“Eight times out of 10, conventional genetic testing doesn’t reveal
a chromosomal problem, so the cause is considered idiopathic or
unknown,” Dr. Yatsenko said. “This study is among the first to describe
specific gene mutations on the X chromosome that contribute to
azoospermia and male infertility.”
First, the research team scanned the genomes of 15 men with
azoospermia and found a deletion in part of the DNA coding of the
testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit
from their mothers. The alteration caused meiotic arrest, meaning the
precursor cells could not properly undergo meiosis, the cell division
process that produces daughter cells with half the parental chromosomes
for reproduction.
Then, they found similar TEX11 gene mutations and meiotic arrest in
two out of 49 men diagnosed with idiopathic azoospermia from the Center for Fertility and Reproductive Endocrinology at Magee-Womens Hospital of UPMC,
and the Institute of Human Genetics of the Polish Academy of Sciences
in Poznan, Poland. Also, TEX11 gene errors were found in five out of 240
infertile men from the Center of Reproductive Medicine and Andrology in
Münster, Germany.
Dr. Yatsenko noted that it might be possible for an older father,
whose precursor sperm cells have a greater likelihood of acquiring a
mutation, to pass along the genetic error to his daughter, which could
make it impossible for her son to make viable sperm. Also, men without
seminal sperm who undergo a procedure to have a few rare, viable sperm
extracted from the testes to attempt conception with in vitro
fertilization could unknowingly pass a TEX11 gene mutation to a
daughter, making her a carrier.
“This research suggests screening for TEX11 gene mutations might be
useful in cases of otherwise unexplained azoospermia,” Dr. Yatsenko
said. “It might be possible to one day correct these problems with gene
therapy and other interventions. More work must be done to identify
other genetic causes of male infertility.”
The team included co-senior author Frank Tüttelmann, M.D., and
others from of the University of Münster, Germany; the University of
Pittsburgh; and the Polish Academy of Sciences.