Ovulation in Drosophila is controlled by secretory cells of the female reproductive tract

Sun, Jianjun; Spradling, Allan C.

doi:10.7554/elife.00415

Cited by 86 publications

(111 citation statements)

References 56 publications

(90 reference statements)

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“…In doubly -mated Drosophila females, the timing of MP ejection influences paternity-the later that MP ejection occurs, the more progeny are sired by a second mating male (Lüpold et al 2013). Female molecular contributions to MP formation and/or ejection may be found among secreted components of the female reproductive tract (Allen and Spradling 2008;Prokupek et al 2009;Schnakenberg et al 2011;Wong et al 2012;Sun and Spradling 2013), neuromodulators (Avila et al 2012;Heifetz et al 2014), and/or innervation (Middleton et al 2006;Rubinstein and Wolfner 2013) required for fertility. In particular, a recent study showed that the activity of the neuropeptide diuretic hormone 44 in a subset of doublesex-expressing neurons is required for MP ejection (Lee et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme

et al. 2015

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Within the mated reproductive tracts of females of many taxa, seminal fluid proteins (SFPs) coagulate into a structure known as the mating plug (MP). MPs have diverse roles, including preventing female remating, altering female receptivity postmating, and being necessary for mated females to successfully store sperm. The Drosophila melanogaster MP, which is maintained in the mated female for several hours postmating, is comprised of a posterior MP (PMP) that forms quickly after mating begins and an anterior MP (AMP) that forms later. The PMP is composed of seminal proteins from the ejaculatory bulb (EB) of the male reproductive tract. To examine the role of the PMP protein PEBme in D. melanogaster reproduction, we identified an EB GAL4 driver and used it to target PEBme for RNA interference (RNAi) knockdown. PEBme knockdown in males compromised PMP coagulation in their mates and resulted in a significant reduction in female fertility, adversely affecting postmating uterine conformation, sperm storage, mating refractoriness, egg laying, and progeny generation. These defects resulted from the inability of females to retain the ejaculate in their reproductive tracts after mating. The uncoagulated MP impaired uncoupling by the knockdown male, and when he ultimately uncoupled, the ejaculate was often pulled out of the female. Thus, PEBme and MP coagulation are required for optimal fertility in D. melanogaster. Given the importance of the PMP for fertility, we identified additional MP proteins by mass spectrometry and found fertility functions for two of them. Our results highlight the importance of the MP and the proteins that comprise it in reproduction and suggest that in Drosophila the PMP is required to retain the ejaculate within the female reproductive tract, ensuring the storage of sperm by mated females.KEYWORDS mating plug; sperm storage; PEBme; Drosophila reproduction I N numerous species comprising diverse taxa, a solidified structure forms inside the female reproductive tract during (or shortly after) mating that is referred to as the mating plug (MP; also called the copulatory plug; we will refer to these structures collectively as MPs). MPs are largely a coagulation of male seminal fluid components. In species that produce a MP, its role in reproduction varies. In some species, MP formation is thought to guard against sperm competition. For example, in primates, MPs are seen most often in species whose females mate multiply (Dixson and Anderson 2002). Primate MPs have been suggested to prevent remating (Dorus et al. 2004), thus acting as a form of passive mate guarding (Dunham and Rudolf 2009). In the mouse, perturbing (Murer et al. 2001) or preventing (Dean 2013) MP formation reduces male fertility; in the absence of MP formation, sperm migration to the sites of fertilization is impaired (Dean 2013) receptivity in the short term (Polak et al. 1998;Bretman et al. 2010). In bumblebees, MPs physically switch off receptivity Sauter et al. 2001) and have functions related to sperm competition (Duvo...

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Section: Discussionmentioning

confidence: 99%

Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme

et al. 2015

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“…Both Nep1 and Nep2 are highly expressed in the CNS and the spermathecae, two tissues that are known to influence egg laying (Yang et al 2009;Schnakenberg et al 2011;Sun and Spradling 2013). Nep2 is also expressed in the border cells of the follicular epithelium, which are important for micropyle development and for anterior-posterior polarity in the egg (Furriols et al 2007).…”

Section: Characterization Of the Hatchability Defects In Nep2 Null Mumentioning

confidence: 99%

Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila

et al. 2014

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Members of the M13 class of metalloproteases have been implicated in diseases and in reproductive fitness. Nevertheless, their physiological role remains poorly understood. To obtain a tractable model with which to analyze this protein family's function, we characterized the gene family in Drosophila melanogaster and focused on reproductive phenotypes. The D. melanogaster genome contains 24 M13 class protease homologs, some of which are orthologs of human proteases, including neprilysin. Many are expressed in the reproductive tracts of either sex. Using RNAi we individually targeted the five Nep genes most closely related to vertebrate neprilysin, Nep1-5, to investigate their roles in reproduction. A reduction in Nep1, Nep2, or Nep4 expression in females reduced egg laying. Nep1 and Nep2 are required in the CNS and the spermathecae for wild-type fecundity. Females that are null for Nep2 also show defects as hosts of sperm competition as well as an increased rate of depletion for stored sperm. Furthermore, eggs laid by Nep2 mutant females are fertilized normally, but arrest early in embryonic development. In the male, only Nep1 was required to induce normal patterns of female egg laying. Reduction in the expression of Nep2-5 in the male did not cause any dramatic effects on reproductive fitness, which suggests that these genes are either nonessential for male fertility or perform redundant functions. Our results suggest that, consistent with the functions of neprilysins in mammals, these proteins are also required for reproduction in Drosophila, opening up this model system for further functional analysis of this protein class and their substrates. P ROTEASES play key roles in diverse physiological systems. One such family of metalloproteases, the M13 class of neutral endopeptidases, consists mainly of membranebound zinc proteases that are involved in the processing of neuropeptides and peptide hormones (reviewed in Turner et al. 2000;Turner et al. 2001;Bland et al. 2008). In mammals, seven members of this family have been identified, of which neprilysin (NEP) and endothelin converting enzyme (ECE) are the best studied. These proteins have been implicated in various diseases including cardiovascular disease (Segura and Ruilope 2011;Wick et al. 2011), Alzheimer's disease (Mulder et al. 2012;Klein et al. 2013), inflammation and inflammatory disorders (Wong et al. 2011), and cancer (Smollich et al. 2007;Maguer-Satta et al. 2011).In addition to their role in disease, NEPs are essential for development and reproduction in mammals. The mammalian Neprilysin-2, called NL1 in mice, is highly expressed in the testis. NL1-deficient males sire fewer pups, even though spermatogenesis appears to be unaffected (Carpentier et al. 2004). In females, NEP expression in the uterus is modulated by estrogen treatment in rats (Pinto et al. 1999) and during the estrogen/progesterone cycle in humans (Head et al. 1993). In female rats and mice, controlled degradation of tachykinins, particularly substance-P, by NEP in the uterus ...

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“…OA binds to its receptor Octopamine receptor in mushroom body (Oamb) in mature follicle cells to induce an intracellular calcium rise, Mmp2 activation, and follicle rupture (12). Drosophila ovulation is also regulated by multiple ovarian extrinsic factors, including secretions from the oviduct (13), female reproductive glands (14), and male accessory glands (15,16). However, a role for steroid signaling in Drosophila ovulation has never been established.…”

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confidence: 99%

Steroid signaling in mature follicles is important for Drosophila ovulation

Knapp

Sun

2017

Proc. Natl. Acad. Sci. U.S.A.

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Although ecdysteroid signaling regulates multiple steps in oogenesis, it is not known whether it regulates Drosophila ovulation, a process involving a matrix metalloproteinase-dependent follicle rupture. In this study, we demonstrated that ecdysteroid signaling is operating in mature follicle cells to control ovulation. Moreover, knocking down shade (shd), encoding the monooxygenase that converts ecdysone (E) to the more active 20-hydroxyecdysone (20E), specifically in mature follicle cells, blocked follicle rupture, which was rescued by ectopic expression of shd or exogenous 20E. In addition, disruption of the Ecdysone receptor (EcR) in mature follicle cells mimicked shd-knockdown defects, which were reversed by ectopic expression of EcR.B2 but not by EcR.A or EcR.B1 isoforms. Furthermore, we showed that ecdysteroid signaling is essential for the proper activation of matrix metalloproteinase 2 (Mmp2) for follicle rupture. Our data strongly suggest that 20E produced in follicle cells before ovulation activates EcR.B2 to prime mature follicles to be responsive to neuronal ovulatory stimuli, thus providing mechanistic insights into steroid signaling in Drosophila ovulation.steroid signaling | ecdysone | ovulation | Shade | EcR isoforms

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Ovulation in Drosophila is controlled by secretory cells of the female reproductive tract

Cited by 86 publications

References 56 publications

Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme

Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme

Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila

Steroid signaling in mature follicles is important for Drosophila ovulation

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