Summaries of new peer-reviewed publications
Binding / fusion targets
“Antisera to recombinant human ESP inhibited both oolemmal binding and fusion of human sperm in the hamster/egg penetration assay (HEPA). The results indicate that ESP is a human alloantigen involved in sperm/egg binding and fusion.”
Equatorial Segment Protein (ESP) is a Human Alloantigen Involved in Sperm-Egg Binding and Fusion.
Wolkowicz MJ, Digilio L, Klotz K, Shetty J, Flickinger CJ, Herr JC.
J Androl. 2007 Oct 31; [Epub ahead of print]
PMID: 17978344
Motility target supporting research
Flagellar CrPKD2 (Chlamydomonas reinhardtii PKD2, a protein with the characteristics of PKD2 family members) “increased fourfold during gametogenesis, and several CrPKD2 RNA interference strains showed defects in flagella-dependent mating. These results suggest that the CrPKD2 cation channel is involved in coupling flagellar adhesion at the beginning of mating to the increase in flagellar calcium required for subsequent steps in mating.”
Function and dynamics of PKD2 in Chlamydomonas reinhardtii flagella.
Huang K, Diener DR, Mitchell A, Pazour GJ, Witman GB, Rosenbaum JL.
J Cell Biol. 2007 Nov 5;179(3):501-14.
PMID: 17984324
“Although [extracellular] ATP did not affect acrosomal exocytosis or protein tyrosine phosphorylation in sperm from healthy donors, it significantly altered several motility parameters, with the largest effects manifested in increased curvilinear velocity and percentage hyperactivation.”
Effects of extracellular adenosine 5'-triphosphate on human sperm motility.
Edwards SE, Buffone MG, Knee GR, Rossato M, Bonanni G, Masiero S, Ferasin S, Gerton GL, Moss SB, Williams CJ.
Reprod Sci. 2007 Oct;14(7):655-66.
PMID: 18000227
“Here we show for the first time that in addition to expression in the Sertoli-Sertoli tight junctions in the seminiferous tubules, the approximately 32 kDa murine JAM-A is present in elongated spermatids and in the plasma membrane of the head and flagellum of sperm. Deletion of Jam-A, using the gene trap technology, results in flagellar defects at the ultrastructural level. In Jam-A-deficient mice, which have reduced litter size, both progressive and hyperactived motility are significantly affected (P<0.0001) before and, more severely, after capacitation.”
JAM-A is present in mammalian spermatozoa where it is essential for normal motility.
Shao M, Ghosh A, Cooke VG, Naik UP, Martin-Deleon PA.
Dev Biol. 2007 Oct 23; [Epub ahead of print]
PMID: 18022613
“Carnitine and acetylcarnitine are important for the acquisition of motility and maturation of spermatozoa in the epididymis… We conclude that both Na(+)-dependent and -independent carnitine transporters, [carnitine/organic cation transporters] OCTN2 and OCTN3, mediate the supply of carnitine and acetylcarnitine to epididymal spermatozoa in mice.”
Transport of carnitine and acetylcarnitine by carnitine/organic cation transporter (OCTN) 2 and OCTN3 into epididymal spermatozoa.
Kobayashi D, Tamai I, Sai Y, Yoshida K, Wakayama T, Kido Y, Nezu J, Iseki S, Tsuji A.
Reproduction. 2007 Nov;134(5):651-8.
PMID: 17965255
“The cell immobilizing system proposed, associated with the microspectrofluorimetric analysis supported by videoimaging, is a simple, rapid and useful tool for those studies having the goal of correlating the presence and cellular distribution of ion channels with their functional status and their response to physiologic and/or pharmacological molecules.”
A semi-immobilizing system associated with microspectrofluorimetric and videoimaging analysis for intracytoplasmic calcium measurement in individual viable spermatozoa.
Micera E, Albrizio M, Surdo NC, Zarrilli A.
J Biotechnol. 2008 Jan 1;133(1):90-5. Epub 2007 Sep 25.
PMID: 17964676
“Our results suggest that a significant proportion of men investigated for male infertility may be epididymal protein P34H deficient.”
Epididymal P34H protein deficiency in men evaluated for infertility.
Moskovtsev SI, Jarvi K, Legare; C, Sullivan R, Mullen JB.
Fertil Steril. 2007 Nov;88(5):1455-7. Epub 2007 Apr 16.
PMID: 17434498
Endocrinological approach supporting research
“We show that in mice with a unique hypomorphic androgen mutation, which disrupts the feedback loop governing T synthesis, that genes involved in cholesterol biosynthesis/uptake and steroid biosynthesis are upregulated. We identify LH as the central regulatory molecule that controls both steroidogenesis and Leydig cell cholesterol homeostasis in vivo… We show T-signaling can affect the synthesis of steroids and modulates the expression of genes involved in de novo cholesterol synthesis.”
Hormonal Regulation of Testicular Steroid and Cholesterol Homeostasis.
Eacker SM, Agrawal N, Qian K, Dichek HL, Gong EY, Lee K, Braun RE.
