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R K Naz

Publications and source records attributed to R K Naz.

116 records · Page 7Linked to original sources
PubMedDate not supplied

Human synthetic peptide vaccine for contraception targeting sperm.

A vaccine targeting sperm is an interesting approach to contraception. The acceptability of a sperm antigen for contraceptive vaccine development is contingent upon its sperm-specificity, surface expression for antibody binding, and involvement in fertilization. Sperm-zona pellucida (ZP) binding is a pivotal step and constitutes an attractive site for immunointerception. Using phage display technology, we have identified a novel dodecamer peptide sequence, designated as YLP(12), that is present on sperm, and is involved in ZP binding and sperm capacitation/acrosome reaction in man/mouse. Extensive search in the human and mouse genome sequence databases did not indicate a complete identity with the YLP(12) nucleotide sequence. It is peptide mimetic with sperm receptor carbohydrate mimicking action that is involved in oocyte binding. The sperm-specific YLP(12) sequence is also involved in involuntary immunoinfertility in men, indicating its autoantigenicity, sperm-specificity, and involvement in fertility/infertility in humans. Vaccination of female animals with synthetic YLP(12) peptide causes a long-term reversible contraception by raising a sperm-specific immune response. The contraceptive effect could also be completely reversed voluntarily at any time by immunoneutralization of antibodies using intravaginal administration of the peptide. Thus, the novel synthetic YLP(12) peptide is an attractive candidate for contraceptive vaccine development, and diagnosis and treatment of immunoinfertility in humans.

Acrosome Reaction↗
PubMedDate not supplied

Thymosin alpha 1 levels in human seminal plasma and follicular fluid: implication in germ cell function.

High levels of thymosin alpha 1 (T alpha 1) were detected in human seminal plasma and follicular fluid. In the seminal plasma of 19 males studies, T alpha 1 levels varied from 614 to 2,604 pg/mL (mean +/- SD, 1,682.4 +/- 453.9 pg/mL). There was a correlation between the T alpha 1 levels and the total number of sperm in the ejaculate (r = .18) and seminal volume (r = .26). The infertile males, who had low levels of T alpha 1 also demonstrated fewer sperm, reduced motility, and lower semen volume. In follicular fluid collected from 24 follicles of 10 infertile females, T alpha 1 levels varied from 1,019 to 6,384 pg/mL (mean +/- SD, 3,572.8 +/- 1,599.7 pg/mL), which were higher when compared with the corresponding serum levels (mean +/- SD, 1,666.9 +/- 1,378.9 pg/mL). T alpha 1 levels present in follicular fluids which had "immature" oocytes were lower when compared with follicular fluids which had "intermediate" or "mature" oocytes. The immunoreactive T alpha 1 present in seminal plasma of males and in the follicular fluids of females may be involved in some aspect of germ cell maturation and function. The measurement of T alpha 1 levels may be useful in the diagnosis and treatment of male and female infertility, and also as a novel marker for the assessment of maturity of oocytes required for in vitro fertilization-embryo transfer.

Female↗
PubMedDate not supplied

Increased levels of interleukin-6 in seminal plasma of infertile men.

The presence of various cytokines, namely the tumor necrosis factor (TNF-alpha), interferon (IFN-gamma), and interleukins (IL-1 beta and IL-6), was investigated in seminal plasma of fertile, infertile, and immunoinfertile men using specific immunoradiometric assays. TNF-alpha and IL-1 beta were not detected. IFN-gamma was detected, but the differences between the levels of fertile and infertile/immunoinfertile were not significant (P > 0.05). IL-6 was detected in seminal plasma with significantly higher levels in infertile/immunoinfertile men compared to those of fertile men. IL-6 was also present in sera, and interestingly, the levels in sera were lower than those in seminal plasma. IL-6 levels in seminal plasma correlated significantly with some sperm parameters and penetration rates in the human sperm penetration assay (SPA). These findings suggest that IL-6 is associated with infertility and may be of importance in specific diagnosis and treatment of male infertility.

Adult↗
PubMedDate not supplied

Interleukin-6 enhances the fertilizing capacity of human sperm by increasing capacitation and acrosome reaction.

The effects of human recombinant interleukin-6 (IL-6) on human sperm penetration of zona-free hamster ova (SPA) and human sperm cell capacitation and acrosome reaction were investigated. IL-6 at higher concentrations (60-600 pg/100 microliters) significantly (P < 0.001) increased rather than decreased the human sperm penetration rates in SPA. The effects were specific because immunoadsorption with the specific neutralizing antibody completely abolished the enhancing effects of IL-6. At the same concentrations, IL-6 also significantly enhanced spontaneous as well as calcium ionophore-induced acrosome reaction and release of acrosin from the human sperm cells. There was no effect of IL-6 on percent sperm motility, although it significantly affected various motility characteristics such as velocity, linearity, amplitude of lateral head displacement (ALH), and beat frequency of sperm cells--the motility parameters involved in hyperactivation phenomenon of sperm cells. These results demonstrate for the first time that IL-6 provides a positive signal in enhancing fertilizing capacity of human sperm by increasing capacitation leading to acrosome reaction, and thus it may have clinical applications in the treatment of male infertility in humans.

