Tuesday, October 31, 2023
Why do some men not produce sperm? Scientists uncover one underlying reason for male infertility
Microscopy images showing normal seminiferous
tubules in control testes with mature sperm (black arrow: left) but smaller
empty seminiferous tubules in testes harboring a synaptonemal complex protein
point mutation (black asterisk: right). Credit: Stowers Institute for Medical
Research
Millions of
couples worldwide experience infertility with half of the cases originating in
men. For 10% of infertile males, little or no sperm are produced. Now, new
research from the Stowers Institute for Medical Research, in collaboration with
the Wellcome Center for Cell Biology at the University of Edinburgh, is
shedding light on what may be going wrong in the process of sperm formation,
leading to potential theories on possible treatments.
"A significant cause of infertility in males is
that they just cannot make sperm," said Stowers Investigator Scott Hawley,
Ph.D. "If you know exactly what is wrong, there are technologies emerging
right now that might give you a way to fix it."
The study published on October 20, 2023, in Science Advances from the Hawley Lab
and Wellcome Center Investigator Owen Davies, Ph.D., may help explain why some
men do not make enough sperm to fertilize an egg.
In most sexually-reproducing species, including humans, a critical protein structure resembling a lattice-like bridge needs to be built properly to produce sperm and egg cells. The team led by former Postdoctoral Research Associate Katherine Billmyre, Ph.D., discovered that in mice, changing a single and very specific point in this bridge caused it to collapse, leading to infertility and thus providing insight into human infertility in males due to similar problems with meiosis.
Stowers scientists collaborate to uncover one
underlying reason for male infertility. The study published on October 20,
2023, in Science Advances from the Hawley Lab and Wellcome
Centre Investigator Owen Davies, Ph.D., may help explain why some men do not
make enough sperm to fertilize an egg. Credit: Stowers Institute for Medical
Research
Meiosis, the cell division process giving rise to sperm and eggs, involves
several steps, one of which is the formation of a large protein structure
called the synaptonemal complex. Like a bridge, the complex holds chromosome
pairs in place enabling necessary genetic exchanges to occur that are essential
for the chromosomes to then correctly separate into sperm and eggs.
"A significant contributor to infertility is defects in meiosis,"
said Billmyre. "To understand how chromosomes separate into reproductive
cells correctly, we are really interested in what happens right before that
when the synaptonemal complex forms between them."
Previous studies have examined many proteins comprising the synaptonemal complex, how they interact with each other, and have identified various mutations linked to male infertility. The protein the researchers investigated in this study forms the lattices of the proverbial bridge, which has a section found in humans, mice, and most other vertebrates suggesting it is critical for assembly. Modeling different mutations in a potentially crucial region in the human protein enabled the team to predict which of these might disrupt protein function.
Model of the synaptonemal complex in control and
mutant mice. The protein the team investigated (SYCP1) forms normally, and all
additional necessary proteins are recruited. In the mutant, SYCP1 localizes to
the chromosome axes but does not successfully form the bridge-like structure
(head-to-head interactions), and the additional proteins that help keep the
bridge intact are either missing or not properly organized. Credit: Stowers
Institute for Medical Research
The authors
used a precise gene editing technique to make mutations in one key synaptonemal complex protein in mice, which allowed the researchers, for the first
time, to test the function of key regions of the protein in live animals. Just
a single mutation, predicted from the modeling experiments, was verified as the
culprit of infertility in mice.
"We're talking about pinpoint surgery here," said Hawley. "We focused on a tiny little region of one protein in this gigantic structure that we were pretty sure could be a significant cause of infertility."
Representative testes from nine-week-old control
mice (left) and mice with a point mutation in one synaptonemal complex protein
(right). Credit: Stowers Institute for Medical Research
Mice have long
been used as models for human diseases. From the modeling experiments using
human protein sequences, along with the high conservation of this protein
structure across species, the precise molecule that caused infertility in mice
likely functions the same way in humans.
"What is really exciting to me is that our
research can help us understand this really basic process that is necessary for
life," said Billmyre.
For Hawley, this research is a true representation of
the versatility of the Institute. Hawley's lab typically conducts research in fruit flies, yet the protein discovered in this study was not present in fruit
flies and demanded a different research organism to continue. Because of the
resources and Technology Centers at the Institute, it was possible to quickly
pivot and test the new infertility hypothesis in mice.
Additional authors include Emily A. Kesler, Dai Tsuchiya, Ph.D., Timothy J. Corbin, Kyle Weaver, Andrea Moran, Zulin Yu, Ph.D., Lane Adams, Kym Delventhal, Michael Durnin, Ph.D., and Owen Richard Davies, Ph.D.
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Monday, October 30, 2023
NASA’s Webb Makes First Detection of Heavy Element From Star Merger - UNIVERSE
Webb’s study of the second-brightest gamma-ray burst ever seen reveals tellurium.
A team of scientists has used
multiple space and ground-based telescopes, including NASA’s James Webb Space
Telescope, NASA’s Fermi Gamma-ray Space Telescope, and NASA’s Neil Gehrels
Swift Observatory, to observe an exceptionally bright gamma-ray burst, GRB
230307A, and identify the neutron star merger that generated an explosion that
created the burst. Webb also helped scientists detect the chemical element
tellurium in the explosion’s aftermath.
