MALE CONTRACEPTION UPDATE

Summaries of new peer-reviewed publications

Attitudes/Sociological research
A survey of the reproductive health of Australian men over age 40, “challeng[ing] the belief that men are not interested in or concerned about their health. Almost 90% of [these] men… had visited a doctor in the 12 months before interview, and men expressed high levels of concern about developing reproductive health problems…”
The men in Australia Telephone Survey (MATeS) - lessons for all.
de Kretser DM, Cock M, Holden C.
Med J Aust. 2006 Oct 16;185(8):412-3. No abstract available.
PMID: 17137425

Motility targets
“A homology model constructed for SFEC [Sperm Flagellar Energy Carrier AAC4] predicted unique residues at the entrance to the nucleotide binding pocket of SFEC that are absent in other human ADP/ATP carriers, suggesting opportunities for selective drug targeting.”
Compartmentalization of a unique ADP/ATP carrier protein SFEC (Sperm Flagellar Energy Carrier, AAC4) with glycolytic enzymes in the fibrous sheath of the human sperm flagellar principal piece.
Kim YH, Haidl G, Schaefer M, Egner U, Herr JC.
DevBiol. 2006 Oct 10; [Epub ahead of print]
PMID: 17137571

Heat-based approaches
“The aim of this study was to analyze [the] semen quality of men who underwent orchidopexy for unilateral or bilateral cryptorchidism during childhood… The effects induced by cryptorchidism resolved in childhood seem to include a spermatogenic impairment…”
Cryptorchidism and Semen Quality: A TEM and Molecular Study.
Moretti E, Di Cairano G, Capitani S, Scapigliati G, Baccetti B, Collodel G.
J Androl. 2007 Jan-Feb;28(1):194-9. Epub 2006 Sep 20.
PMID: 16988323

Cell adhesion targets
Proposal to use an FSH-mutant conjugated to occludin peptide as a “nanodevice to transiently compromise the blood-testis barrier… without compromising the tight junction-barrier integrity or cell adhesion in epithelia of other organs.”
Targeted and reversible disruption of the blood-testis barrier by an FSH mutant-occludin peptide conjugate.
Wong CH, Mruk DD, Lee WM, Cheng CY.
FASEBJ. 2006 Dec 13; [Epub ahead of print]
PMID: 17167075

“The ES shares features of adherens junctions, tight junctions and focal contacts… We discuss herein the mechanisms that maintain the cross-talk between ES and blood-testis barrier to facilitate cell movement and orientationin the seminiferous epithelium.”
Ectoplasmic specialization: a friend or a foe of spermatogenesis?
Yan HH, Mruk DD, Lee WM, Cheng CY.
Bioessays. 2007Jan;29(1):36-48.
PMID: 17187371

“At the time of germ cell loss from the seminiferous epithelium as a result of adjudin-induced AJ restructuring without disrupting the BTB integrity, a significant decline in the steady-state dynamin II protein level was detected. This change was associated with a concomitant increase in the levels of two protein complexes at the BTB, namely occludin/ZO-1 and N-cadherin/beta-catenin… [These data] suggest that dynamin II may assist the 'disengagement' of beta-catenin from ZO-1 during BTB restructuring… permit[ing] the occludin/ZO-1 complexes to maintain the BTB integrity when the cadherin/catenin complexes are dissociated to facilitate germ cell movement.”
Dynamin II interacts with the cadherin- and occludin-based protein complexes at the blood-testis barrier in adult rat testes.
Lie PP, Xia W, Wang CQ, Mruk DD, Yan HH, Wong CH, Lee WM, Cheng CY.
J Endocrinol. 2006 Dec;191(3):571-86.
PMID: 17170215

“This microarray profiling study has identified different target genes belonging to several functional groups [cytokines, proteases, transcription factors and signaling molecules] that may be important for the regulation of junction restructuring during spermatogenesis. Some of these genes highlighted herein merit additional research to delineate their role and involvement in spermatogenesis.”
Unraveling the molecular targets pertinent to junction restructuring events during spermatogenesis using the Adjudin-induced germ cell depletion model.
Xia W, Mruk DD, Lee WM, Cheng CY.
J Endocrinol. Jan 02; [Epub ahead of print]

Endocrinological approaches
As we approach a marketable male hormonal contraceptive product, regulatory bodies will be faced with setting approval criteria for these novel products. The members of the Hormonal Male Contraceptive Summit have taken a step toward establishing such criteria by agreeing upon a set of Phase II and III clinical trial guidelines.
10th Summit Meeting Consensus: Recommendations for Regulatory Approval for Hormonal Male Contraception.
Nieschlag E.
J Androl. 2006 Dec 27; [Epub ahead of print]
PMID: 17192594

