MALE CONTRACEPTION UPDATE

Summaries of new peer-reviewed publications

Attitudes / Sociological research
“Overall, 13.2% of men had UFPN [unmet family planning need]: 8.6% wished to limit childbearing and 4.6% wished to delay it… Uncovering male UFPN may support efforts to develop contraceptive methods for men, or methods that increase male… participation; identify modifiable factors in unplanned pregnancy obscured by studying UFPN in women only; and ultimately reduce unplanned pregnancy by increasing overall contraceptive use.”
Unmet family planning need among US men.
Parker WJ, Patel D.
Contraception. 2007 Aug; 76(2):177-8.
DOI: 10.1016/j.contraception.2007.05.079 

Cell adhesion targets
“Cell adhesion molecules of the immunoglobulin superfamily (e.g., JAM/CAR/nectin) participate in germ cell migration by conferring transient adhesion between Sertoli and germ cells through homophilic and heterophilic interactions. The same molecules also comprise the junctional complexes at the BTB… It is likely that the strategy used by viruses and leukocytes to break through junctional barriers is used by germ cells to open up the inter–Sertoli cell junctions.”
A seamless trespass: germ cell migration across the seminiferous epithelium during spermatogenesis
Wang CQF, Cheng CY.
J Cell Biol. 2007 Aug 13; 178(4):549-556.
DOI: 10.1083/jcb.200704061

Immunological approaches
A test of 4 sperm proteins involved in gamete fusion as immunocontraceptive agents. “These findings indicate for the first time that the immunization with Izumo and other sperm peptides, namely FA-1, YLP(12), and SP56, induces antibodies in [the] serum and genital tract that cause a reversible long-term contraceptive effect in female mice… [The] antibodies against the peptides disappeared after >9-10 months from circulation and [the] genital tract, [and] all the animals regained fertility.”
Immunocontraceptive effect of Izumo and enhancement by combination vaccination.
Naz RK.
Mol Reprod Dev. 2007 Aug 3; [Epub ahead of print]
PMID: 17676591

“Leukocytes turned out to be a principal modulator of the activity of the other inflammatory factors… Cytokines, in turn, seem to be dependent on [bacterial action and leukocytes] in order to be involved in the enhancement of oxidative stress reactions.” They conclude that inflammatory reactions may be “linked to deleterious (to sperm function) oxidative stress which may provoke persistent male infertility.”
Innate immunity is linked with oxidative stress and may lead to male infertility
Fraczeka M, Szumala-Kakolb A, Jedrzejczakc P, Kurpisz M.
J Reprod Immunol. 2007 Jul 24; 75(1):A11.
DOI: 10.1016/j.jri.2007.06.028

Identification and immunological investigation of the mouse homolog of human CD52, a known “pathogenic antigen for immunological infertility… [Mouse] antisera showed sperm-immobilizing activities with complement to mouse sperm. The research indicated mouse CD52 had similar biochemical and immunological properties to human CD52.”
Biochemical property and immunogenicity of mouse male reproductive tract CD52 (mrt-CD52)
Itoa K, Hasegawab A, Komoria S, Koyama K.
J Reprod Immunol. 2007 Jul 24; 75(1):32-39.
DOI:10.1016/j.jri.2007.03.001

“This study supports the concept that a multivalent contraceptive vaccine may be administered to female primates evoking both peripheral (IgG) and mucosal (IgA) responses to each component immunogen following an intramuscular route of inoculation with a mild adjuvant, aluminum hydroxide, approved for human use.”
Immunogenicity of a multi-component recombinant human acrosomal protein vaccine in female Macaca fascicularis.
Kurth BE, Digilio L, Snow P, Bush LA, Wolkowicz M, Shetty J, Mandal A, Hao Z, Reddi PP, Flickinger CJ, Herr JC.
J Reprod Immunol. 2007 Jul 20; [Epub ahead of print]
PMID: 17643494