Mol Endocrinol. 2007 Nov 21; [Epub ahead of print]
PMID: 18032697
“In addition to their well-known pathways of action, both [FSH and Testosterone] have recently been recognized to have new signaling routes that are linked to the Ca (2+) ion, including, among others, the regulation of cell proliferation by FSH and the regulation of cell migration by testosterone.”
Diverse FSH and Testosterone Signaling Pathways in the Sertoli Cell.
Loss ES, Jacobus AP, Wassermann GF.
Horm Metab Res. 2007 Nov;39(11):806-12.
PMID: 17992635
Patients’ and clinicians’ experience with an oral formulation of T in hypogonadal men. “The study was performed in 43 centres in Austria and a dosage of oral testosterone undecanoate of 2x80 mg/day was used for three months… average treatment duration was 13.9 +/- 2.2 weeks. Serum testosterone level increased by more than 50% from 8.7 +/- 4.3 nmol/L to 13.2 +/- 6.7 nmol/L (p < 0.001)… There were no significant effects on serum PSA levels.”
Clinical experience with Andriol(R) Testocaps(R)- The first Austrian surveillance study on the treatment of late-onset hypogonadism.
Jungwirth A, Plas E, Geurts P.
Aging Male. 2007 Dec;10(4):183-7.
PMID: 18033627
“It is suggested that FSH- and testosterone-stimulated tPA expression in Sertoli cells may be via PKA and ERK signal transduction… This study further suggests that testosterone-induced tPA activity in the Sertoli cells might be related to the function of blood-testis barrier opening and/or closing.”
Testosterone upregulation of tissue type plasminogen activator expression in Sertoli cells: tPA expression in Sertoli cells.
Guo J, Shi YQ, Yang W, Li YC, Hu ZY, Liu YX.
Endocrine. 2007 Aug;32(1):83-9. Epub 2007 Oct 9.
PMID: 17992606
Retinoic acid receptor approach
Are the effects of retinoids in vitamin A deficient mice “the result of a direct action on germ cells or are [they] indirectly mediated through Sertoli cells”? “In the absence of feeder cells, RA (retinoic acid) directly induces the transition of undifferentiated spermatogonia to differentiating spermatogonia by stimulating Stra8 and Kit gene expression [and] RA dramatically stimulates Stra8 expression in undifferentiated spermatogonia but has a lesser impact in differentiating spermatogonia…”
Expression of Stimulated by Retinoic Acid Gene 8 (Stra8) and Maturation of Murine Gonocytes and Spermatogonia Induced by Retinoic Acid In Vitro.
Zhou Q, Li Y, Nie R, Friel P, Mitchell D, Evanoff RM, Pouchnik D, Banasik B, McCarrey JR, Small C, Griswold MD.
Biol Reprod. 2007 Nov 21; [Epub ahead of print]
PMID: 18032419
Review
Dr. John Amory reviews “the drugs that are known to adversely impact spermatogenesis, and/or sperm function and detail what is known about the mechanisms through which these compounds impair fertility in men.”
Drug effects on spermatogenesis.
Amory JK.
Drugs Today (Barc). 2007 Oct;43(10):717-24.
PMID: 17987224
Proteomic / genomic supporting research
“[These] data suggest that GDNF induces CREB/ATF-1 family member phosphorylation and c-fos transcription via the Ras/ERK1/2 pathway to promote the proliferation of SSC. Unveiling GDNF signaling cascades in SSC has important implications in providing attractive targets for male contraception as well as for the regulation of stem cell renewal Vs. differentiation.”
GDNF Up-regulates c-fos Transcription via the Ras/ERK1/2 Pathway to Promote Mouse Spermatogonial Stem Cell Proliferation.
He Z, Jiang J, Kokkinaki M, Golestaneh N, Hofmann MC, Dym M.
Stem Cells. 2007 Oct 25; [Epub ahead of print]
PMID: 17962702
“[Initial] testis development is normal in Etv5(-/-) mice despite decreased body weight, but spermatogonial stem cell (SSC) loss begins between 4 and 8d of age, indicating that ETV5 has effects beginning in the early neonatal period. Etv5(-/-) mice are infertile even when sperm is produced, indicating that ETV5 loss has other effects besides lack of SSC self-renewal that impair fertility.”
Effects of ETV5 (Ets Variant Gene 5) on Testis and Body Growth, Time Course of Spermatogonial Stem Cell Loss, and Fertility in Mice.
Schlesser HN, Simon L, Hofmann MC, Murphy KM, Murphy T, Hess RA, Cooke PS.
Biol Reprod. 2007 Nov 21; [Epub ahead of print]
PMID: 18032421
“The [ubiquitin-specific protease 26] USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. Further research on this issue is in progress.”
Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility.
Zhang J, Qiu SD, Li SB, Zhou DX, Tian H, Huo YW, Ge L, Zhang QY.
Asian J Androl. 2007 Nov;9(6):809-14.
PMID: 17968467