Supporting endocrinological research
A review of the “chemistry, mechanism of action, and metabolism of testosterone,” followed by a summary of “the pharmacokinetics, advantages and disadvantages” of the various testosterone formulations currently available.
Drug insight: testosterone preparations.
Srinivas-Shankar U, Wu FC.
Nat Clin Pract Urol. 2006 Dec;3(12):653-65.
PMID: 17149382

“We have shown that the 5΄ upstream sequence of rat 5α-reductase type 1 displays all the features of a CpG island, containing several potential binding sites for the transcription factor Sp1… the requirement for Sp1 in the promoter activity and the bidirectionality has been established… The physiological relevance of this bidirectional promoter activity remains to be determined.”
The promoter of the rat 5alpha-reductase type 1 gene is bidirectional and Sp1-dependent.
Blanchard Y,Seenundun S, Robaire B.
Mol Cell Endocrinol. 2006 Dec 26; [Epub ahead of print]
PMID: 17194527

“We generated a germ cell-specific androgen receptor (AR) knockout mouse (G-AR(-/y)) with normal spermatogenesis… [which suggests] the essential roles of AR during spermatogenesis might come from indirect cell-cell communication in a paracrine fashion.”
Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells.
Tsai MY, Yeh SD, Wang RS, Yeh S, Zhang C, Lin HY, Tzeng CR, Chang C.
Proc Natl Acad Sci USA. 2006 Dec 12;103(50):18975-80. Epub 2006 Dec 1.
PMID: 17142319

Proteomic/genomic supporting research
“19 morphologically distinct segments of the rat epididymis” were microdissected, “subjected to microarray analysis” to characterize RNA. “This current study complements our previous segment-dependent analysis of gene expression in the mouse epididymis… [and] these data provide a powerful resource for the research community in future studies of biological factors that mediate sperm maturation and storage.”
The Rat Epididymal Transcriptome: Comparison of Segmental Gene Expression in the Rat and Mouse Epididymides.
Jelinsky SA, Turner TT, Bang HJ, Finger JN, Solarz MK, Wilson E, Brown EL, Kopf GS, Johnston DS.
Biol Reprod. 2006 Dec 13; [Epub ahead of print]
PMID: 17167166

“We [found] that the methylation status of testicular DNA is highly distinct, displaying eightfold the number of hypomethylated loci relative to somatic tissues… [and] that a contributing factor for these differences is that the methylation state of non-CpG-island DNA is correlated with the regional level of GC content within chromosomes and that this relationship is inverted between the testis and somatic tissues… These special properties of testicular DNA point to a broad, distinct epigenetic state that may be involved in maintaining a unique chromosomal structure in male germ cells.”
A unique configuration of genome-wide DNA methylation patterns in the testis.
Oakes CC, LaSalle S, Smiraglia DJ, Robaire B, Trasler JM.
Proc Natl Acad Sci USA. 2007 Jan 2;104(1):228-33. Epub 2006 Dec 26.
PMID: 17190809

“Transcriptional repression, chromatin remodeling, and an emphasis on posttranscriptional gene regulation preserve the totipotent genome of germ cells through generations… In males, all differentiating germ cells become gametes, yet spermatogonia are still connected by bridges. In mouse Tex14 mutants, bridges do not form and germ cells die during meiosis I, so bridges are important, but why?”
Pathway to totipotency: lessons from germ cells.
Seydoux G, Braun RE.
Cell. 2006 Dec 1;127(5):891-904.
PMID: 17129777

A murine hyaluronidase, Hyalp1, is predominately expressed in the testes and “localized on the plasma membrane of the anterior head” of sperm. “Testicular transcripts of Hyalp1 are detected as early as 6 days postparturition,… suggesting that the gene might also play a role in the developing testes… Hyalp1 likely has a unique function in the adult testis, and redundant overlapping ones with Spam1…”
Hyalp1 in murine sperm function: evidence for unique and overlapping functions with other reproductive hyaluronidases.
Miller KA, Shao M, Martin-Deleon PA.
J Androl. 2007 Jan-Feb;28(1):67-76. Epub 2006 Aug 23.
PMID: 16928892

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New information on MaleContraceptives.org: Adjudin and the 'dry orgasm' pill

MaleContraceptives.org is keeping the public informed about promising new male contraceptive leads. Last month we added new summaries of two leads:

• Adjudin, the novel lonidamine analog which disrupts spermatid-Sertoli cell adhesion and results in sloughing of immature and functionally incomplete spermatozoa,
• and the ‘dry orgasm’ pill, drugs which inhibit the longitudinal contractions of the vasa deferentia and may result in an ejaculate containing no sperm.

