Summaries of new peer reviewed articles
Review
“[Major] advances in genomic and proteomic research have been instrumental in identifying and characterizing genes and proteins expressed uniquely in the testis or other male reproductive organs, which might become 'druggable' targets for non-hormonal male contraceptive development in the future. Through committed research, advocacy and support, male contraceptives are likely to become a valuable addition to the current choices of family planning.”
New perspectives in non-hormonal male contraception.
Mruk DD.
Trends Endocrinol Metab. 2008 Feb 19 [Epub ahead of print]
PMID: 18291665
Immunological approaches
Female and male mice inoculated with [recombinant mouse Izumo] 6His-mIzumo developed a specific serum antibody and the highest antibody titer lasted at least 6 weeks. The serum anti-6His-mIzumo antibody almost completely blocked mouse sperm-egg fusion in vitro. However, there was no significant reduction in fertility for both male and female mice immunized with 6His-mIzumo compared with control mice.
Investigation of recombinant mouse sperm protein izumo as a potential immunocontraceptive antigen.
Wang DG, Huang TH, Xie QD, An G.
Am J Reprod Immunol. 2008 Mar;59(3):225-34.
PMID: 18275515
“In the present study, various synthetic peptides based upon four sperm proteins, namely Izumo, fertilization antigen-1 (FA-1), YLP(12), and SP56 that are involved in various steps of the fertilization cascade were examined for their immunocontraceptive effect. The synthetic peptides were conjugated to four carrier proteins… Immunization with the peptide vaccines based upon Izumo, which is involved in sperm-egg plasma membrane fusion, caused a significant reduction in fertility. The contraceptive effect was enhanced by immunizing with the peptides based upon other antigens (FA-1, YLP(12), and SP56), resulting in an overall 73.33% reduction in fertility. When the antibodies against the peptides disappeared after >9-10 months from circulation and genital tract, all the animals regained fertility.”
Immunocontraceptive effect of Izumo and enhancement by combination vaccination.
Naz RK.
Mol Reprod Dev. 2008 Feb;75(2):336-44.
PMID: 17676591
“The present study provides evidence that plasmid DNA vaccine in saline solution is efficient at inducing GnRH-I specific IgG immune response in mice… Current doses of DNA needed in humans and larger animals are in the order of milligram amounts and ways to reduce this dose are required to keep the manufacturing costs at a reasonable level.” In order to address these issues, “we designed and engineered a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes.”
Immunisation with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes in saline suppresses rodent fertility.
Khan MA, Ogita K, Ferro VA, Kumasawa K, Tsutsui T, Kimura T.
Vaccine. 2008 Mar 4;26(10):1365-74. Epub 2008 Jan 22.
PMID: 18262690
Epididymal targets
An overview of what is known of the functioning of healthy epididymides. Concludes that “it has been recognized for many years that the epididymis might be a vector for male contraception. Ideally, an epididymal approach to contraception would not involve manipulation of steroid hormones and would not require a cessation of spermatogenesis. Rather, it would inhibit an epididymal function required for the development of a fertile ejaculate.”
De Graaf's Thread: The Human Epididymis.
Turner TT.
J Androl. 2008 Jan 24 [Epub ahead of print]
PMID: 18222912
Novel compounds
“The compound 2-(2''-chloroacetamidobenzyl)-3-(3'-indolyl) quinoline contains indole, and quinoline moieties,” two functional classes which have established anti-fertility effects. Rats fed the compound for 8 weeks had reduced fertility, reproductive organ weight, sperm count, and testosterone levels, and an increase in FSH levels. “Fertility and other effects were regained gradually after cessation of treatment.”
Synthesis and assessment of fertility-regulating potential of 2-(2''-chloroacetamidobenzyl)-3-(3'-indolyl) quinoline in adult rats as a male contraceptive agent.
Bhowal SK, Lala S, Hazra A, Paira P, Banerjee S, Mondal NB, Chakraborty S.
Contraception. 2008 Mar;77(3):214-22. Epub 2008 Jan 30.
PMID: 18279694
“An oral 70% methanolic extract of stem of Dendrophthoe falcata (Loranthaceae) at a dose level of 100 mg/kg wt/day fed to male albino rats for 60 days did not decrease body weight, while the testes and epididymides were significantly reduced… At this dose Leydig cell nuclear area and cytoplasmic area, as well as the cross sectional surface area of Sertoli cells, were significantly reduced (P < 0.001) when compared to controls. The reduced sperm count and motility resulted in 100% negative fertility at 100 mg/kg dose level.” All measured toxic city indices were normal.
Effect of methanolic extract of Dendrophthoe falcata stem on reproductive function of male albino rats.
Gupta RS, Kachhawa JB, Sharma A.
J Herb Pharmacother. 2007;7(2):1-13.
PMID: 18285304
Cell adhesion target supporting research
“[We] propose that the activation of MAPK8 and the redistribution of BMF may be integrally involved in the mechanism by which specific germ cells undergo programmed cell death in response to their detachment from Sertoli cells.”
Phosphorylation of Mitogen Activated Protein Kinase 8 (MAPK8) is Associated with Germ Cell Apoptosis and Redistribution of the BCL2 Modifying Factor (BMF).