Gamete binding/fusion targets
Support for the theory that CRISP participates in “the sperm-zona pellucida (ZP) interaction that precedes gamete fusion… The finding that deglycosylated rCRISP1 behaves as the untreated protein while the heat-denatured rCRISP1 associated only with the oolema, indicates that the protein ZP-binding ability resides in the conformation rather than in the glycosydic portion of the molecule.”
A Novel Function for CRISP1 in Rodent Fertilization: Involvement in Sperm-Zona Pellucida Interaction.
Busso D, Cohen DJ, Maldera JA, Dematteis A, Cuasnicu PS.
Biol Reprod. 2007 Aug 1; [Epub ahead of print]
PMID: 17671267

“[These] results provide evidence for the involvement of both epididymal DE/CRISP-1 and testicular Tpx-1/CRISP-2 in gamete fusion suggesting the existence of a functional cooperation between homologue molecules as a mechanism to ensure the success of fertilisation.”
Molecular mechanisms involved in gamete interaction: evidence for the participation of cysteine-rich secretory proteins (CRISP) in sperm-egg fusion.
Da Ros V, Busso D, Cohen DJ, Maldera J, Goldweic N, Cuasnicu PS.
Soc Reprod Fertil Suppl. 2007;65:353-6.
PMID: 17644975

Male mice lacking zona pellucida binding protein 1 (ZPBP1) were sterile, “with abnormal round-headed sperm morphology and no forward sperm motility. Ultrastructural studies demonstrated that absence of ZPBP1 prevents proper acrosome compaction, resulting in acrosome fragmentation and disruption of the Sertoli-spermatid junctions. Males null for ZPBP2 were subfertile, demonstrated aberrant acrosomal membrane invaginations, and produced dysmorphic sperm with reduced ability to penetrate zona pellucida.”
Loss of Zona Pellucida Binding Proteins in the Acrosomal Matrix Disrupts Acrosome Biogenesis and Sperm Morphogenesis.
Lin YN, Roy A, Yan W, Burns KH, Matzuk MM.
Mol Cell Biol. 2007 Jul 30; [Epub ahead of print]
PMID: 17664285

“The correlation of hyperactivation with the zona pellucida-induced acrosome reaction of ZP-bound sperm suggests a mechanistic link between hyperactivation and the physiological acrosome reaction in humans.”
Hyperactivation of capacitated human sperm correlates with the zona pellucida-induced acrosome reaction of zona pellucida-bound sperm.
Liu DY, Liu ML, Clarke GN, Baker HW.
Hum Reprod. 2007 Jul 26; [Epub ahead of print]
PMID: 17656416

Endocrinological approaches
“These data indicate that levonorgestrel butanoate (1.0 mg kg(-1)) in combination with 40 mg of testosterone buciclate was the most effective treatment in suppressing spermatogenesis.”
Effects of levonorgestrel butanoate alone and in combination with testosterone buciclate on spermatogenesis in the bonnet monkey.
Sharma RS, Pal PC, Griffin PD, Waites GM, Rajalakshmi M.
Andrologia. 2007 Aug;39(4):117-23.
PMID: 17683459

Endocrinological supporting research
“Testosterone substitution with intramuscular TU is generally well tolerated. Modifications of androgen action are due to both AR CAG repeats and testosterone levels. Adverse observations are mostly seen in obese patients.”
Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men.
Zitzmann M, Nieschlag E.
J Clin Endocrinol Metab. 2007 Jul 17; [Epub ahead of print]
PMID: 17635942

Vasectomy
“In each country, the labour to provide the vasectomy and follow-up services accounts for the greatest portion of the overall cost… Based on the results presented, more effective methods of vasectomy – including facial interposition (FI), thermal cautery, and thermal cautery combined with FI – are more cost-effective than ligation and excision alone.”
Modelling cost-effectiveness of different vasectomy methods in India, Kenya, and Mexico.
Seamans Y, Harner-Jay CM.
Cost Eff Resour Alloc. 2007 Jul 13;5(1):8 [Epub ahead of print]
PMID: 17629921