Acrosin↗
PubMedDate not supplied

Effects of epidermal growth factor on human sperm cell function.

The effects of human recombinant epidermal growth factor (EGF) on the fertilizing capacity of human sperm were investigated. At lower concentrations (0.1-10 nM) EGF did not significantly (P > 0.05) affect human sperm penetration of zona-free hamster oocytes (SPA). At higher concentrations (25-100 nM), EGF significantly (P = 0.01 to < 0.001) decreased the human sperm penetration rates in SPA. At higher concentrations (> or = 25 nM), EGF also significantly inhibited the spontaneous as well as calcium ionophore-induced acrosome reaction and release of acrosin from human sperm. There was no effect of EGF on percent sperm motility, but at higher concentrations (> or = 25 nM) it significantly affected various sperm motility characteristics especially velocity and amplitude of lateral head displacement. EGF was detected by radioimmunoassay as well as radioreceptor assay in seminal plasma of fertile men. However, there were no statistical differences between the levels of EGF or EGF/transforming growth factor (TGF-alpha) in seminal plasma of fertile, infertile, and immunoinfertile men. Also, there was no significant correlation of the EGF or EGF/TGF-alpha levels with total sperm number, sperm motility characteristics, and penetration rates in SPA in these patients. These results indicate that EGF has either no effect or an inhibitory/negative effect on the human sperm cell capacitation and/or acrosome reaction, especially at higher concentrations (> 25 nM).

Acrosin↗
PubMedDate not supplied

Hexokinase present in human sperm is not tyrosine phosphorylated but its antibodies affect fertilizing capacity.

The present study was conducted to investigate the presence of hexokinase in human sperm cell, its subcellular localization, its modulation and role in capacitation/acrosome reaction, and tyrosine kinase activity, if any. These studies were conducted using antibodies (Ab) raised against rat brain hexokinase (type I isozyme) that have significant cross-reaction with various human tissue hexokinases and neutralize the catalytic activity of the enzyme. Hexokinase Ab reacted with acrosomal, mid-piece and tail regions of methanol-fixed (approximately 70-80%) and live (approximately 35-52%) sperm in the indirect immunofluorescence technique (IFT) and the immunobead binding technique (IBT), respectively. Hexokinase Ab specifically recognized a band of 116 kDa on the Western blot of detergent-solubilized human sperm preparation that was different from the 95-kDa phosphotyrosine protein. Hexokinase Ab caused a significant (P < 0.01 to < 0.001) and concentration-dependent inhibition of human sperm penetration of zona-free hamster oocytes in the sperm penetration assay (SPA). These data indicate that the hexokinase of 116-kDa molecular weight is present in acrosomal, mid-piece, and tail regions of human sperm. The sperm hexokinase is a glycoprotein that is different from the 95-kDa phosphotyrosine protein and is not phosphorylated at tyrosine residues; however, its antibodies cause agglutination and a concentration-dependent inhibition of fertilizing capacity of human sperm.

Antibodies↗
PubMedDate not supplied

Presence and modulation of interleukin-12 in seminal plasma of fertile and infertile men.

Interleukin-12 (IL-12) is a unique cytokine that recently has drawn considerable attention because of its immunomodulatory properties and its possible involvement in several normal physiological and pathophysiological processes. In the present study, concentrations of IL-12 were determined, in the seminal plasma of fertile (n = 33), male-factor-infertile (n = 27), and immunoinfertile (n = 14) men, to investigate its role, if any, in male infertility. Levels of IL-12 were expressed both as picograms per milliliter and as picograms per milligram protein. IL-12 was detected in seminal plasma of fertile men as well as in that of infertile men. The levels of IL-12 in seminal plasma of both male-factor and immunoinfertile men were significantly (P < 0.05) different from those of fertile men, when levels were expressed as picograms per milligram protein. When expressed as picograms per milliliter, the levels of IL-12 differed significantly between the immunoinfertile group and the fertile/male-factor-infertile group. There was significant correlation between the IL-12 levels and the total sperm count and percentage of morphologically normal sperm in the semen, whether groups were analyzed together or individually by condition. These findings suggest that IL-12 may have a role in fertility and that its derangement may be involved in male infertility.

Adult↗