Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
Condition: Male Infertility; Testicular Diseases; Urologic and Male Genital Diseases; Lead Poisoning
MeSH terms: Infertility; Infertility, Male; Genital Diseases; Testicular Diseases; Genital Diseases, Male; Poisoning; Lead Poisoning
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Keywords: Lead; Male infertility; Gene expression; Economics, Medical