Congratulations to Dr. Yan Chang’s group at the Population Council and Dr. Nnaemeka Amobi’s group at Kings College London for all the positive press coverage!

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Feature: Population growth and the Millennium Development Goals

At the turn of the millennium, the United Nations set a series of Millennium Development Goals (MDGs) whose aim is to significantly elevate the standard of living for the world’s poorest residents by 2015. While the MDGs include improving maternal health, reducing child mortality, and promoting gender equality, neither population growth nor the importance of access to family planning is ever mentioned. The United Kingdom’s All Party Parliamentary Group on Population, Development and Reproductive Health decided to investigate the relationship between population growth and achieving the MDGs in a series of hearings held during 2006.

Over the course of six months, the group took expert testimony from the representatives of various United Nations offices, the World Health Organization, the World Bank, the International Monetary Fund, Marie Stopes International, the International Planned Parenthood Federation, Population Action International, distinguished academics from around the world, and others too numerous to mention. Richard Ottoway, the Member of Parliament who vice-chaired the hearings, summarized their findings in December: “No country has ever raised itself out of poverty without stabilising population growth… And the MDGs are going to be difficult or impossible to attain without a levelling out of population growth in developing countries."

This recognition that population growth continues to be of critical importance – for political, economic, environmental and social justice reasons – will surely be a boon to the international family planning community. We hope that the Parliamentary group’s forthcoming report – due to be released later this month – will provide some leverage for better funding and help alleviate donor fatigue.

If you’re looking for grantwriting material or graphics, we recommend the Population Hearings website. There you can peruse the testimony of experts and access the images, slideshows, and statistics they submitted to the Parliamentarians.

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Press: Reuters, BBC, Vancouver Sun

Male Contraception: Discovery Stirring Interest Among Scientists, Drug Developers
UVA press release, 20 December
Members of Dr. John Herr’s laboratory at the University of Virginia Health System report the discovery of a new protein within a sperm’s tail that could prove a target for male contraceptive drugs.

Vasectomy alternative offers reversal hope
Vancouver Sun, 18 December
Interview with Dr. Neil Pollock regarding the Intra Vas Device (IVD). Dr. Pollock hopes to conduct a Canadian trial based on initial sperm count results (available this spring) in the ongoing US IVD trial.

Hormone strategy eyed for male contraceptive
Reuters, 14 December
Short article on results of daily testosterone gel plus quarterly DMPA injections for 6 months in 44 men, based on work at the University of Seattle reported in the Journal of Clinical Endocrinology and Metabolism, November 2006. The combination was effective in dramatically suppressing sperm counts with minimal impact on serum lipids. Discusses the need for studies of long-term effects.

Birth Rate in Developing Countries Impeding MDGs, U.K. Parliamentary Group Says
Kaiser Family Foundation, 11 December
“The high birth rate in developing countries undermines the health of adults and children through an increased risk of death during pregnancy and childbirth, poorer infant nutrition and less chance of receiving education… An approach to decrease the birth rate in developing countries should include… making family planning available.”

Birth rate 'harms poverty goals'
BBC News, 8 December
The original report of the UK’s All Party Parliamentary Group on Population, Development and Reproductive Health’s 2006 Population Hearings findings. Delves into the politics of population and poverty.

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Two andrology positions open at UCSF

From Dr. Paul Turek on the Androlog mailing list:

“Please read below about this new academic opportunity in Men’s Reproductive Health at UCSF. Two junior faculty positions are available for interested individuals finishing fellowship or residency training. This NIH funded training program is brand new and the first of its kind for training junior faculty. It emphasizes mentorship and ‘niche play’ research projects that are key to future academic success in our field. Let me know if you have any interested trainees, as I would be glad to talk with them further.”

