Why Men Have Infertility

Findings may yield methods for improving fertility as well as developing male contraceptives.

For 40 percent of the estimated six million American couples battling infertility, the problem lies with the man. But help may be on the way.

New research in mice by scientists at Rockefeller University and the Population Council sheds light on the causes behind male infertility. The findings, reported in the March issue of Developmental Cell, also include potential targets for developing a reversible male contraceptive.

"The sperm from these mice have problems similar to many defects seen in human sperm that contribute to infertility," says Hermann Steller, Ph.D., head of the Strang Laboratory of Apoptosis and Cancer Biology at Rockefeller. "We have found an event in the maturation of sperm that is extremely sensitive, and thus would be a good target for both improving fertility and quality of sperm for men who are infertile, and for the inhibition of fertility using a male contraceptive pill."

Led by first author Holger Kissel, Ph.D., a postdoctoral researcher in Steller's laboratory, the scientists created a mouse missing a gene called Septin 4; male mice that lack this gene are sterile. While these mice produce the same volume and number of sperm as normal mice, the sperm from the mutant mice is unable to fertilize eggs. The sperm has several defects, including severely bent tails and large droplets of cytoplasm at the area of the cell that surrounds the nucleus. These defects would not normally appear in fertile sperm. The appearance of the mutant mouse sperm is very similar to a human condition known as "droplet sperm."

"The majority of sperm that even a fertile man makes appears abnormal," says Kissel. "The sperm defects we are seeing in the mutant mice are probably an enhanced phenomenon that occurs in normal, healthy mice as well."

This research follows previous work by Steller's lab showing that caspases, known as death enzymes, are needed by fruit flies to make healthy sperm. Instead of killing the cell, as would normally occur, the caspases remove excess cytoplasm from sperm, helping to give them their nice streamlined shape. The new data indicates that the same events occur in mammalian sperm.

"Caspases are needed for the elimination of the majority of the cytoplasm and organelles to make mature sperm," says Steller. "Rather than having death of the whole cell, there is death of only part of the cell. This is clear evidence that this process is conserved from fruit flies to mammals."

The Septin 4 gene, which is missing in the mice with defective sperm, makes both the Septin 4 protein and a protein called ARTS. This second protein is important for activating the death enzymes. The Septin 4 protein, part of a family of proteins first discovered in yeast, is important for making large cytoplasmic scaffolds, similar to construction scaffolding, in cells where proteins can assemble. The scaffolds provide a framework in the cell that helps to compartmentalize different proteins in the cell.

"The Septin 4 protein is normally found in a structure called the annulus in the sperm," says Steller. "The annulus was predicted to be a way to make different compartments in the sperm, and the mutant mice completely lack an annulus. If you normally have to keep all of the proteins in the right compartment, messing that up leads to a number of problems with the sperm, including bent tails and an inability to swim."

Co-author Gary Hunnicutt, Ph.D., the senior collaborative scientist at the Population Council, studies surface compartmentalization and function of sperm.


"Sperm, unlike other cells in the body, must respond and react to a host of different environments in both the male and female reproductive tracts," says Hunnicutt. "Yet they do this without making any new proteins. Instead, they appear to change their functions by rearranging the molecules on their surfaces. The annulus has been thought to act as a gatekeeper that separates two areas of the sperm tail. Studying sperm from mice lacking Septin 4 allows us to finally ask if this is really the case, and the findings will advance our understanding of how sperm become cells capable of fertilization."

Research on the roles of both the ARTS and Septin 4 proteins in sperm maturation may further our understanding of male infertility and potentially improve the fertility and quality of sperm in infertile men. Also, these proteins are attractive targets for male contraceptive drugs, because while the sperm are still produced in the mutant mice, they are unable to fertilize an egg.

"There are not many mutations that cause complete sterility without affecting the anatomy of the testis, as with our mouse," says Kissel. "The Septin 4 and ARTS proteins are great targets because interfering with them could accomplish inhibition of fertility without any negative side effects."

"This is a really great starting point," says Steller. "We were originally interested in the cell death aspects of these proteins, but the mouse has opened up many other nice opportunities-including insights into human sterility-that we are currently pursuing." PregnancyAndBaby.com

Tags: men mice

recommended for you


andyqif November 13, 2014
锘縲herever Tara decided to go as a child where most of the class of each Tara in addition to Kaleb nonetheless get. Their very own some other child, Ethan, appeared to be baptized now there half a dozen a long time ago.

Many people named Rev. Gordon Druggett to help timetable the wedding, nevertheless Kaleb has been astonished to see their small children couldn't become baptized in the religious organization because they don't have a home in Area Brook, they don't really see a place of worship sufficient, and so they moves to the one out of Pasadena if he or she need their young children baptized.

Which will injured the bride and groom. They assert they felt deserted via the just cathedral on the list of i went to. They don't know the folks in the Anglican chapel throughout Pasadena.

Tara what food was in rips soon after receiving the news they wouldn't have the capacity to look at the Playground Generate community center to have the girl's children baptized.

Considering informing his or her story for native radio Tuesday day time, Kaleb reported the actual religious organization offers agreed to explore possibly baptizing the family.

"He definitely wounded us, where to be a serve individuals, consequently we have no real interest in time for that will chapel again,In . Gardner mentioned. "We've lost just about all religion for the reason that chapel.In

Currently plan is to have ceremony along at the Solution Armed forces Citadel around Cranny Stream. Kaleb is probably the Answer Military services, when their partner is definitely Anglican.