Image: Gamma-Ray Burst 230307A
This image from NASA’s James Webb Space Telescope NIRCam (Near-Infrared Camera) instrument highlights Gamma-Ray Burst (GRB) 230307A and its associated kilonova, as well as its former home galaxy, among their local environment of other galaxies and foreground stars. The GRB likely was powered by the merger of two neutron stars. The neutron stars were kicked out of their home galaxy and traveled the distance of about 120,000 light-years, approximately the diameter of the Milky Way galaxy, before finally merging several hundred million years later. Image: NASA, ESA, CSA, STScI, A. Levan (Radboud University and University of Warwick).
Other elements near tellurium on
the periodic table – like iodine, which is needed for much of life on Earth –
are also likely to be present among the kilonova’s ejected material. A kilonova
is an explosion produced by a neutron star merging with either a black hole or
with another neutron star.
“Just over 150 years since Dmitri
Mendeleev wrote down the periodic table of elements, we are now finally in the
position to start filling in those last blanks of understanding where
everything was made, thanks to Webb,” said Andrew Levan of Radboud University
in the Netherlands and the University of Warwick in the UK, lead author of the
study.
While neutron star mergers have
long been theorized as being the ideal “pressure cookers” to create some of the
rarer elements substantially heavier than iron, astronomers have previously
encountered a few obstacles in obtaining solid evidence.
Long Gamma-Ray Burst
Kilonovae are extremely rare,
making it difficult to observe these events. Short gamma-ray bursts (GRBs),
traditionally thought to be those that last less than two seconds, can be
byproducts of these infrequent merger episodes. (In contrast, long gamma-ray
bursts may last several minutes and are usually associated with the explosive
death of a massive star.)
The case of GRB 230307A is
particularly remarkable. First detected by Fermi in March, it is the second brightest GRB observed in over 50 years of
observations, about 1,000 times brighter than a typical gamma-ray burst that
Fermi observes. It also lasted for 200 seconds, placing it firmly in the
category of long duration gamma-ray bursts, despite its different origin.
“This burst is way into the long
category. It’s not near the border. But it seems to be coming from a merging
neutron star,” added Eric Burns, a co-author of the paper and member of the
Fermi team at Louisiana State University.
Opportunity: Telescope Collaboration
The collaboration of many
telescopes on the ground and in space allowed scientists to piece together a
wealth of information about this event as soon as the burst was first detected.
It is an example of how satellites and telescopes work together to witness
changes in the universe as they unfold.
After the first detection, an
intensive series of observations from the ground and from space, including
with Swift, swung into action to pinpoint the source on the sky and track how its
brightness changed. These observations in the gamma-ray, X-ray, optical,
infrared, and radio showed that the optical/infrared counterpart was faint,
evolved quickly, and became very red – the hallmarks of a kilonova.
“This type of explosion is very
rapid, with the material in the explosion also expanding swiftly,” said Om
Sharan Salafia, a co-author of the study at the INAF – Brera Astronomical
Observatory in Italy. “As the whole cloud expands, the material cools off
quickly and the peak of its light becomes visible in infrared, and becomes
redder on timescales of days to weeks.”
Image: Killanova – Webb vs Model
This graphic presentation compares the spectral data of GRB 230307A’s kilonova as observed by NASA’s James Webb Space Telescope and a kilonova model. Both show a distinct peak in the region of the spectrum associated with tellurium, with the area shaded in red. The detection of tellurium, which is rarer than platinum on Earth, marks Webb’s first direct look at an individual heavy element from a kilonova. Illustration: NASA, ESA, CSA, Joseph Olmsted (STScI).
At later times it would have been impossible to study this kilonova from
the ground, but these were the perfect conditions for Webb’s NIRCam
(Near-Infrared Camera) and NIRSpec (Near-Infrared Spectrograph) instruments to
observe this tumultuous environment. The spectrum has broad lines that show the material is ejected at high speeds, but one feature is
clear: light emitted by tellurium, an element rarer than platinum on Earth.
The highly sensitive infrared
capabilities of Webb helped scientists identify the home address of the two
neutron stars that created the kilonova: a spiral galaxy about 120,000
light-years away from the site of the merger.
Prior to their venture, they were
once two normal massive stars that formed a binary system in their home spiral galaxy. Since the duo was
gravitationally bound, both stars were launched together on two separate
occasions: when one among the pair exploded as a supernova and became a neutron star, and when the other star followed suit.
In this case, the neutron stars
remained as a binary system despite two explosive jolts and were kicked out of
their home galaxy. The pair traveled approximately the equivalent of the Milky
Way galaxy’s diameter before merging several hundred million years later.
Scientists expect to find even more
kilonovae in the future due to the increasing opportunities to have space and
ground-based telescopes work in complementary ways to study changes in the
universe. For example, while Webb can peer deeper into space than ever before,
the remarkable field of view of NASA’s upcoming Nancy
Grace Roman Space Telescope will enable astronomers to scout where and how frequently these
explosions occur.
“Webb provides a phenomenal boost
and may find even heavier elements,” said Ben Gompertz, a co-author of the
study at the University of Birmingham in the UK. “As we get more frequent
observations, the models will improve and the spectrum may evolve more in time.
Webb has certainly opened the door to do a lot more, and its abilities will be
completely transformative for our understanding of the universe.”
These findings
have been published in the journal Nature.
The James Webb Space Telescope is the world’s premier space science observatory. Webb is solving mysteries in our solar system, looking beyond to distant worlds around other stars, and probing the mysterious structures and origins of our universe and our place in it. Webb is an international program led by NASA with its partners, ESA (European Space Agency) and the Canadian Space Agency.
Source: NASA’s Webb Makes First Detection of Heavy Element From Star Merger - NASA
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