Effects of lactoferrin, a protein present in the female reproductive tract, on parameters of human sperm capacitation and gamete interaction

Mammalian spermatozoa acquire their fertilizing ability in the female reproductive tract (sperm capacitation). On the other hand, seminal vesicle secretion, which is a major component of seminal plasma, inhibits the initiation of sperm capacitation (capacitation inhibition) and reduces the fertility of the capacitated spermatozoa (decapacitation). There are seven major proteins involved in murine seminal vesicle secretion (SVS1-7), and we have previously shown that SVS2 acts as both a capacitation inhibitor and a decapacitation factor, and is indispensable forin vivofertilization. However, the effects of SVSs other than SVS2 on the sperm have not been elucidated. Since mouseSvs2–Svs6genes evolved by gene duplication belong to the same gene family, it is possible that SVSs other than SVS2 also have some effects on sperm capacitation. In this study, we examined the effects of SVS3 and SVS4 on sperm capacitation. Our results showed that both SVS3 and SVS4 are able to bind to spermatozoa, but SVS3 alone showed no effects on sperm capacitation. On the other hand, SVS4 acted as a capacitation inhibitor, although it did not show decapacitation abilities. Interestingly, SVS3 showed an affinity for SVS2 and it facilitated the effects of SVS2. Interaction of SVS2 and spermatozoa is mediated by the ganglioside GM1 in the sperm membrane; however, both SVS3 and SVS4 had weaker affinities for GM1 than SVS2. Therefore, we suggest that separate processes may cause capacitation inhibition and decapacitation, and SVS3 and SVS4 act on sperm capacitation cooperatively with SVS2.

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119. IDENTIFICATION AND CHARACTERISATION OF SURFACE PROTEIN COMPLEXES IN HUMAN SPERMATOZOA

Reproduction Fertility and Development ◽

10.1071/srb10abs119 ◽

2010 ◽

Vol 22 (9) ◽

pp. 37 ◽

Cited By ~ 1

Author(s):

K. A. Redgrove ◽

B. Nixon ◽

E. A. McLaughlin ◽

M. K. O'Bryan ◽

R. J. Aitken

Keyword(s):

Zona Pellucida ◽

Reproductive Tract ◽

Protein Complexes ◽

Polyacrylamide Gel Electrophoresis ◽

Human Sperm ◽

Female Reproductive Tract ◽

Human Spermatozoa ◽

Apical Region ◽

Post Translational Modification ◽

Cellular Mechanisms

A unique characteristic of mammalian spermatozoa is that upon ejaculation, they are unable to recognise and bind to an ovulated oocyte. These functional attributes are only realised following the sperms ascent of the female reproductive tract whereupon they undergo a myriad of biochemical and biophysical changes collectively referred to as ‘capacitation’. Since spermatozoa are both transcriptionally and translationally quiescent cells, this functional transformation must be engineered by a combination of post-translational modification and spatial reorganisation of existing sperm proteins. Indeed, evidence from our laboratory suggests that a key attribute of capacitation is the remodeling of the sperm surface architecture leading to the assembly and / or presentation of multimeric sperm-oocyte receptor complex(es). Through the novel application of Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE), we have secured the first direct evidence that human spermatozoa express a number of these protein complexes on their surface. Furthermore, we have demonstrated that a subset of these complexes harbour putative zona adhesion proteins and display strong affinity for solubilised zona pellucidae. In this study, we have extended our findings through the characterisation of one such complex containing arylsulfatase A (ASA), a protein with recognised affinity for sulfated ligands present within the zona pellucida. Through the application of immunohistochemistry and flow cytometry we revealed that ASA undergoes a capacitation-associated translocation to become expressed on the apical region of the human sperm head, a location compatible with a role in the mediation of sperm-zona pellucida interactions. This dramatic relocation was completely abolished by incubation of capacitating spermatozoa in exogenous cholesterol, suggesting that it may be driven in part by alteration in the membrane fluidity characteristics. Our current research is focused on confirming the role of ASA in human sperm-zona pellucida adhesion and elucidating the precise cellular mechanisms that underpin the proteins translocation to the cell surface.

