Skip to main content

Table 1 Phenotypes associated with manipulating 20-hydroxyecdysone titers, activity or signaling in mosquitoes

From: 20-Hydroxyecdysone (20E) signaling as a promising target for the chemical control of malaria vectors

Method

Species

Phenotype

References

20E signaling regulates egg production and egg hatching

20E injection (engorged females)

An. freeborni

Longer retention of blood meal

[171]

20E injection (virgin females)

An. arabiensis, An. gambiae

Increased oviposition and refractoriness to further mating

[122]

EcR silencing (adult females)

Ae. aegypti

Reduced egg production

Inhibition genes involved in autophagy

Decreased size of ovarian follicles

Egg developmental defects (failure of eggs to develop after first oviposition)

[172]

EcR silencing (adult females)

An. gambiae

~ 74.4% decreased expression of MISO (gene regulating oogenesis and oviposition)

~ 54% decreased expression of Vg (gene regulating vitellogenesis)

[123]

EcR silencing (adult females)

An. gambiae

Reduced egg clutch size

[105]

USP silencing (adult females)

An. gambiae

Reduced correlation between egg production and pathogen development

[105]

20E agonist methoxyfenozide (eggs)

Cx. pipiens

46.99% inhibitory effect on egg hatchability

Slowed development

Atypical hatching observed

[131]

20E agonist halofenozide (4th instar larvae)

Cx. pipiens

Developmental abnormalities in newly eclose adults

23% reduction of hatch rate and 14% reduction of fecundity

[173]

20E agonist methoxyfenozide (adult females)

An. gambiae

95% reduction in egg batch size

98.7% of treated females lacked mature ovarian follicles

[23]

Reducing 20E titers and activity (adult males)

An. gambiae

Females mating with those 20E-impaired males fail to oviposit after blood feeding

[25]

Reducing 20E activity (adult females)

An. gambiae

Reduced egg clutch size

[105]

20E signaling regulates larval/pupal development

20E agonist halofenozide (4th instar larvae)

Cx. pipiens

Developmental abnormalities observed in larvae and pupae

Decreased body weight of fourth instar larvae due to decreased nutrient uptake

[173]

20E agonists RH-5849, RH-5992 & RH-2485 (larvae)

Ae. aegypti, Cx. quinquefasciatus, An. gambiae

Concentrations above 100 μg/100 ml resulted in 100% larval mortality in An. gambiae

Concentrations above 200 μg/100 ml resulted in 100% larval mortality in Ae. aegypti, Cx. quinquefasciatus

[26]

20E agonist methoxyfenozide (larvae)

C. morsitans

Premature moulting

High larval mortality

Incomplete pupation

Adult females that survived had reduced fecundity/fertility

[104]

20E agonist halofenozide (larvae)

Cx. pipiens

Reduced number of cuticular hydrocarbons in larvae

[174]

20E agonist halofenozide (larvae)

Cx. pipiens

Failure to ecdyse

Increased cuticular thickness

[175]

20E agonists

Tebufenozide, methoxyfenozide, halofenozide & KU-106 (larvae)

An. gambiae

Larval mortality

[27]

Feeding larvae with transgenic algae expressing dsRNA against HR3a

Ae. aegypti

Larvae died prematurely

Shorter larvae (body length)

Abnormal midgut morphology

Delay in life-cycle

[176]

20E signaling regulates mating, fecundity and longevity

20E injection (virgin females)

An. gambiae

Lifetime refractoriness to mating in females

Eggs laid were sterile

[25]

20E agonist methoxyfenozide (adult females)

An. gambiae

Reduction in mated females by 65%

Reduced longevity

[23]

20E signaling regulates mosquitoes’ ecdysteroid levels

Reducing 20E titer by silencing spook (adult females)

An. gambiae

Decreased ecdysteroid production in ovaries

[44]

Reducing 20E activity by injecting E220b

An. gambiae

Fourfold decreased ecdysteroid production 26 h after blood meal

[105]

20E signaling regulates Plasmodium and bacterial infection

20E agonist methoxyfenozide (adult females)

An. gambiae

Infection by Plasmodium falciparum reduced by 87%

[23]

20E agonist halofenozide (adult females)

An. gambiae

P. berghei infection prevalence reduced by ~ 40%

Reduction in oocyst intensity

[24]

20E agonist halofenozide (USP-silenced adult females)

An. gambiae

No effect on P. berghei infection prevalence

[24]

EcR silencing (adult females)

An. gambiae

Reduced P. falciparum oocyst prevalence by 11–24%

Reduced P. falciparum extrinsic incubation period, as indicated by earlier invasion of salivary glands with sporozoites

Higher infectious sporozoite prevalence and intensity in EcR-silenced females at 10 dpi and 12 dpi, respectively

[105]

Reducing 20E activity by injecting E220a (adult females)

An. gambiae

Reduced oocyst intensity

Reduced P. falciparum EIP, as indicated by earlier invasion of salivary glands with sporozoites

[105]

20E injection 24 h before infection (adult females)

An. gambiae

Reduced P. berghei oocyst prevalence and intensity

Reduced E. coli infection

[106]

20E injection 2 h after infection (adult females)

An. gambiae

No effect on P. berghei oocyst prevalence and intensity

[164]

20E injection (adult females)

An. coluzzii

P. falciparum oocyst prevalence increased by ~ 93%

P. falciparum oocyst intensity increased by > 100%

[125]

20E signaling regulates pyrethroid resistance

Reducing 20E titer by silencing spookiestc (adult females)

Cx. pipiens pallens

The resistant strain became increasingly susceptible to deltamethrin

[107]

Reducing 20E titer by silencing shadec (adult females)

Cx. pipiens pallens

The resistant strain became increasingly susceptible to deltamethrin

[108]

  1. Ae., Aedes; An., Anopheles; Cx., Culex; dpi, days post-inoculation; EcR, ecdysone receptor; 20E, 20-hydroxyecdysone; USP, ultraspiracle protein
  2. aHR3 is one of the “early genes” in the 20E signaling cascade; see Fig. 1b
  3. bE220, or ecdysone 22-oxidase, reduces 20E activity by converting the C22 hydroxyl group into a carbonyl group [177]
  4. cSpookiest and shade code for cytochrome P450 enzymes involved in 20E biosynthesis; see Fig. 1a