DeLeon and her team made their discovery using the high-powered, three-dimensional super-resolution microscope that UD acquired in 2012.
The technology, whose inventors won the Nobel Prize in 2014, can
illuminate what’s happening in a cell, right down to a single molecule.
The oviductosomes from a female mouse were pre-labeled with a
fluorescent dye and incubated together with the sperm. Within an hour,
the oviductosomes were fused to the sperm’s surface. After two to three
hours, the oviductosomes continued to accumulate, primarily on the
sperm’s head and the midpiece of its tail.
Integrins, which are membrane receptors on both the sperm and the
oviductosomes, helped to facilitate their bonding, along with fusion
stalks on the sperm’s surface.
“Discovery of these oviductosomes provides us with a window into the
cargo being delivered by the female to the sperm,” DeLeon says. “The
implication is that we could improve IVF with this knowledge.”
IVF, or in vitro fertilization, currently has a 32 percent success
rate, and couples for whom the procedure fails face the puzzling,
disappointing reality that they can’t have a child of their own. Even
when the process works, a high sperm-to-egg ratio is required, the
opposite of what occurs in the body.
“We’ve shown that these oviductosomes are carrying critical molecules
that include not only proteins, but also nucleic acids such as RNA and
also lipids,” DeLeon says. “That gives us hope they can be used as
vehicles for improving fertility and the chances of producing healthy
embryos and offspring.”
Currently, DeLeon and her team are analyzing the protein-rich
contents of this cargo to find out exactly what gives the sperm what it
needs for its last push to penetrate the egg — always head first, tail
out — to fertilize it.
As for the calcium clearance pump, the sperm needs to use it to
reduce toxic calcium levels quickly. Otherwise, the sperm risks a
buildup of nitric oxide, which can cause DNA damage.
“Our work may lead to the discovery of genes and gene products that
cause infertility,” DeLeon says of the team’s continuing research. “We
may identify proteins required to improve the efficiency of IVF, and
improve the outcome and health of the offspring. It’s really another
step in the direction of personalized medicine, since individuals
carrying mutations of one of a variety of genes account for the largest
group of infertile couples.”
DeLeon has been making major contributions to reproductive science
since she published her first scientific article — “Cannabis and
Chromosomes,” examining the impact of marijuana on embryonic cells — in The Lancet in 1969, as a master’s student at the University of the West Indies in her native Jamaica.
The response to that paper was so dramatic, with requests for copies
from scientists around the world, that DeLeon set her sights on a career
in research and teaching and never looked back, continuing on for her
doctorate at the University of Western Ontario. She joined the UD
faculty in 1976.
DeLeon’s co-authors on the study include Amal A. Al-Dossary, who
graduated with her doctorate from UD last December and is now a
professor at the University of Dammam in Saudi Arabia; Pradeepthi
Bathala, who is pursuing her master’s degree at UD; and Jeffrey Caplan,
director of the BioImaging Center at the Delaware Biotechnology
Institute.
About the research sponsors:
Part of the National Institutes of Health (NIH), the National
Institute of Child Health and Human Development has primary
responsibility for conducting and supporting basic, translational, and
clinical research in the biomedical, behavioral, and social sciences
related to child and maternal health, in medical rehabilitation and in
the reproductive sciences.
The Delaware IDeA Network of Biomedical Research Excellence (INBRE)
is funded by a grant from the NIH-National Institute of General Medical
Sciences and by the state of Delaware to continue building a
self-sustaining basic and translational biomedical research capability
in Delaware.