Even though the Gardner relatives are certainly not common churchgoers, Kaleb stated they certainly keep Melinda principles.

"We you should not pay a visit to religious weekly," he was quoted saying. "I might possibly not have went to community center since continue X-mas, doesn't imply since we don't visit church doesn't mean he has got the ability to guitar all of us from your religious.

"My partner and so i possess background in this community center. Even if we're not presently there every Sunday, doesn't suggest anything at all. Once we showed each of our religious beliefs it had become normally from St. Michael's. Now, an excellent instant must i action foot or so in this particular church."

Druggett declined comment declaring it was a personalized as well as pastoral subject and he would not statement. Right Rev. Percy Coffin, bishop of the diocese associated with european Newfoundland, ended up being out of town and may quit gotten to intended for comment.閿樼笅asadena Home team Opry on Kyle Chapman Annex

Looking at their home that individual possesses at least one

<a href=http://rhand.org.tt/Uploads/nike/nike18283.html>nike air max plus 2013 review</a>
<a href=http://www.vakantieplaats.nl/application/language/template2.php?moncler-down-jacket-women-jacket-black-1708-p-332.html>Moncler Down Jacket Women Jacket black 1708 Lage Prijs Verkoop Winkel 2014</a>
<a href=http://rhand.org.tt/Uploads/nike/nike22721.html>nike free trainer 5.0 all black</a>
<a href=http://www.www.vakantieplaats.nl/application/language/template.php?2014-moncler-mannen-c-40.html>2014 Moncler mannen</a>
<a href=http://rhand.org.tt/Uploads/nike/nike16901.html>nike performance air max fusion 2</a>
carpinteyrofid November 04, 2014
锘縤ne to mention police officers with regard to "reported possibilities deceptive activity" through Margaret Backus, Devices Director in addition to Nathaniel Mountain, Asst . Archives Home. This report states that, . (just click for more)閿樼笉ick Steves appreciated Denver colorado Springs

However the documented voyager declared that "Grand <a href=http://www.donnajblack.com/nike.php?nike-free-40-v2women-moon-blue-p-557.html>Nike Free 4.0 V2Women Moon Blue</a>Jct attraction is restricted for its pleasant Significant Block," Rick Steves loved your ex certain "stately" Denver Comes not to mention Colorado's medicinal marijuana centers' "happy pharmacy fashion eco-friendly c<a href=http://www.donnajblack.com/nike.php?nike-air-max-90-em-men-laser-blue-p-840.html>Nike Air Max 90 EM Men Laser Blue</a>rosses" he published for their website. (Steves was a student in township to express go tips together with connection when using the regional open telly followers, as a part of a national expedition. Find your review in this article.)

Palatial by means of conquer standards Victorian homes line wide pavements, knowing how the days should the neighborhood prospecting upper class described Denver co Spgs substantial world though nurturing notable very poor. Tasteful in addition to elegant for just a Nuts Western side city, nonetheless believes individually trendy along with elegant currently. And not much too formal. In doing my afternoon address within the incredible Neo Romanesque Hide Church on the Co University college campus, filled with lots of travelers my very own host reminded everyone, inside Denver colorado way to wear some clean skinny jeans. with regard to Bumpy Mountain PBS plus the regional community broadcast station (Common 88.Seven KCME FM), I was set up on on the list of finest hotels you can imagine: your backyard of your Gods Club Resort. This portion of the 480 acre residence directed at the community during perpetuity to acquire the particular assurance this <a href=http://www.donnajblack.com/nike.php?nike-air-9087-hyp-women-orange-white-p-1087.html>Nike Air 90&87 HYP Women Orange White</a>alcoholic drinks wouldn't always be provided, distributed, or simply ingested around the real estate. Our home ignored towering crimson dirt which will sparkle each day sunshine together with prompted weary creators of Camels. Running in my bathrobe recent grazing deer plus courageous rabbits towards the backyard pool, I started my past daytime in the mountains through taking a soak plus gazing from the water at the glowing pink camels french kissing in the foot or so from the Rockies.

Amusingly this is, subject to if you are any upline KCME's Brenda Bratton was feeling left out from the unique submit, posting a quick opinion concerning the absence of credit (which has been in the future adjusted).

"It could have been good<a href=http://www.donnajblack.com/nike.php?nike-air-max-1-men-nike-air-max-1-c-73_75.html>Men Nike Air Max 1</a> to get w

<a href=http://www.donnajblack.com/nike.php?adidas-climacool-fresh-ride-c-84.html>adidas ClimaCool Fresh Ride</a>
<a href=http://www.donnajblack.com/nike.php?nike-sb-paul-7-low-prm-beige-red-p-41.html>Nike SB Paul 7 Low PRM Beige Red</a>
<a href=http://www.donnajblack.com/nike.php?nike-air-max-2012-c-49.html>Nike Air Max 2012</a>
<a href=http://www.donnajblack.com/nike.php?nike-air-max-tr-180-leather-men-women-lsu-p-760.html>Nike Air Max TR 180 Leather Men Women LSU</a>
<a href=http://www.donnajblack.com/nike.php?nike-free-run-4-men-carbon-red-p-387.html>Nike Free Run 4 Men Carbon Red</a>