Delivering proteins to testes could someday treat male infertility


Date:
October 21, 2020
Source:
American Chemical Society
Summary:
According to the Mayo Clinic, about 15% of couples are infertile,
and male infertility plays a role in over one-third of these
cases. Often, problems with sperm development are to blame. Now,
researchers have found a way to deliver a protein important for
sperm cell production directly to mouse testicles, where it restored
normal sperm development and allowed previously infertile mice to
father pups.



FULL STORY ========================================================================== According to the Mayo Clinic, about 15% of couples are infertile, and
male infertility plays a role in over one-third of these cases. Often,
problems with sperm development are to blame. Now, researchers reporting
in ACS Nano have found a way to deliver a protein important for sperm
cell production directly to mouse testicles, where it restored normal
sperm development and allowed previously infertile mice to father pups.


==========================================================================
Male infertility often happens because of a lack of sperm in the semen,
which can result from damage to the blood-testis barrier (BTB). This
barrier protects reproductive cells from harmful toxicants and drugs,
and a protein called PIN1 is important for its function. Mice genetically engineered to lack PIN1 are infertile, with small testes, depleted sperm
stem cells and a low sperm count.

Although scientists have considered gene therapies to treat male
infertility, these procedures are risky because they could cause
unwanted genetic changes in reproductive cells that might be passed
onto offspring. Hyun-Mo Ryoo and colleagues wanted to develop a system
to deliver proteins (such as PIN1) instead of genes to the testes, but
first they had to find a way to get proteins through the complex tubes
of the testicles and into cells.

The researchers developed a delivery system called Fibroplex, which
consisted of spherical nanoparticles made of silk fibroin and a coating
of lipids. They loaded PIN1 into Fibroplex, and showed that the particles appeared safe and didn't show signs of toxicity or testicular damage in
mice. When the team injected the PIN1-loaded Fibroplex into the testes
of young mice with PIN1 deletions, the treatment restored nearly normal
PIN1 levels and sperm stem cell numbers and repaired the BTB. Treated mice
had normal testicular weight and size and about 50% of the sperm count of wild-type mice. Until about 5 months after treatment, when the protein degraded, the PIN1-Fibroplex-treated mice fathered a similar number
of pups as wild-type mice, whereas untreated mice with PIN1 deletions
remained infertile. This is the first demonstration of direct delivery of proteins into the testis to treat male infertility, the researchers say.


========================================================================== Story Source: Materials provided by American_Chemical_Society. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Woo Jin Kim, Bong Soo Kim, Hyun Jung Kim, Young Dan Cho, Hye
Lim Shin,
Hee In Yoon, Yun Sil Lee, Jeong-Hwa Baek, Kyung Mi Woo, Hyun-Mo
Ryoo.

Intratesticular Peptidyl Prolyl Isomerase 1 Protein Delivery Using
Cationic Lipid-Coated Fibroin Nanoparticle Complexes Rescues Male
Infertility in Mice. ACS Nano, 2020; DOI: 10.1021/acsnano.0c04936 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201021130145.htm

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