Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00012480
Status:
COMPLETED
Last Update Posted:
2015-04-15
First Post:
2001-03-09
Brief Title:
Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
Sponsor:
National Institute of Environmental Health Sciences NIEHS
Organization:
National Institute of Environmental Health Sciences NIEHS
Study Overview
Official Title:
Human Sperm Zona Acceptor Environmental Effects
Status:
COMPLETED
Status Verified Date:
2015-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 Leads 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 mechanisms underlying leads 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 ie more than 61 million people in the US 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 causes 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
The American Urological Association and the American Society for Reproductive Medicine report that 15 of couples ie more than 61 million people in the US 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 causes 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None