A male steroid controls female sexual behaviour in the malaria mosquito

• Published in: Nature (London) 2022-08, Vol.608 (7921), p.93-97
• Main Authors: Peng, Duo, Kakani, Evdoxia G., Mameli, Enzo, Vidoudez, Charles, Mitchell, Sara N., Merrihew, Gennifer E., MacCoss, Michael J., Adams, Kelsey, Rinvee, Tasneem A., Shaw, W. Robert, Catteruccia, Flaminia
• Format: Article
• Language: English
• Subjects: 13/1; 13/89; 38; 38/22; 38/23; 38/39; 38/77; 42/44; 631/443/494; 631/45/776/1176; 631/601/1466; 82/16; 82/58; 82/80; 82/83; Animal reproduction; Aquatic insects; Breeding success; Control programs; Dephosphorylation; Eggs; Enzymes; Females; Fertility; Gene expression; Genes; Hormones; Humanities and Social Sciences; Insects; Kinases; Malaria; Males; Mating; Mosquitoes; multidisciplinary; Oviposition; Parasites; Paternity; Phosphatase; Physiology; Plasmodium; Reproduction; Reproductive fitness; Science; Science (multidisciplinary); Sex; Sexual behavior; Sexual receptivity; Steroid hormones; Steroids; Thermal resistance; Vector-borne diseases; Vertebrates
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-022-04908-6

Insects, unlike vertebrates, are widely believed to lack male-biased sex steroid hormones 1 . In the malaria mosquito Anopheles gambiae , the ecdysteroid 20-hydroxyecdysone (20E) appears to have evolved to both control egg development when synthesized by females 2 and to induce mating refractoriness when sexually transferred by males 3 . Because egg development and mating are essential reproductive traits, understanding how Anopheles females integrate these hormonal signals can spur the design of new malaria control programs. Here we reveal that these reproductive functions are regulated by distinct sex steroids through a sophisticated network of ecdysteroid-activating/inactivating enzymes. We identify a male-specific oxidized ecdysteroid, 3-dehydro-20E (3D20E), which safeguards paternity by turning off female sexual receptivity following its sexual transfer and activation by dephosphorylation. Notably, 3D20E transfer also induces expression of a reproductive gene that preserves egg development during Plasmodium infection, ensuring fitness of infected females. Female-derived 20E does not trigger sexual refractoriness but instead licenses oviposition in mated individuals once a 20E-inhibiting kinase is repressed. Identifying this male-specific insect steroid hormone and its roles in regulating female sexual receptivity, fertility and interactions with Plasmodium parasites suggests the possibility for reducing the reproductive success of malaria-transmitting mosquitoes. The discovery of a male-specific sex hormone in the mosquito Anopheles gambiae may allow new strategies for the control of this notorious disease vector.