaction with both cells and factors from the female reproductive tract.
Suggested Capacitation Factors
Seminal plasma appears to have a role in spermatozoa capacitation.
Human Seminal Plasma Heparin binding proteins (HBPs)
Reference: Kumar V, Hassan MI, Kashav T, Singh TP, Yadav S Heparin-binding proteins of human seminal plasma: purification and characterization. Mol Reprod Dev. 2008 Apr 18;
Semenogelin (Sg) and its degradation peptides block sperm capacitation. This seminal vesicle protein initially inhibits spermatozoa motility, and when cleavaged by prostate-specific antigen (PSA) from the prostate spermatozoa movement commences. Semenogelin is also involved with antibacterial activity, hyaluronidase activation and zinc ion shuttling.
Fertilization promoting peptide (FPP), also called Glu2TRH, is a small tripeptide (3 amino acid; pGlu-Glu-Pro-NH2) present in human seminal plasma and other sites. The spermatozoa capacitation effect occurs within 1 hour of exposure. The FPP peptide is a structural analogue to thyrotrophin-releasing hormone (TRH; pGlu-His-Pro-NH2). This peptide also appears in the brain (hippocampus, brain stem and dorsal colliculi) with an unknown role, though it is suggested to act in opposition to the cholinergic action of TRH in the mammalian central nervous. (Nguyen V, etal., 2008) |
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Spermatozoa protein tyrosine phosphorylation appears to be key signaling event in the capacitation process that occurs in the female reproductive tract. It is thought that this acts as a signal to alter mitochondrial function.
Suggested Signal Pathway
capacitation-dependent tyrosine-phosphorylation
phospholipid hydroperoxide glutathione peroxidase (PHGPx) a structural protein of the sperm mitochondrial capsule
alter mitochondrial function.
Reference: Nagdas SK, Winfrey VP, Olson GE. Tyrosine phosphorylation generates multiple isoforms of the mitochondrial capsule protein, phospholipid hydroperoxide glutathione peroxidase (PHGPx), during hamster sperm capacitation. Biol Reprod. 2005 Jan;72(1):164-71.
Atrial Natriuretic Peptide (ANP) also called atrial natriuretic factor(ANF), or atriopeptin has many forms, sources and roles in tissues throughout the body. Reproductively, ANP is found associated with Cumulus Oocyte complex as well as within follicular fluid. ANP does not appear to be involved in capacitation, but following capacitation in the release (exocytosis) of the mammalian spermatozoa acrosome, interestingly this effect is higher in non-capacitated than capacitated spermatozoa. |
Signaling Pathway
Cumulus–Oocyte–Complex ↓ Atrial Natriuretic Peptide ↓ Spermatozoa ↓ Plasma membrane ANP receptor (ANPR-A) activation (guanylyl cyclase-linked receptor) ↓ Formation of guanosine 3',5'-cyclic monophosphate (cGMP) |
Mitochondria Morphology X-ray microscopy has shown that before capacitation mitochondria are compact and tightly wrapped around the axoneme, after capacitation (see figure right) mitochondria are either loosely wrapped around the axoneme or distended. (Vorup-Jensen et al, 1999) X-ray microscopy requires no fixation or modification of the cells as with other techniques avoiding the introduction af artefacts. (modified from Vorup-Jensen et al, 1999.) |
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cAMP-dependent protein kinase (PKAII alpha)
Lin RY, Moss SB, Rubin CS.
Characterization of S-AKAP84, a novel developmentally regulated A kinase anchor protein of male germ cells.
J Biol Chem. 1995 Nov 17;270(46):27804-11.
"In mammalian spermatozoa, most of the type II alpha isoform of cAMP-dependent protein kinase (PKAII alpha) is anchored at the cytoplasmic surface of a specialized array of mitochondria in the flagellar cytoskeleton. This places the catalytic subunits of PKAII alpha in proximity with potential target substrates in the cytoskeleton."
A number of different factors present in seminal plasma (fertilization promoting peptide, adenosine, calcitonin and angiotensin II) have been shown to act as messengers for capacitation.
Studies have also shown that some spermatozoa when capacitated in vitro may "over-capacitate" and undergo spontaneous acrosome reactions.
Brewis IA, Moore HD, Fraser LR, Holt WV, Baldi E, Luconi M, Gadella BM, Ford WC, Harrison RA. Molecular mechanisms during sperm capacitation. Hum Fertil (Camb). 2005 Dec;8(4):253-61. Review.
De Jonge C. Biological basis for human capacitation. Hum Reprod Update. 2005 May-Jun;11(3):205-14.
Articles
Shimada M, Yanai Y, Okazaki T, Noma N, Kawashima I, Mori T, Richards JS. Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization. Development. 2008 Apr 23;
Kumar V, Hassan MI, Kashav T, Singh TP, Yadav S Heparin-binding proteins of human seminal plasma: purification and characterization. Mol Reprod Dev. 2008 Apr 18;
Nguyen V, Zharikova AD, Prokai L. Evidence for interplay between thyrotropin-releasing hormone (TRH) and its structural analogue pGlu-Glu-Pro-NH2 ([Glu2]TRH) in the brain: an in vivo microdialysis study. Neurosci Lett. 2007 Mar 19;415(1):64-7. Nagdas SK, Winfrey VP, Olson GE. Tyrosine phosphorylation generates multiple isoforms of the mitochondrial capsule protein, phospholipid hydroperoxide glutathione peroxidase (PHGPx), during hamster sperm capacitation. Biol Reprod. 2005 Jan;72(1):164-71.
Vorup-Jensen T, Hjort T, Abraham-Peskir JV, Guttmann P, Jensenius JC, Uggerhøj E, Medenwaldt R. X-ray microscopy of human spermatozoa shows change of mitochondrial morphology after capacitation. Hum Reprod. 1999 Apr;14(4):880-4.
Lin RY, Moss SB, Rubin CS.
Characterization of S-AKAP84, a novel developmentally regulated A kinase anchor protein of male germ cells.
J Biol Chem. 1995 Nov 17;270(46):27804-11.
Parinaud J, Milhet P, Vieitez G, Richoilley G. Human sperm capacitation and in-vitro fertilization in a chemically defined and protein-free medium SMART1. Hum Reprod. 1998 Sep;13(9):2579-82.
Chang MC. Chang MC. Fertilizing capacity of spermatozoa deposited into the fallopian tubes. Nature. 1951 Oct 20;168(4277):697-8.
Austin CR. The capacitation of the mammalian sperm. Nature. 1952 Aug 23;170(4321):326.
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