Our data indicate that environmental exposure to the heavy metal lead are more widespread than currently appreciated and that such exposures are associated with the production of human male subfertility. Lead's effects are observed in male partners of infertile couples attending an IVF clinical, in men acting as semen donors in an artificial insemination program and in men representative of the general public. Our goal is to identify the mechanism(s) underlying lead's anti-fertility action.

Condition
Male Infertility Testicular Diseases Urologic and Male Genital Diseases Lead Poisoning

Further Study Details: 

Expected Total Enrollment:  400

Our goal is to understand how environmental and occupational exposures to heavy and transition metal ions injure the human male reproductive tract.

The American Urological Association and the American Society for Reproductive Medicine report that ~15% of couples (i.e., more than 6.1 million people in the U.S.) experience infertility at some time. The male is responsible for infertility of 20% of these couples and contributes to the infertility of another 30-40%. However, the cause(s) of male infertility in many cases is unknown. Our data suggest that lead exposures (in the air, in food and in drinking water) underlie a significant fraction of "unexplained" male infertility. We found that blood and seminal plasma lead levels were elevated in 22% of normospermic males from couples seeking infertility treatment, in 29% of semen donors participating in an artificial insemination program and in 23% of unselected semen donors answering an advertisement for research participation. These elevated lead levels were associated with decreased sperm fertility potential in IVF, in artificial insemination and in pregnancy by coitus. The negative effects of lead on sperm function was correlated with expression of specific forms of sperm ion channels (metal binding proteins that allow lead to enter cells), suggesting that such proteins serve as markers for susceptibility or resistance to the reproductive toxic effects of lead. Further, in cases in which human male lead levels changed markedly over time, there were corresponding changes in sperm ion channel, sperm function and sperm fertility potential. These changes were linked to changes in calcium modulated processes in human testis biopsies obtained from infertility patients and could be mimicked in testes of rats experimentally fed lead.

In the current study, we plan to identify changes in gene expression important to the production of the infertile state by comparing the genes expressed in the testis of control and lead exposed rats which are resistant or susceptible to lead. These findings will help to explain how lead exposure kill cells within the testis. We will then determine whether the same changes occur in human testis biopsies and ejaculated sperm from infertile males with high body burdens of lead. The expected outcome of this study is the identification of a possible mechanism explaining male infertility associated with low sperm counts or idiopathic male infertility, tools for diagnosis of male infertility and the hope for rationale treatment.

Ages Eligible for Study:  21 Years   -   55 Years,  Genders Eligible for Study:  Male

Accepts Healthy Volunteers

Criteria

• Otherwise healthy men seeking fertility evaluation, without history of urologic infections or varicocele.
• Non-smokers.
• Occupationally exposed to lead or not exposed to lead.
• Otherwise healthy men undergoing testis biopsy for clinical assessment of spermatogenesis or for sperm retrieval prior to an attempt at assisted reproduction.
• Otherwise healthy men providing semen specimens for clinical analysis prior to an attempt at assisted reproduction.

Susan H Benoff, PhD      516-562-1121    sbenoff@nshs.edu
Colleen Millan, MA      516-562-4038    cmillan@nshs.edu

California
      University of Southern California Women's and Children's Hospital, Los Angeles,  California,  90033,  United States; Not yet recruiting
New York
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
Pennsylvania
      Copper Hospital and Fertility Testing Laboratory and Sperm Bank, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting

Study chairs or principal investigators

Susan H Benoff, PhD,  Principal Investigator,  North Shore University Hospital   

Study ID Numbers:  6100-CP-001
Record last reviewed:  September 2002
Last Updated:  October 13, 2004
Record first received:  March 9, 2001
ClinicalTrials.gov Identifier:  NCT00012480
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08