Show MD, Hill CM, Anway MD, Wright WW, Zirkin BR.
J Androl. 2008 Jan 24 [Epub ahead of print]
PMID: 18222916
Hepatocyte growth factor (HGF) “decreases the levels of testicular occludin and influences the position of the molecule in the tight junctions as demonstrated by confocal microscopy analysis. In fact in the presence of the factor occludin was mainly localized in the suprabasal region of the tubules whereas in its absence occludin was prevalently localized in the basal region… HGF significantly increases the amount of urokinase type plasmogen activator (uPA) present in the testis, suggesting that HGF regulates the amount of active TGFbeta via uPA levels.”
Hepatocyte growth factor modulates Sertoli-Sertoli tight junction dynamics.
Catizone A, Ricci G, Galdieri M.
J Cell Physiol. 2008 Feb 8 [Epub ahead of print]
PMID: 18265003
“These results show that meiotic progression of spermatocytes is dependent on Sertoli cell-activated mitogen activated protein kinases. In addition, high MPM-2 labeling was not acquired by pachytene spermatocytes cultured alone in Sertoli cell conditioned media, indicating a specific need for cell-cell contact between germ cells and Sertoli cells.”
Meiotic progression of rat spermatocytes requires mitogen-activated protein kinases of Sertoli cells and close contacts between the germ cells and the Sertoli cells.
Godet M, Sabido O, Gilleron J, Durand P.
Dev Biol. 2008 Mar 1;315(1):173-88. Epub 2008 Jan 29.
PMID: 18234180
“Here we review the role of mitogen-activated protein kinases (MAPK) cascades in spermatogenesis and spermatozoa functions.”
Mitogen activated protein kinases (MAPKs) as regulators of spermatogenesis and spermatozoa functions.
Almog T, Naor Z.
Mol Cell Endocrinol. 2008 Jan 30;282(1-2):39-44. Epub 2007 Nov 22.
PMID: 18177996
Gamete binding/fusion targets supporting research
“The purpose of this study was to determine the distribution of surface carbohydrates in human spermatozoa from normal and oligospermic subjects… Triticum vulgaris agglutinin (WGA)-binding sites were found to be decreased on acrosomal domain in spermatozoa from oligospermic individuals, while no changes were observed in the binding sites of Concanavalin ensiformis, Peanut agglutinin and Lens clunaris agglutinin.”
Distribution of N- and O-linked oligosaccharides on surface of spermatozoa from normal and infertile subjects.
Purohit S, Laloraya M, Kumar PG.
Andrologia. 2008 Feb;40(1):7-12.
PMID: 18211295
“[We] report the characterization of an additional chaperone in this location, heat shock protein 1 (chaperonin 10) (HSPE1)… [A] number of molecular chaperones are involved in modification of the sperm surface during capacitation to render these cells functionally competent to engage the process of fertilization.”
Identification of the Molecular Chaperone, Heat Shock Protein 1 (Chaperonin 10), in the Reproductive Tract and in Capacitating Spermatozoa in the Male Mouse.
Walsh A, Whelan D, Bielanowicz A, Skinner B, Aitken RJ, O'Bryan MK, Nixon B.
Biol Reprod. 2008 Feb 14 [Epub ahead of print]
PMID: 18276932
“The expression and localization of the human sperm protein hCAP-18/SOB3 were evaluated in human testis and epididymis… [and was] detected in testis germinal cells (from late spermatogonia to spermatozoa) and in the epididymal epithelium.” The authors propose that when the protein “originates in the testis, it would localize inside the acrosome and would participate in ZP binding. In vitro binding experiments of rec-hCAP-18/SOB3 to ZP are under way to confirm our hypothesis.”
Testicular and epididymal dual origin of hCAP-18/SOB3, a human sperm protein.
Doussau M, Lasserre A, Hammami-Hamza S, Massaad C, Gasc JM, Finaz C.
Fertil Steril. 2008 Feb 5 [Epub ahead of print]
PMID: 18258235
Supporting motility research
“This study has verified the importance of [the Src family kinase pp60 c-src] SRC as a key intermediate kinase in promoting the tyrosine phosphorylation events associated with human sperm capacitation.” However, SRC inhibition alone suppressed capacitation associated tyrosine phosphorylation, but did not suppress hyperactivation.
Investigation of the role of SRC in capacitation associated tyrosine phosphorylation of human spermatozoa.
Mitchell LA, Nixon B, Baker MA, Aitken RJ.
Mol Hum Reprod. 2008 Jan 31 [Epub ahead of print]
PMID: 18245108
Methods
“Laser-capture microdissection (LCM) is a recently developed technique that enables the isolation of individual cell populations from complex tissues… This review will discuss three critical issues that are essential for successful procurement of cells from testicular tissue sections; tissue morphology, capture success, and maintenance of molecular integrity.”
Application of laser-capture microdissection to analysis of gene expression in the testis.
Sluka P, O'Donnell L, McLachlan RI, Stanton PG.
Prog Histochem Cytochem. 2008;42(4):173-201.
PMID: 18243898
