Featured Research

from universities, journals, and other organizations

Mutation On Y Chromosome Stops Sperm Production

Date:
December 3, 1999
Source:
Howard Hughes Medical Institute
Summary:
After an arduous search, Howard Hughes Medical Institute (HHMI) investigator David Page has found the first mutation on the Y chromosome that prevents sperm production and thus causes male infertility. The finding, described in the December issue of the journal Nature Genetics, may eventually help in the design of male contraceptives and treatments for infertile males.

After an arduous search, Howard Hughes Medical Institute (HHMI) investigator David Page has found the first mutation on the Y chromosome that prevents sperm production and thus causes male infertility. The finding, described in the December issue of the journal Nature Genetics, may eventually help in the design of male contraceptives and treatments for infertile males.

"It's been very difficult to find the smoking gun—the definitive evidence that any particular gene is the cause of male infertility," said Page, whose laboratory is at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. "Of course this is only one case so we have certainly not solved a public health problem. But at least it's a first instance where we can provide an explanation."

Researchers have uncovered the genetic causes for a flood of diseases as more DNA data have become available. But the study of infertility has lagged. "The very idea that infertility could be genetic seemed not all that logical," said Page. "Most people didn't get beyond the idea of what genetics is—the study of disease passed on in families—and the definition of infertility—the inability to have families."

Genetics and infertility can coexist, however. The impact of an infertility mutation can be hidden, for example, depending on the identity of other genes present in an individual. Thus it is important to see if signs of male infertility, such as a low sperm count, coincide in related individuals such as brothers and uncles.

For now only about 20 percent of cases of male infertility can be traced either to the loss of a large chunk of the male Y chromosome, or to some other large chromosome abnormality, such as the presence of a second X chromosomes in a male. Normal males have an X and a Y chromosome, whereas females have two X chromosomes.

Page wanted to see which gene within one of the large missing Y chromosome chunks was important. He first determined the entire DNA sequence for a region of the Y chromosome that is missing in a number of infertile males. He found that the region contained only two genes, so he set out to test the DNA sequence of the genes in 576 infertile males.

One of the genes, named USP9Y, contained variant DNA sequences in the samples from five of the infertile males. Four of the changes were harmless red herrings—they were also present in a fertile brother or father or caused no change in the final protein product from the gene. But the change in one individual, code-named WHT2780, was not present in the individual's fertile brother, even though the two brothers had inherited the same Y chromosome from their father.

"The mutation must have appeared for the first time in WHT2780, and thus is an excellent candidate for causing his infertility," explained Page.

WHT2780 does not produce any sperm, but he does produce a messy mixture of sperm-precursor cells. Sperm cells normally pass through these precursor stages over a period of 65 days, as they move through the convoluted seminiferous tubules that wind through the testes.

"I expected that these mutations would cause interruptions at discrete points in the 65-day process," said Page. "In a typical infertile male the problem is a reduction in the overall volume of sperm production."

Some tubules appear to function appropriately, while others do not function at all. "It's as if the lights are going out one by one," said Page. "It makes me wonder whether the key to many of the problems will go back to the germ stem cells—the original sperm progenitor cells—whose job it is to keep the tubules populated with sperm-producing cells."

To see if that speculation is a reality, Page needs to determine USP9Y's function and identify more genes that cause male infertility. The latter task will not be easy, as some genes on the Y chromosome come in multiple similar versions that confuse analysis, but Page's job will be made easier by the determination of the complete sequence of the Y chromosome. Page and his colleagues expect to have the finished blueprint for the Y chromosome by the end of the year 2000.

A better understanding of how mutation causes infertility could suggest how to create infertility at will. A drug that antagonizes a gene such as USP9Y has the potential to be a male contraceptive.

Then there is the even more challenging prospect of correcting mutations that cause infertility. "There may be public health jackpots to be found," said Page. "It's going to be a challenge to find them, but they're probably out there."


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "Mutation On Y Chromosome Stops Sperm Production." ScienceDaily. ScienceDaily, 3 December 1999. <www.sciencedaily.com/releases/1999/12/991203081043.htm>.
Howard Hughes Medical Institute. (1999, December 3). Mutation On Y Chromosome Stops Sperm Production. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/1999/12/991203081043.htm
Howard Hughes Medical Institute. "Mutation On Y Chromosome Stops Sperm Production." ScienceDaily. www.sciencedaily.com/releases/1999/12/991203081043.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Uganda on Alert for Ebola but No Confirmed Cases

Uganda on Alert for Ebola but No Confirmed Cases

AFP (July 31, 2014) Uganda's health minister said on Thursday that there are no confirmed cases of Ebola in the country, but that it remained on alert for cases of the deadly virus. Uganda has suffered Ebola outbreaks in the past, most recently in 2012. Duration: 00:59 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins