The Interaction between a Sexually Transferred Steroid Hormone and a Female Protein Regulates Oogenesis in the Malaria Mosquito Anopheles gambiae

Abstract

Steroid hormones transferred by the male during sex trigger a molecular cascade of events that increases the reproductive success of females in Anopheles gambiae mosquitoes.

Abstract

Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis ( MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria.

Author Summary

Anopheles gambiae mosquitoes are the most deadly vectors of human malaria. The reproductive ability of these mosquitoes contributes to their role as disease vectors as it ensures high population densities for malaria transmission. The number of eggs developed by females after blood feeding depends on whether they have previously mated. Indeed in natural mosquito populations, virgin females rarely develop eggs when blood fed. Here we report on the identification of a molecular interaction between 20-hydroxy-ecdysone (20E), a steroid hormone transferred by the male during sex, and the Mating-Induced Stimulator of Oogenesis (MISO), a female reproductive protein, expression of which is triggered by mating and leads to increased egg production. We show that the expression of MISO after mating is regulated by 20E via the Ecdysone receptor (EcR). Experimental silencing of MISO reduces the ability of mated females to develop eggs after blood feeding, by reducing expression of a vitellogenic lipid transporter. By showing how male mosquitoes contribute to oogenesis in females, we identify a molecular pathway that can be targeted to reduce the reproductive success of natural mosquito populations to aid malaria control.