Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila

• Published in: Nature (London) 2020-08, Vol.584 (7821), p.415-419
• Main Authors: Ahmed, Sara Mahmoud H., Maldera, Julieta A., Krunic, Damir, Paiva-Silva, Gabriela O., Pénalva, Clothilde, Teleman, Aurelio A., Edgar, Bruce A.
• Format: Article
• Language: English
• Subjects: 13; 13/100; 13/21; 13/89; 631/136/2091; 631/443; 631/80/86/2363; 64; 64/24; 96; Age; Aging; Analysis; Animal reproduction; Animals; Carcinogenesis; Cell Proliferation; Copulation - physiology; Cytokines; Digestive system; Divisions; DNA-Binding Proteins - metabolism; Drosophila; Drosophila melanogaster - anatomy & histology; Drosophila melanogaster - cytology; Drosophila melanogaster - metabolism; Drosophila melanogaster - physiology; Drosophila Proteins - metabolism; Dysplasia; Ecdysone; Ecdysone - metabolism; Enzymes; Fecundity; Female; Females; Fertility - physiology; Fitness; Gastrointestinal tract; Genetic aspects; Growth; Hormones; Humanities and Social Sciences; Infections; Influence; Insects; Intestinal Mucosa - anatomy & histology; Intestinal Mucosa - cytology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Intestines - anatomy & histology; Intestines - cytology; Intestines - growth & development; Intestines - pathology; Life span; Longevity - physiology; Male; Males; multidisciplinary; Organ Size - physiology; Organs; Ovaries; Ovary - metabolism; Physiological aspects; Physiology; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Steroid - metabolism; Reproductive fitness; Reproductive organs; Risk factors; Science; Science (multidisciplinary); Sex; Sex hormones; Sexual dimorphism; Signaling; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Steroid hormone receptors; Steroids; Steroids - metabolism; Tradeoffs; Transcription Factors - metabolism; Tumorigenesis
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2462-y

Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences 1 – 3 . How sex hormones affect non-reproductive organs is poorly understood, yet highly relevant to health given the sex-biased incidence of many diseases 4 . Here we report that steroid signalling in Drosophila from the ovaries to the gut promotes growth of the intestine specifically in mated females, and enhances their reproductive output. The active ovaries of the fly produce the steroid hormone ecdysone, which stimulates the division and expansion of intestinal stem cells in two distinct proliferative phases via the steroid receptors EcR and Usp and their downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent growth of the female gut augments fecundity, the more active and more numerous intestinal stem cells also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, thus potentially reducing lifespan. This work highlights the trade-offs in fitness traits that occur when inter-organ signalling alters stem-cell behaviour to optimize organ size. High levels of the sexually dimorphic hormone ecdysone, produced by active ovaries in Drosophila , promote the proliferation of stem cells in the female gut and maximize reproductive fitness, but also increase female susceptibility to age-dependent dysplasia and tumorigenesis.