YSM Issue 97.1
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FOCUS<br />
Genetics<br />
SINK<br />
SWIM<br />
When sperm lose their ability to<br />
swim, the chances of conception<br />
take a dip as well. Around eighty<br />
percent of male patients with infertility have<br />
defects in their sperm motility, which refers<br />
to the sperm’s ability to move effectively<br />
and ultimately reach and fertilize an egg.<br />
Yet pinpointing the exact causes of these<br />
defects is surprisingly difficult.<br />
In a recent study, researchers from the<br />
Yale School of Medicine and Quaid-i-<br />
Azam University in Pakistan collaborated<br />
to tackle this problem. “The majority of<br />
the mutations of these kinds of fertility<br />
OR<br />
A New Explanation for Male Infertility<br />
BY ANYA RAZMI<br />
ART BY LUNA AGUILAR<br />
genes are really hard to identify because,<br />
by nature, infertility genes or mutations<br />
affecting fertility don’t pass on to the next<br />
generation,” said Jean-Ju Chung, a senior<br />
author on the study.<br />
Pakistani colleagues on Chung’s team<br />
collected blood and semen samples from the<br />
members of a family with hereditary male<br />
infertility caused by low sperm motility.<br />
Because the samples had similar genetics,<br />
it was easier to isolate which mutation<br />
was specifically tied to infertility. Using<br />
a type of DNA sequencing called whole<br />
exome sequencing, the scientists were able<br />
to identify a gene mutation that caused a<br />
defect in a protein component of sperm<br />
called leucine-rich repeat-containing 23<br />
(LRRC23). LRRC23 was truncated, meaning<br />
the protein was cut short.<br />
This left scientists with a question:<br />
how exactly might this defective protein<br />
cause infertility?<br />
Demystifying the Role of LRRC23<br />
Using CRISPR/Cas9, a gene-editing<br />
technology that allows researchers to<br />
target specific DNA sequences, the team<br />
was able to reproduce the human mutation<br />
in mice. Then, they studied sperm cells<br />
from the animals via a computer-assisted<br />
sperm analyzer to measure sperm motility.<br />
Live sperm cells were recorded using a<br />
video camera and their movement was<br />
tracked using special software which<br />
calculated the velocity and path of each<br />
cell. The data showed exactly what the<br />
scientists expected: the sperm could not<br />
swim properly, and the mice were infertile.<br />
“Biology is intricate and everything should<br />
be coordinated,” Chung said. Therefore,<br />
a structural defect in a single protein can<br />
affect the entire movement of the sperm.<br />
Sperm swim using flagella—small, hairlike<br />
structures that beat back and forth<br />
to generate cell movement. Flagella are<br />
composed of nine sets of microtubules:<br />
12 Yale Scientific Magazine March 2024 www.yalescientific.org