“The other contraceptive (reversible) vas deferens surgical techniques have not demonstrated sufficient efficacy to be used outside of the context of clinical trials. However the encouraging results of some of these studies could allow their development in the intermediate term.”
Vasectomy and vas deferens contraceptive surgery: legal and technical aspects [Article in French]
Huyghe E, Blanc A, Nohra J, Khedis M, Labarthe P, Rouge D, Plante P.
Prog Urol. 2007 Jun;17(4):789-93.
PMID: 17633987

Supporting proteomic/genomic research
“NYD-SP12 is a recently identified spermatogenesis-related gene with a pivotal role in human testis development… In the association analysis, we demonstrated significant frequency discrepancy of a synonymous sequence polymorphism among the clinical groups with different sperm traits.”
Rapid Evolution, Genetic Variations, and Functional Association of the Human Spermatogenesis-Related Gene NYD-SP12.
Zhang Q, Zhang F, Chen XH, Wang YQ, Wang WQ, Lin AA, Cavalli-Sforza LL, Jin L, Huo R, Sha JH, Li Z, Su B.
J Mol Evol. 2007 Jul 30; [Epub ahead of print]
PMID: 17665087

“[We] hypothesized that regulated expression and subcellular localization of specific importins may be linked to mammalian gonadal differentiation. We identified distinct developmental and cellular localization patterns for importins beta1, alpha3, alpha4 and RanBP5 (importin beta3)…”
Subcellular distribution of importins correlates with germ cell maturation.
Hogarth CA, Jans DA, Loveland KL.
Dev Dyn. 2007 Aug;236(8):2311-20.
PMID: 17654710

“We identify 24 authentic genes with spermatogenic cell-specific expression, and provide comprehensive information about the genes. Our findings establish a new basis for future investigation into molecular mechanisms underlying male reproduction.”
Integrative characterization of germ cell-specific genes from mouse spermatocyte UniGene library.
Choi E, Lee J, Oh J, Park I, Han C, Yi C, Kim DH, Cho BN, Eddy EM, Cho C.
BMC Genomics. 2007 Jul 28;8(1):256 [Epub ahead of print]
PMID: 17662146

“In this report we show clear evidence for the presence of O-glycans in CD52 preparations immunopurified using the murine S19 monoclonal antibody generated against sperm agglutination antigen-1 (SAGA-1), a male reproductive tract specific form of CD52.”
The Sperm Agglutination Antigen-1 (SAGA-1) Glycoforms of CD52 are O-glycosylated.
Parry S, Wong NK, Easton RL, Panico M, Haslam SM, Morris HR, Anderson P, Klotz KL, Herr JC, Diekman AB, Dell A.
Glycobiology. 2007 Jul 19; [Epub ahead of print]
PMID: 17640971

“[These] data indicate that Gfra1 is expressed dominantly in mouse spermatogonial stem cells and that Gfra1 knockdown leads to their differentiation via the inactivation of RET tyrosine kinase, suggesting an essential role of Gfra1 on spermatogonial stem cell regulation.”
Gfra1 Silencing in Mouse Spermatogonial Stem Cells Results in Their Differentiation via the Inactivation of RET Tyrosine Kinase.
He Z, Jiang J, Hofmann MC, Dym M.
Biol Reprod. 2007 Jul 11; [Epub ahead of print]
PMID: 17625109

“This study provides the first evidence for three novel aldolase isozymes in mouse sperm… Phylogenetic analyses and comparative genomics indicate that the retrogenes and splice variant have remained functional and have been under positive selection for millions of years. Their expression is restricted to the male germline and is tightly regulated at both transcriptional and translational levels. All three isozymes are present only in spermatids and sperm and have distinctive features that may be important for localization in the flagellum and/or altered metabolic regulation.”
Three male germline-specific aldolase A isozymes are generated by alternative splicing and retrotransposition.
Vemuganti SA, Bell TA, Scarlett CO, Parker CE, Pardo-Manuel de Villena F, O'brien DA.
Dev Biol. 2007 Jun 18; [Epub ahead of print]
PMID: 17659271

