Email to a friend
find gene that spurs development of the epididymis
Life Sciences Editor
photo to enlarge
by L. Brian Stauffer
biosciences professor Humphrey
Hung-Chang Yao and his graduate student, Denise
Archambeault. The research team discovered a mutant
mouse embryo that led them to a gene essential
to epididymal coiling.
CHAMPAIGN, Ill. —
Human sperm cells travel up to 6 meters in their transit from testes
to penis, and most of that journey occurs in the epididymis, a tightly
coiled tube that primes the cells for their ultimate task: fertilization.
In a paper released this week in the Proceedings of the National Academy
of Sciences, researchers at the University of Illinois report that they
have discovered a gene – and related mechanism – essential
to the embryonic development of the epididymis.
The findings are the result of a serendipitous discovery, said professor
of veterinary biosciences Humphrey Hung-Chang Yao. His graduate student, Jessica Tomaszewski,
was examining the testes of mouse embryos when she noticed something
odd: In one specimen the normally convoluted coil of the epididymis
was instead a stunted, straight tube.
The lack of coiling had serious implications for the fertility of the
mouse, Yao said.
“If you take sperm directly from the testis and put it into the
female reproductive tract, it won’t swim. It won’t be able
to fertilize the egg,” he said. Going through the epididymis changes
the biochemical properties of the sperm and helps it develop the energy-generating
machinery that allows it to swim. “So without this structure,
under normal circumstances a male cannot be fertile.”
The researchers first thought that the abnormality was due to a lack
of the male hormone, testosterone. Decades of research had shown that
the development and maintenance of male reproductive structures depend
on an increase in testosterone levels that begins in the latter half
of the life of an embryo.
But all the normal indicators of adequate testosterone levels (its production
and other physiological characteristics) were present in the mutant
photo to enlarge
courtesy H. Yao
team compared normal (wild type) and mutant embryonic
development of the Wolffian duct (purple duct in
the images) in the mouse. At day 15.5, no notable
differences are visible, but two days later the lack
of coiling in the mutant embryonic epididymis is
obvious. A stunted epididymis may contribute to infertility
Tomaszewski looked at younger mouse embryos from the same parents, to
see how early in their development the abnormality appeared. She found
the earliest evidence of a lack of proper coiling in the epididymis
between days 15.5 and 17.5. (Mouse gestation is about 19 days.)
Before it is formed in the embryo, the epididymis is part of a structure
called the Wolffian duct. When the male mouse embryo is about 13 days
old, the Wolffian duct begins to grow and differentiate into the plumbing
system connecting testes and vas deferens. This normally occurs in males
shortly after testosterone levels begin their increase. But in the embryos
Tomaszewski had found, the epididymis did not follow the standard path,
even though testosterone production was normal.
From his earlier work, Yao knew that the gene for one component of a
growth factor, inhibin beta A, is highly expressed in the part of the
Wolffian duct that eventually becomes the epididymis. He also knew that
expression of this gene increases in response to a rise in testosterone.
Inhibin beta A forms part of a protein, activin, that spurs a cascade
of activity in certain cells.
By staining the cells of the developing epididymis – for inhibin
beta A and for a marker of activin activation – Yao’s team
was able to show that inhibin beta A was spurring activity in the cells
that form the walls of epididymal tube.
Further study showed that a lack of inhibin beta A led to stasis in
these cells. Without it, the cells divided too slowly to adequately
lengthen the tube.
This research adds to the evidence that while testosterone is the master
switch that triggers the development of male reproductive structures,
it doesn’t work alone, Yao said. Other studies had shown that
testosterone works with other “regionally specific” factors
to spur the development of structures such as the prostate gland or
seminal vesicles. Inhibin beta A is the first such factor shown to
contribute to epididymal coiling, he said.
“The identification of inhibin beta A in the development of the
epididymis is important for understanding the basic biology of male
sexual development,” Yao said. “But it also provides new
insight into male infertility.”
Graduate students Avenel Joseph and Denise Archambeault contributed
to this study. The work was supported in part by the National Institutes
The department of veterinary biosciences is in the College
of Veterinary Medicine.
To view or subscribe to the RSS feed for Science News at Illinois, please
go to: http://illinois.edu/lb/rss/608/text.xml.
Editor’s note: To reach Humphrey Hung-Chang Yao , call 217-333-9362;