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Human sperm uses asymmetric and anisotropic flagellar controls to regulate swimming symmetry and cell steering

Science Advances ◽

10.1126/sciadv.aba5168 ◽

2020 ◽

Vol 6 (31) ◽

pp. eaba5168 ◽

Cited By ~ 6

Author(s):

Hermes Gadêlha ◽

Paul Hernández-Herrera ◽

Fernando Montoya ◽

Alberto Darszon ◽

Gabriel Corkidi

Keyword(s):

High Speed ◽

Reproductive Tract ◽

Three Dimensional ◽

Human Sperm ◽

Bilateral Symmetry ◽

Female Reproductive Tract ◽

Optical Illusion ◽

3D Microscopy ◽

Molecular Components ◽

Molecular Asymmetries

Flagellar beating drives sperm through the female reproductive tract and is vital for reproduction. Flagellar waves are generated by thousands of asymmetric molecular components; yet, paradoxically, forward swimming arises via symmetric side-to-side flagellar movement. This led to the preponderance of symmetric flagellar control hypotheses. However, molecular asymmetries must still dictate the flagellum and be manifested in the beat. Here, we reconcile molecular and microscopic observations, reconnecting structure to function, by showing that human sperm uses asymmetric and anisotropic controls to swim. High-speed three-dimensional (3D) microscopy revealed two coactive transversal controls: An asymmetric traveling wave creates a one-sided stroke, and a pulsating standing wave rotates the sperm to move equally on all sides. Symmetry is thus achieved through asymmetry, creating the optical illusion of bilateral symmetry in 2D microscopy. This shows that the sperm flagellum is asymmetrically controlled and anisotropically regularized by fast-signal transduction. This enables the sperm to swim forward.

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Mobilisation of Ca2+ stores and flagellar regulation in human sperm by S-nitrosylation: a role for NO synthesised in the female reproductive tract

Development ◽

10.1242/dev.024521 ◽

2008 ◽

Vol 135 (22) ◽

pp. 3677-3686 ◽

Cited By ~ 29

Author(s):

G. Machado-Oliveira ◽

L. Lefievre ◽

C. Ford ◽

M. B. Herrero ◽

C. Barratt ◽

...

Keyword(s):

Reproductive Tract ◽

Human Sperm ◽

Female Reproductive Tract

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In vivo exposure to 17β-estradiol triggers premature sperm capacitation in cauda epididymis

Reproduction ◽

10.1530/rep-12-0472 ◽

2013 ◽

Vol 145 (3) ◽

pp. 255-263 ◽

Cited By ~ 14

Author(s):

Lukas Ded ◽

Natasa Sebkova ◽

Martina Cerna ◽

Fatima Elzeinova ◽

Pavla Dostalova ◽

...

Keyword(s):

Reproductive Tract ◽

Negative Impact ◽

Reproductive Potential ◽

Female Reproductive Tract ◽

Sperm Capacitation ◽

Epididymal Sperm ◽

Knock Out ◽

17Β Estradiol

Estrogens play a crucial role in spermatogenesis and estrogen receptor α knock-out male mice are infertile. It has been demonstrated that estrogens significantly increase the speed of capacitation in vitro; however this may lead to the reduction of reproductive potential due to the decreased ability of these sperm to undergo the acrosome reaction. To date the in vivo effect of estrogens on the ability of sperm to capacitate has not been investigated. Therefore, in this study, we exposed mice (n=24) to 17β-estradiol (E2) at the concentration of 20 ng/ml either during puberty from the fourth to seventh week of age (n=8), or continuously from birth for a period of 12 weeks (n=8) at which age the animals from both groups were killed. The capacitation status of epididymal and testicular sperm was analysed by tyrosine phosphorylation (TyrP) antibody (immunofluorescence and western blot) and chlortetracycline (CTC) assay. According to our results, in vivo exposure to increased E2 concentrations caused premature sperm capacitation in the epididymis. The effect of E2, however, seems reversible because after the termination of the exposure premature epididymal sperm capacitation is decreased in animals treated during puberty. Furthermore the changes in epididymal sperm capacitation status detected by TyrP and CTC positively correlate with plasma levels of E2 and the expression of the estrogen-dependent trefoil factor 1 (Tff1) gene in testicular tissue. Therefore, our data implicate that in vivo exposure to E2 under specific conditions leads to the premature capacitation of mouse sperm in epididymis with a potential negative impact on the sperm reproductive fitness in the female reproductive tract.