“We demonstrate that several sperm proteins are degraded after a relatively long period of incubation, and some of these proteins are resynthesised when sperm were incubated under capacitation conditions.”
Protein translation in mammalian sperm.
Gur Y, Breitbart H.
Soc Reprod Fertil Suppl. 2007;65:391-7.
PMID: 17644979

“In the first half of this review we describe the interaction of ADAMs with calmegin and try to elucidate the relationship of these proteins to establish the zona binding ability. In the second half of this review we describe other gene manipulated animals that lead to a defect in sperm-egg fusion.”
Sperm-egg interaction and gene manipulated animals.
Inoue N, Yamaguchi R, Ikawa M, Okabe M.
Soc Reprod Fertil Suppl. 2007;65:363-71.
PMID: 17644977

“Mouse sperm with a knock out of the gene encoding GAPDHS are immotile, which demonstrates that most of the ATP needed for sperm motility is generated by glycolysis. Most of the glycolytic enzymes have been localised to the principal piece and some are tightly associated with the fibrous sheath (FS). However, the nature of the protein-protein interactions involved in assembly and maintenance of FS are known for only a few of the component proteins.”
The scaffold role of the fibrous sheath.
Eddy EM.
Soc Reprod Fertil Suppl. 2007;65:45-62.
PMID: 17644954

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New Male Contraception Quarterly report released

The International Male Contraception Coalition has released the second issue of a quarterly report for policymakers, summarizing the quarter’s most intriguing clinical findings and best policy guidance. The report features another 700 signatures from men and women around the world supporting the development and introduction of new contraceptives for men.

Letters explaining why these men and women care about this issue tell poignant personal stories. The cumulative data from the survey characterizing the market for new male contraceptives will be presented as a poster at the Future of Male Contraception conference in Seattle next month.

This report should be an essential part of every researcher’s and policymaker’s arsenal when arguing for increased or sustained funding. In this era of budget cuts in science and reproductive health, a tool like this is vital to be able to quickly and eloquently respond to the inevitable question, “Do men really want this?”

The Quarterly is under a Creative Commons Attribution license, so it can be freely reproduced and excerpted provided it is attributed to the IMCC.

Read the report:
Male Contraception Quarterly, Number 2

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Gates Foundation hires new reproductive health program director

After going through a reorganization, the Bill & Melinda Gates Foundation has affirmed its commitment to reproductive health. As part of that commitment, the foundation has announced that Monica Kerrigan will join as a Senior Program Officer on the Reproductive Health team.

The foundation has already revitalized work on neglected diseases such as malaria and visceral leishmaniasis, partly through its support of the nonprofit drug company “Institute for OneWorld Health.” It hopes to make a similar impact on reproductive health, with a stated goal of "improving contraceptive methods through the discovery, development, and clinical testing of methods that are more acceptable to potential users, easier to use, more effective, and better suited for use in resource-limited settings."

We hope this means the foundation will be in a position to work together with nonprofits and government agencies to get contraceptives such as RISUG, ultrasound, and the IVD tested and to market, now that Gates is beginning to gather the people-power to focus on this area.

More information about Ms. Kerrigan:
"Monica is an experienced manager of reproductive and maternal health initiatives. In her most recent post, she was a Project Officer focused on Maternal and Child Health with UNICEF in Indonesia. Before that Monica worked as a Senior Technical Advisor for Reproductive Health for USAID, also in Indonesia, where she managed a significant family planning and reproductive health portfolio and facilitated program pick-up by the Indonesian government. From 2000-2002 Monica served as a Contraceptive and Condom Security Advisor with USAID in Washington, D.C. In that capacity, she coordinated activities at the global and country level to ensure contraceptive supply. Previously as Deputy Chief of the USAID’s Communications, Management and Training Division, Monica provided technical and strategic guidance to major communication and behavior change programs which reached countries on a variety of health services, including maternal health and family planning. From 1990-1994 Monica directed the Africa office at the Johns Hopkins University Program for International Education in Reproductive Health and provided guidance to ministries of Health and Education to strengthen clinical training and service delivery. Monica served as a Peace Corps volunteer in a rural primary health care setting in Mali."

