Fertility:Key protein helps sperm do their job in timely fashion

Date:
August 20, 2021
Source:
University of California - San Diego
Summary:
Researchers detail how a ubiquitous signaling molecule plays a
critical role in male fertility, orchestrating key steps that
promote sperm motility, survival and fertilization success.



FULL STORY ========================================================================== Mammalian sperm cannot fertilize an egg from the get-go. It's an
ability acquired only after insemination, during passage through the
female reproductive tract, and requires two consecutive, time-sensitive processes to provide sperm with the physical and biochemical traits
necessary to complete their fundamental job.


==========================================================================
The first process is called capacitation, which alters the physiology of
each spermatozoa, changing the membrane of the head to help it penetrate
the hard, outer layer of an egg -- the zona pellucida -- and chemistry
in the tail to generate greater motility, the ability to move and swim.

The second process is acrosome reaction (AR), a chemical action that
involves releasing enzymes in the spermatozoa's head that further boost penetration of the zona pellucida.

Both processes are essential to successful fertilization of an egg, and AR
is time-dependent: It cannot take place too early or too late. Indeed, premature AR has been associated with idiopathic (spontaneous) male infertility.

Neither process, however, is well understood in terms of the underlying molecular mechanisms involved. In a new paper, publishing August
19, 2021 in the journal eLife, a team of researchers at University
of California San Diego School of Medicine detail how GIV/Girdin, a
ubiquitous signaling molecule plays a critical role in male fertility, orchestrating capacitation and AR to promote sperm motility, survival
and fertilization success.

Specifically, the research team, led by senior author Pradipta Ghosh,
MD, professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, found that GIV -- a member
of the G protein family that serve as molecular switches inside cells, transmitting and fine- tuning signals -- regulates the activity of
enzymes that turn on and turn off the processes of capacitation and AR.

"The findings demonstrate how GIV orchestrates distinct signaling
programs in sperm that separated by space and time, effectively supporting capacitation while inhibiting premature AR," said Ghosh. "As a result,
GIV plays an essential role in male fertility." Infertility affects
an estimated 8 to 12 percent of couples globally, with males being a
primary or contributing factor in roughly half of all cases, according to published studies. Causes of male infertility are multiple, but roughly
25 percent involve either sperm transport disorders or idiopathic factors
in sperm with no apparent dysfunction.

"GIV is required for male fertility, and low levels of GIV transcripts in
men is invariably associated with infertility," said Ghosh. "We've found evidence that GIV may perform different roles in the capacitation of
sperm, findings that shed new light on both how defective GIV-signaling
might be used as a potential marker for male infertility and how
inhibitors of GIV-dependent signaling inhibit fertility by reducing
sperm motility and viability and by promoting premature acrosome reaction.

"The latter, ironically enough, may be a promising strategy for
development of a male contraceptive pill specifically targeting sperm." Co-authors include: Sequoyah Reynoso, Vanessa Castillo, Gajanan D. Katkar, Inmaculada Lopez-Sanchez, Sahar Taheri, Celia R. Espinoza, Christina
Rohena, Debashis Sahoo and Pascal Gagneux, all at UC San Diego.

========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Scott La
Fee. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sequoyah Reynoso, Vanessa Castillo, Gajanan Dattatray Katkar,
Inmaculada
Lopez-Sanchez, Sahar Taheri, Celia Espinoza, Cristina Rohena,
Debashis Sahoo, Pascal Gagneux, Pradipta Ghosh. GIV/Girdin,
a non-receptor modulator for Gai/s, regulates spatiotemporal
signaling during sperm capacitation and is required for male
fertility. eLife, 2021; 10 DOI: 10.7554/eLife.69160 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210820111117.htm

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