The Department of Urology at the University of California, San Francisco, is recruiting for two junior faculty positions with research interests in the field of male reproductive health. Relevant areas of research include steroidogenesis, developmental, germ line or embryonic stem cell biology, genetics of infertility, erectile and sexual dysfunction, sexually transmitted diseases, and genetic and reproductive epidemiology. Applicants will qualify for elite academic training at UCSF under a new NIH K-12 grant (1 K12 HD053943-01). Appointments will be for a minimum of 2 years and require a minimum of 75% time devoted to mentored research and training. Training will include relevant coursework in basic science research techniques, clinical trial design, statistics, bioinformatics, ethics, grant writing and manuscript preparation. A career development plan will be tailored for each candidate with the assistance of established UCSF mentors to insure that scholars develop into highly competitive academic faculty. Applicants should hold an MD degree and have Board certification or be Board eligible in Urology, Obstetrics and Gynecology, Endocrinology or other relevant clinical fields, and must be a US citizen or permanent resident. Email (RE: MRHR in subject line) or send a letter of interest and curriculum vitae to Dr. Turek.

Paul J. Turek, MD
Professor, Endowed Chair in Urologic Medical Education
Program Director, Men's Reproductive Health Research Program
UCSF Department of Urology
1600 Divisadero Street, Room A609
San Francisco, CA 94143-1695, USA
PTurek@urology.ucsf.edu
+1-415-353-7352

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Scholarships for Frontiers in Reproduction (FIR) course

From the American Society for Reproductive Medicine:

“Frontiers in Reproduction (FIR) is offering you a unique opportunity for early career physician-scientist or basic scientist for specialized research and career development training in reproduction research. Full or major scholarship support is available to enable admitted individuals to attend the 2007 FIR: Molecular & Cellular Concepts in Reproduction Research training course. It will be held at the Woods Hole, Massachusetts, MBL campus laboratories in Cape Cod from May 6 - June 16, 2007. FIR is not your usual university lecture or laboratory course! You will meet, learn from, and network with international masters of the science topics. This is a mentored 6-week laboratory and lecture course taught by 30-40 leading investigators from 20-30 different institutions from the U.S. and around the world. The course covers research strategies, including views to future directions, and key technology training with hands-on bench/equipment learning experiences in science areas of the reproductive sciences internationally recognized as important to advancing research in the field.”

An application and additional information is available online, or by contacting the course coordinator at fircoordinator@gmail.com. Enrollment is restricted to 20 trainees for maximum direct mentoring. Application deadline is January 12, 2007.

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Calendar of Events

Late-breaking news: Please note the addition since the last newsletter of the February 19-21 ISSRF conference in New Delhi.

Save the date: Save late September/early October for the 2007 “Future of Male Contraception” conference in Seattle, organized by the NICHD and UW. Details coming soon.

January 10	Deadline for ENDO 07 abstract submission
January 10	Deadline for ISSRF 2007 abstract submission
January 12	Deadline for Frontiers in Reproduction participant application
January 12	Deadline for World Congress on Fertility and Sterility abstract submission
January 15	Deadline for ISSRF 2007 registration
February 19-21	Conference on Recent Advances and Challenges in Reproductive Health & Research, and the 17th Annual Meeting of the Indian Society for the Study of Reproduction and Fertility (ISSRF); New Delhi, India
March 5-8	Society for Endocrinology Annual BES Meeting; Birmingham, UK
March 7-10	Contraceptive Technology 2007 West Coast conference; San Francisco, CA, USA
March 8-11	2nd World Congress on Gender-specific medicine and aging: the endocrine impact; Rome, Italy
March 21-24	22nd Annual European Association of Urology Meeting; Berlin, Germany
March 28-31	Contraceptive Technology 2007 East Coast conference; Washington, DC, USA
April 15-19	1st World Congress for Sexual Health; Sydney, Australia
April 18-21	North American Testis Workshop; Tampa, FL, USA
April 21-24	American Society of Andrology 32nd Annual Conference; Tampa, FL, USA
April 25-27	20a Reunión de la Asociación Latinoamericana de Investigadores en Reprodución Humana; Buenos Aires, Argentina
April 28 - May 2	9th European Congress of Endocrinology; Budapest, Hungary
April 30 - May 5	IFFS 19th World Congress on Fertility and Sterility; Durban, South Africa
May 6 - June 17	Frontiers in Reproduction lab and lecture course for research careers in reproductive biology; Woods Hole, MA, USA
June 2-5	89th Annual Meeting of The Endocrine Society, ENDO 07; Toronto, Canada
July 15-20	Gordon Research Conferences Fertilization and Activation of Development; Plymouth, NH, USA

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Editors

Kirsten Thompson, Director of the Male Contraceptive Coalition (MCC)
Email: Kirsten@MaleContraceptives.org
Phone: +1 (510) 292-1186

Elaine Lissner, Director of the Male Contraception Information Project (MCIP)
Email: Lissner@NewMaleContraception.org
Phone: +1 (415) 863-1859 x107