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Abstracts of interest from ESHRE 2007, Lyon, France

Abstracts of the 23rd Annual Meeting of the European Society for Human Reproduction and Embryology, Lyon, France, 1–4 July 2007:

“Our results suggest that IL-12, IL-10 and IL-18 affect the proliferation of germ cells and also steroidogenesis. Thus these cytokines could be involved in the regulation of physiological functions of the testis–spermatogenesis, in addition to their immunological effect.”
Interleukin (IL)-12, IL-10 and IL-18 differently regulated mouse tubular cell (germ cells) proliferation and testosterone secretion by Leydig cells
Abu Elhija M, Ganaiem M, Eldar-Geva T, Lunenfeld E, Huleihe M
Human Reprod 22(S1):i215.

“During the passage to the fertilization site, spermatozoa are exposed successively to different glycodelin isoforms, which modulate various aspects of sperm functions important for fertilization. GdC is the latest isoform identified (Chiu et al., 2006)… asialoglycoprotein receptor 2 (ASGPR2) is a potential candidate of GdC receptor on human spermatozoa. ”
Glycodelin-C receptor on human spermatozoa
Tam VCG, Chiu PCN, Koistinen R, Koistinen H, Seppala M, Ho PC, Lee KF, Yeung WSB
Human Reprod 22(S1):i215.

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Funding opportunity: Loan repayment for extramural NICHD contraceptive researchers

“The National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), announces the 2007 Extramural Loan Repayment Program for Contraception and Infertility Researchers (CIR-LRP).

“The CIR-LRP provides for the repayment of up to $35,000 of the principal and interest of the extant educational loans of health professionals conducting contraception and/or infertility research for domestic non-profit or government entities for each year of obligated service. Payments equal to 39 percent of total loan repayments are issued to the Internal Revenue Service on behalf of program participants to offset Federal tax liabilities incurred as a result of participating in the program. The program may also provide reimbursement for state and local tax liabilities.

“Through this announcement, the NIH and NICHD invite qualified health professionals who contractually agree to engage in contraception and/or infertility research for at least two years, and who agree to engage in such research for at least 50 percent of their work schedule (not less than 20 hours per week based on a 40-hour work week), to apply for participation in the NIH Loan Repayment Program for Contraception and Infertility Researchers.

“CIR-LRP applications will be accepted September 1, through December 1, 2007. They must be submitted via the NIH Loan Repayment Website (www.lrp.nih.gov).”

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Calendar of events

Planning to attend a male contraception or andrology-related event that's not listed here? Let us know so we can post it and alert your colleagues to interesting upcoming events.

September 14-16	Florence-Utah International Symposium: Genetics of Male Infertility; Florence, Italy
September 21-23	5th Biennial World Congress on Men's Health and Gender; Vienna, Austria
September 26-29	53rd Annual Meeting of the Canadian Fertility and Andrology Society; Halifax, Nova Scotia, Canada
September 27-28	2nd Future of Male Contraception conference; Seattle, WA, USA
September 30	Deadline for British Andrology Society abstract submission
October 13-17	63rd Annual Meeting of the American Society for Reproductive Medicine; Washington, DC, USA
November 1	Deadline for American Society of Andrology abstract submission
November 3-7	American Public Health Association 2007 Annual Meeting “Politics, Policy & Public Health”; Washington, DC, USA
November 15-16	British Andrology Society Annual Meeting; Ware, Hertfordshire, UK
November 16-18	2nd Japan - ASEAN Men's Health & Aging Conference; Ishikawa, Japan
2008
January 1	Deadline for European Society of Contraception abstract submission
April 12-15	33rd Annual Conference of the American Society of Andrology; Albuquerque, NM, USA
April 30 - May 3	10th Congress of the European Society of Contraception; Prague, Czech Republic
May 3-7	10th European Congress of Endocrinology; Berlin, Germany

 

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Editors

Kirsten Thompson, Director of the Male Contraception Coalition (MCC)
Email: Kirsten@MaleContraceptives.org
Phone: +1 (443) 858-1183

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