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Targeting sperm protection to combat malaria

Anopheles gambiae mosquito

Credit: CDC

New research has revealed a strategy for impairing fertility in malaria-carrying mosquitoes, potentially providing a tactic for combatting the disease.

Anopheles gambiae mosquitoes are the main transmitters of malaria, and the females mate only once during their lives.

They store the sperm from this single mating in an organ called the spermatheca, from which they repeatedly take sperm over the course of their lifetime to fertilize the eggs they lay.

The new research, published in PNAS, reveals that the sperm are partly protected by the actions of an enzyme called HPX15.

When researchers interfered with HPX15 in female A gambiae mosquitoes in the lab, the mosquitoes fertilized fewer eggs and, therefore, produced fewer offspring.

The team injected the female mosquitoes with an inhibitor to reduce the levels of HPX15. Normally, around 3% of the eggs a female lays do not develop into offspring. When the researchers reduced the levels of HPX15 in female mosquitoes, 20% of the mosquitoes’ eggs were infertile.

“[W]e reduced the number of offspring by a fifth, and that’s not a huge reduction,” said study author Flaminia Catteruccia, PhD, of the Harvard School of Public Health in Boston and the University of Perugia in Italy.

“But mosquitoes in the laboratory are subjected to much less stress than those in the wild, so we suspect that this kind of intervention would have a bigger impact on the fertility of wild mosquitoes. That’s something we would ultimately hope to investigate.”

The researchers also discovered how HPX15 is activated, suggesting another possible target for immobilizing the enzyme. The male mosquito transfers the hormone 20E to the female during mating, and it is this hormone that induces the expression of HPX15 in the female.

“The next step for this research is to think about how we could prevent activation of either the enzyme that protects the sperm, HPX15, or of the male trigger, 20E, that kicks that enzyme into action,” Dr Catteruccia said. “There may also be other pathways that we could target, and this is something that we’re keen to investigate.”

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Anopheles gambiae mosquito

Credit: CDC

New research has revealed a strategy for impairing fertility in malaria-carrying mosquitoes, potentially providing a tactic for combatting the disease.

Anopheles gambiae mosquitoes are the main transmitters of malaria, and the females mate only once during their lives.

They store the sperm from this single mating in an organ called the spermatheca, from which they repeatedly take sperm over the course of their lifetime to fertilize the eggs they lay.

The new research, published in PNAS, reveals that the sperm are partly protected by the actions of an enzyme called HPX15.

When researchers interfered with HPX15 in female A gambiae mosquitoes in the lab, the mosquitoes fertilized fewer eggs and, therefore, produced fewer offspring.

The team injected the female mosquitoes with an inhibitor to reduce the levels of HPX15. Normally, around 3% of the eggs a female lays do not develop into offspring. When the researchers reduced the levels of HPX15 in female mosquitoes, 20% of the mosquitoes’ eggs were infertile.

“[W]e reduced the number of offspring by a fifth, and that’s not a huge reduction,” said study author Flaminia Catteruccia, PhD, of the Harvard School of Public Health in Boston and the University of Perugia in Italy.

“But mosquitoes in the laboratory are subjected to much less stress than those in the wild, so we suspect that this kind of intervention would have a bigger impact on the fertility of wild mosquitoes. That’s something we would ultimately hope to investigate.”

The researchers also discovered how HPX15 is activated, suggesting another possible target for immobilizing the enzyme. The male mosquito transfers the hormone 20E to the female during mating, and it is this hormone that induces the expression of HPX15 in the female.

“The next step for this research is to think about how we could prevent activation of either the enzyme that protects the sperm, HPX15, or of the male trigger, 20E, that kicks that enzyme into action,” Dr Catteruccia said. “There may also be other pathways that we could target, and this is something that we’re keen to investigate.”

Anopheles gambiae mosquito

Credit: CDC

New research has revealed a strategy for impairing fertility in malaria-carrying mosquitoes, potentially providing a tactic for combatting the disease.

Anopheles gambiae mosquitoes are the main transmitters of malaria, and the females mate only once during their lives.

They store the sperm from this single mating in an organ called the spermatheca, from which they repeatedly take sperm over the course of their lifetime to fertilize the eggs they lay.

The new research, published in PNAS, reveals that the sperm are partly protected by the actions of an enzyme called HPX15.

When researchers interfered with HPX15 in female A gambiae mosquitoes in the lab, the mosquitoes fertilized fewer eggs and, therefore, produced fewer offspring.

The team injected the female mosquitoes with an inhibitor to reduce the levels of HPX15. Normally, around 3% of the eggs a female lays do not develop into offspring. When the researchers reduced the levels of HPX15 in female mosquitoes, 20% of the mosquitoes’ eggs were infertile.

“[W]e reduced the number of offspring by a fifth, and that’s not a huge reduction,” said study author Flaminia Catteruccia, PhD, of the Harvard School of Public Health in Boston and the University of Perugia in Italy.

“But mosquitoes in the laboratory are subjected to much less stress than those in the wild, so we suspect that this kind of intervention would have a bigger impact on the fertility of wild mosquitoes. That’s something we would ultimately hope to investigate.”

The researchers also discovered how HPX15 is activated, suggesting another possible target for immobilizing the enzyme. The male mosquito transfers the hormone 20E to the female during mating, and it is this hormone that induces the expression of HPX15 in the female.

“The next step for this research is to think about how we could prevent activation of either the enzyme that protects the sperm, HPX15, or of the male trigger, 20E, that kicks that enzyme into action,” Dr Catteruccia said. “There may also be other pathways that we could target, and this is something that we’re keen to investigate.”

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