Summaries of new peer-reviewed publications
Review
A survey of all contraceptive methods available to men, ranging from condoms and vasectomy to emerging methods. “Male contraception research has yielded a number of promising leads over the past 50 years. Yet little is known by the public due to lack of institutional support and funding. This in unfortunate since, apart from condom and vasectomy, there are many male methods which may be safer, more effective and easier to use.”
Male contraception: Past, present and future.
Herdiman J, Nakash A, Beedham T.
J Obstet Gynaecol. 2006 Nov;26(8):721-7.
PMID: 17130015
Cell adhesion targets
Exploration of the molecular causes of infertility in male symplastic spermatid (sys) mice. The authors identify the deletion of a gene on chromosome 14, Fndc3a, as the primary cause of the sys phenotype, in which male mice are infertile due to the “loss of adhesion between spermatids and Sertoli cells occur[ing] at step 8.” They locate the gene product in step 2-10 spermatid acrosomes and in Leydig cells, concluding that the mechanism through which FNDC3A “mediate[s] adhesion between Sertoli cells and round spermatids” is as yet unknown.
FNDC3A is required for adhesion between spermatids and Sertoli cells.
Obholz KL, Akopyan A, Waymire KG, MacGregor GR.
Dev Biol. 2006 Oct 15;298(2):498-513. Epub 2006 Jul 8.
PMID: 16904100
Immunological approaches
A review of the status of the peptide vaccines being developed against conception, including 8 sperm peptide targets, LDH-C4 among them.
Peptide vaccines against cancer, infectious diseases, and conception.
Naz RK, Dabir P.
Front Biosci. 2007 Jan 1;12:1833-44.
PMID: 17127424
Motility targets
“Ion channel blockers remain attractive model contraceptive drugs because of their ability to modulate cholesterol levels [in sperm membranes]. However, the large number of sperm ion channel variants shared with other cell types make ion channels less attractive targets… than a few years ago. In this review, the genetics, structure and function of voltage-dependent calcium channels and related CatSper molecules will be discussed…”
Voltage-dependent calcium channels in mammalian spermatozoa revisited.
Benoff S, Chu CC, Marmar JL, Sokol RZ, Goodwin LO, Hurley IR.
Front Biosci. 2007 Jan 1;12:1420-49.
PMID: 17127392
Supporting motility research
Sperm tail protein NYD-SP28 “is expressed in cytoplasm of spermatogenic cells… [and] NYD-SP28 immunoreactivity was detected in [the] entire sperm tail.” The protein, which contains “a cluster of phosphorylation sites, N-glycosylation sites and N-myristoylation sites… [is] post-translationally modified during sperm capacitation.”
Cloning and characterization of a novel sperm tail protein, NYD-SP28.
Zheng Y, Zhang J, Wang L, Zhou Z, Xu M, Li J, Sha JH.
Int J Mol Med. 2006 Dec;18(6):1119-25.
PMID: 17089017
High mitochondrial membrane potential in sperm is correlated with “normal morphology, high motility values, and calcium ionophore-induced acrosome reaction, suggesting the importance of mitochondrial functionality for fertilizing capacity of human spermatozoa.”
The functionality of mitochondria differentiates human spermatozoa with high and low fertilizing capability.
Gallon F, Marchetti C, Jouy N, Marchetti P.
Fertil Steril. 2006 Nov;86(5):1526-30. Epub 2006 Sep 25.
PMID: 16996512
Supporting endocrinological research
“… [T]he predominance of FSH isoforms bearing fully processed oligosaccharides in circulation may contribute to the development and maintenance of seminiferous epithelium function in men… Although the physiological significance of a hormone existing as glycosylation variants has not been clarified yet, it has been postulated that signal transduction systems can be differentially activated by specific carbohydrate structures present in the hormone.”
Carbohydrate complexity and proportions of serum FSH isoforms in the male: Lectin-based studies.
Campo S, Ambao V, Creus S, Gottlieb S, Fernandez Vera G, Benencia H, Bergada C.
Mol Cell Endocrinol. 2007 Jan 2;260-262:197-204. Epub 2006 Nov 2.
PMID: 17084021
“Using a Cre-loxP conditional knockout strategy, we generated a tissue-selective knockout mouse with the AR gene deleted in testis peritubular myoid cells (PM-AR(-/y)).” With the exception of smaller testes, these mice were phenotypically identical to wild type; they have comparable serum T concentrations and normal fertility. However, PM-AR(-/y) mice had oligozoospermia in the epididymis and decreased total germ cell number. These mice had “defects in the expression of Sertoli cells’ functional marker genes.”
Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells.
Zhang C, Yeh S, Chen YT, Wu CC, Chuang KH, Lin HY, Wang RS, Chang YJ, Mendis-Handagama C, Hu L, Lardy H, Chang C.
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17718-23. Epub 2006 Nov 9.
PMID: 17095600
“hCG and hCG-derived molecules of non-placental origin have recently been substantiated in… the human testis and the human prostate… hCGα is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGα and hCGβ in male and female fertility.”
Human chorionic gonadotropin (hCG) in the male reproductive tract.