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Sperm capacitation in the human female reproductive tract**Supported by the National Institutes of Health grants HD-15149 and HD-03402.

Fertility and Sterility ◽

10.1016/s0015-0282(16)48396-2 ◽

1985 ◽

Vol 43 (2) ◽

pp. 325-327 ◽

Cited By ~ 38

Author(s):

Hovey Lambert ◽

James W. Overstreet ◽

Patricio Morales ◽

Frederick W. Hanson ◽

Ryuzo Yanagimachi

Keyword(s):

Reproductive Tract ◽

Female Reproductive Tract ◽

National Institutes Of Health ◽

Sperm Capacitation ◽

Human Female

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Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception

Science Translational Medicine ◽

10.1126/scitranslmed.abd5219 ◽

2021 ◽

Vol 13 (606) ◽

pp. eabd5219

Author(s):

Bhawana Shrestha ◽

Alison Schaefer ◽

Yong Zhu ◽

Jamal Saada ◽

Timothy M. Jacobs ◽

...

Keyword(s):

Biomedical Applications ◽

Reproductive Tract ◽

Human Sperm ◽

Female Reproductive Tract ◽

Infertile Woman ◽

Igg Antibodies ◽

Contraceptive Methods ◽

Sperm Binding ◽

Polyvalent Immunoglobulins ◽

Unique Surface

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.

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Is there a role for the endocannabinoid system in the modulation of sperm capacitation within the female reproductive tract?

Fertility and Sterility ◽

10.1016/j.fertnstert.2008.07.1676 ◽

2008 ◽

Vol 90 ◽

pp. S323-S324 ◽

Cited By ~ 1

Author(s):

R. Talevi ◽

L. Ricchiari ◽

V. Barbato ◽

A. Samo ◽

S. De Lorio ◽

...

Keyword(s):

Reproductive Tract ◽

Endocannabinoid System ◽

Female Reproductive Tract ◽

Sperm Capacitation

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Role of spermine in mammalian sperm capacitation and acrosome reaction

Biochemical Journal ◽

10.1042/bj2780025 ◽

1991 ◽

Vol 278 (1) ◽

pp. 25-28 ◽

Cited By ~ 21

Author(s):

S Rubinstein ◽

H Breitbart

Keyword(s):

Binding Sites ◽

Acrosome Reaction ◽

Reproductive Tract ◽

Female Reproductive Tract ◽

Sperm Capacitation ◽

Amino Groups ◽

Binding Properties ◽

Mammalian Sperm ◽

Energy Dependent

The binding properties of seminal polyamines to ram spermatozoa and their possible role in sperm capacitation and the acrosome reaction were studied. Binding and release of [14C]spermine from ram spermatozoa occurred at a rate faster than in somatic cells and were not energy-dependent. Release of bound spermine was further facilitated by heparin, a constituent of the female reproductive tract which was reported to induce capacitation and the acrosome reaction. High- and low-affinity polyamine-binding sites were identified, of which the high-affinity site was specific to polyamines with three or more amino groups. We also found that spermine inhibited the acrosome reaction and propose that it is the major seminal decapacitating factor. Since precise timing of capacitation and the acrosome reaction are critical for successful fertilization, it is suggested that the role of seminal spermine is to prevent premature capacitation and the acrosome reaction.

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