Mating-Induced Increase in Germline Stem Cells via the Neuroendocrine System in Female Drosophila

Abstract

Mating and gametogenesis are two essential components of animal reproduction. Gametogenesis must be modulated by the need for gametes, yet little is known of how mating, a process that utilizes gametes, may modulate the process of gametogenesis. Here, we report that mating stimulates female germline stem cell (GSC) proliferation in Drosophila melanogaster. Mating-induced increase in GSC number is not simply owing to the indirect effect of emission of stored eggs, but rather is stimulated by a male-derived Sex Peptide (SP) and its receptor SPR, the components of a canonical neuronal pathway that induces a post-mating behavioral switch in females. We show that ecdysteroid, the major insect steroid hormone, regulates mating-induced GSC proliferation independently of insulin signaling. Ovarian ecdysteroid level increases after mating and transmits its signal directly through the ecdysone receptor expressed in the ovarian niche to increase the number of GSCs. Impairment of ovarian ecdysteroid biosynthesis disrupts mating-induced increase in GSCs as well as egg production. Importantly, feeding of ecdysteroid rescues the decrease in GSC number caused by impairment of neuronal SP signaling. Our study illustrates how female GSC activity is coordinately regulated by the neuroendocrine system to sustain reproductive success in response to mating.

Ovarian ecdysteroid biosynthesis and female germline stem cells

“…30 In addition, our data suggest that this activation, at least in part, results from transcriptional upregulation of ecdysteroidogenic enzyme-encoding genes. 30 On the other hand, several previous studies have reported that the ovarian ecdysteroid is detected in virgin females.…”

“…This is indeed the case, as our previous study has demonstrated that GSC number increases in response to mating. 30 Moreover, we also found that the mating-induced GSC increase is mediated by ovarian ecdysteroids. 30 In contrast, the underlying mechanisms that control ovarian ecdysteroid biosynthesis in virgin and mated females are still unknown.…”

“…Molecular genetics has revealed that ecdysteroid signaling is indeed active in adult insects, and is involved in controlling multiple steps during adult oogenesis, including egg chamber development and vitellogenesis, 27,28 follicle growth and survival, 9,29 and stem cell niche formation. 9 In addition, certain genes encoding the ecdysteroidogenic enzymes are required for egg development after stage 8, 19,26 egg production, 30 and border cell migration. 31 It is well-documented that, for the regulation of molting and metamorphosis, the biosynthesis and signaling of ecdysteroids are coordinately modulated in response to various environmental cues such as nutrition, photoperiod, and temperature.…”

Endocrine network essential for reproductive success in Drosophila melanogaster

“…Our experimental evidence suggests partner fecundity impairment could be because of a reduced rate of accessory gland protein synthesis in JH-deficient males. Accessory gland proteins have an indispensable role in stimulating female fecundity; sex peptide transfer can enhance reproductive output in females by stimulating JH synthesis, intestinal remodeling, and germ-line stem cell proliferation in females; and ovulin stimulates growth of octopaminergic neurons that regulate ovulation (34)(35)(36)(37)(38). By day 10, JH-deficient flies may have "caught up" to controls through accumulation of accessory gland proteins, providing sufficient protein ejaculate for normal egg production in the mated females.…”

Steroid signaling in mature follicles is important for Drosophila ovulation

“…Ecdysteroids have long been known to play essential roles in developmental transitions, such as larval molting and metamorphosis (27,28). In contrast, the roles of ecdysteroids in adult physiology have just started to emerge (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”