Berger P, Gruschwitz M, Spoettl G, Dirnhofer S, Madersbacher S, Gerth R, Merz WE, Plas E, Sampson N.
Mol Cell Endocrinol. 2007 Jan 2;260-262:190-6. Epub 2006 Nov 9.
PMID: 17097221
“A specific haplotype (AGATA) in the estrogen receptor alpha (ER1) gene was recently described as a new risk factor for cryptorchidism in the Japanese population… We confirm that SNP12 is the tag SNP for the AGATA haplotype also in Caucasians. However,… we found a protective effect for ESR1 SNP12 on cryptorchidism in the Italian population. No association between SNP12 and severe spermatogenic disturbances was observed.”
Molecular analysis of estrogen receptor alpha gene AGATA haplotype and SNP12 in European populations: potential protective effect for cryptorchidism and lack of association with male infertility.
Galan JJ, Guarducci E, Nuti F, Gonzalez A, Ruiz M, Ruiz A, Krausz C.
Hum Reprod. 2006 Nov 10; [Epub ahead of print]
PMID: 17099213
Proteomic/genomic supporting research
Identification and functional categorization of the 381 proteins of the Drosophila melanogaster sperm proteome. Gene ontology functional groups included proteolysis (3%), DNA/RNA binding (6%), cytoskeletal and central metabolism (9% each), energetics (12%), miscellaneous functions (13%) and catalysis (13%). The remaining 31% of the proteins have, as yet, no molecular function predictions.
Genomic and functional evolution of the Drosophila melanogaster sperm proteome.
Dorus S, Busby SA, Gerike U, Shabanowitz J, Hunt DF, Karr TL.
Nat Genet. 2006 Dec;38(12):1440-5. Epub 2006 Nov 12.
PMID: 17099714
Primarily a methodological report of the search for “specific genes related to the meiosis of germ cells during spermatogenesis in the rat testis.”
Meiosis related gene expression in rat spermatogenesis. [Chinese]
Liu DY, Wu YW.
Zhonghua Nan Ke Xue. 2006 Oct;12(10):883-7.
PMID: 17121015
“In humans, all three [BOULE] isoforms are exclusively expressed in the testes in a relative proportion of 80:220:1 for B1, B2 and B3, respectively… Alteration of the B1/B2 and B1/B3 transcript ratios was correlated with reduced meiotic capacity of spermatocytes to produce round spermatids as assessed by flow cytometry.”
Association of three isoforms of the meiotic BOULE gene with spermatogenic failure in infertile men.
Kostova E, Yeung CH, Luetjens CM, Brune M, Nieschlag E, Gromoll J.
Mol Hum Reprod. 2006 Nov 17; [Epub ahead of print]
PMID: 17114206
“By analysis of a large number of subjects…, we showed the first genetic evidence that [single nucleotide polymorphism mutations in three of the typical folate metabolism enzymes] MTHFR C677T, MS A2756G and MTRR A66G genotypes were independently associated with male infertility.”
Mutations in the testis-specific NALP14 gene in men suffering from spermatogenic failure.
Westerveld GH, Korver CM, van Pelt AM, Leschot NJ, van der Veen F, Repping S, Lombardi MP.
Hum Reprod. 2006 Dec;21(12):3178-84. Epub 2006 Aug 24.
PMID: 16931801
“NALP14 was, as are the three other genes in 11p15, exclusively expressed in the testis. Within the testis, the NALP14 protein was mainly expressed in A dark spermatogonia, mid and late spermatocytes and spermatids… Our data suggest that NALP14 has a function in spermatogenesis and that mutation in this gene might cause spermatogenic failure.”
Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility.
Lee HC, Jeong YM, Lee SH, Cha KY, Song SH, Kim NK, Lee KW, Lee S.
Hum Reprod. 2006 Dec;21(12):3162-70. Epub 2006 Jul 22.
PMID: 16861746
Based on the genotyping of 167 idiopathically infertile men, data indicate that a single nucleotide polymorphism at the KIT tyrosine kinase receptor “may be involved in a low sperm count trait in humans.”
Association of genetic markers within the KIT and KITLG genes with human male infertility.
Galan JJ, De Felici M, Buch B, Rivero MC, Segura A, Royo JL, Cruz N, Real LM, Ruiz A.
Hum Reprod. 2006 Dec;21(12):3185-92. Epub 2006 Aug 11.
PMID: 16905672
“Haspin is a unique protein kinase expressed predominately in haploid male germ cells… The transcript unit of Gsg2 contains features of germ cell-specific genes, including the lack of introns and a GC-rich DNA sequence. Further studies on the regulation of Gsg2 will help detail the transcriptional control of germ cells and their evolutionary history, such as the diversification of the genes by retrotransposons.”
The 193-Base Pair Gsg2 (Haspin) Promoter Region Regulates Germ Cell-Specific Expression Bidirectionally and Synchronously.
Tokuhiro K, Miyagawa Y, Yamada S, Hirose M, Ohta H, Nishimune Y, Tanaka H.
Biol Reprod. 2006 Nov 22; [Epub ahead of print]
PMID: 17123944
