Dataset Information

Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay.

ABSTRACT: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is currently available on the market and is suspected of causing congenital malformations in babies born to mothers who take the drug during the first trimester of pregnancy. We utilized organismal performance assays (OPAs), a novel toxicity assessment method, to assess the safety of paroxetine during pregnancy in a rodent model. OPAs utilize genetically diverse wild mice (Mus musculus) to evaluate competitive performance between experimental and control animals as they compete among each other for limited resources in semi-natural enclosures. Performance measures included reproductive success, male competitive ability and survivorship. Paroxetine-exposed males weighed 13% less, had 44% fewer offspring, dominated 53% fewer territories and experienced a 2.5-fold increased trend in mortality, when compared with controls. Paroxetine-exposed females had 65% fewer offspring early in the study, but rebounded at later time points, presumably, because they were no longer exposed to paroxetine. In cages, paroxetine-exposed breeders took 2.3 times longer to produce their first litter and pups of both sexes experienced reduced weight when compared with controls. Low-dose paroxetine-induced health declines detected in this study that were undetected in preclinical trials with doses 2.5-8 times higher than human therapeutic doses. These data indicate that OPAs detect phenotypic adversity and provide unique information that could be useful towards safety testing during pharmaceutical development.

SUBMITTER: Gaukler SM

PROVIDER: S-EPMC4416947 | biostudies-literature | 2015 Jan-Feb

REPOSITORIES: biostudies-literature

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Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay.

Gaukler Shannon M SM Ruff James S JS Galland Tessa T Kandaris Kirstie A KA Underwood Tristan K TK Liu Nicole M NM Young Elizabeth L EL Morrison Linda C LC Yost Garold S GS Potts Wayne K WK

Neurotoxicology and teratology 20141112

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is currently available on the market and is suspected of causing congenital malformations in babies born to mothers who take the drug during the first trimester of pregnancy. We utilized organismal performance assays (OPAs), a novel toxicity assessment method, to assess the safety of paroxetine during pregnancy in a rodent model. OPAs utilize genetically diverse wild mice (Mus musculus) to evaluate competitive performance between ...[more]

PMID: 25446017

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Project description:One measure of habitat quality is a species' demographic performance in a habitat and the gold standard metric of performance is reproduction. Such a measure, however, may be misleading if individual quality is a fitness determinant. We report on factors affecting lifetime reproduction (LR), the total number of lifetime fledglings produced by an individual, and long-term territory-specific reproduction in a multi-generational study of northern goshawks (Accipiter gentilis). LR increased with longer lifespans and more breeding attempts and was strongly correlated with the number of recruits in two filial generations indicating that LR was a good fitness predictor. Extensive differences in LR attested to heterogeneity in individual quality, a requisite for the ideal pre-emptive distribution model (IPD) of habitat settling wherein high quality individuals get the best habitats forcing lower quality individuals into poorer habitats with lower reproduction. In response to 7‒9-year prey abundance cycles, annual frequency of territory occupancy by breeders was highly variable and low overall with monotonic increases in vacancies through low prey years. Occupancy of territories by breeders differed from random; some appeared preferred while others were avoided, producing a right-skewed distribution of total territory-specific fledgling production. However, mean fledglings per nest attempt was only slightly lower in less versus more productive territories, and, contrary to IPD predictions of increases in annual territory-specific coefficients of variation (CV) in reproduction as breeder densities increase, the CV of production decreased as density increased. Rather than habitat quality per se, conspecific attraction elicited territory selection by prospecting goshawks as 70% of settlers comprised turnovers on territories, resulting in occupancy continuity and increased territory-specific reproduction. Top-producing territories had as few as 2 long-lived (high LR) and up to 6 short-lived (low LR) sequential breeders. While individual quality appeared to effect territory-specific heterogeneity in reproductive performance, our data suggests that differences in individual quality may be washed-out by a random settling of prospectors in response to conspecific attraction.

Project description:BackgroundFighting disease while fighting rivals exposes males to constraints and trade-offs during male-male competition. We here tested how both the stage and intensity of infection with the fungal pathogen Metarhizium robertsii interfere with fighting success in Cardiocondyla obscurior ant males. Males of this species have evolved long lifespans during which they can gain many matings with the young queens of the colony, if successful in male-male competition. Since male fights occur inside the colony, the outcome of male-male competition can further be biased by interference of the colony's worker force.ResultsWe found that severe, but not yet mild, infection strongly impaired male fighting success. In late-stage infection, this could be attributed to worker aggression directed towards the infected rather than the healthy male and an already very high male morbidity even in the absence of fighting. Shortly after pathogen exposure, however, male mortality was particularly increased during combat. Since these males mounted a strong immune response, their reduced fighting success suggests a trade-off between immune investment and competitive ability already early in the infection. Even if the males themselves showed no difference in the number of attacks they raised against their healthy rivals across infection stages and levels, severely infected males were thus losing in male-male competition from an early stage of infection on.ConclusionsMales of the ant C. obscurior have a well-developed immune system that raises a strong immune response very fast after fungal exposure. This allows them to cope with mild pathogen exposures without compromising their success in male-male competition, and hence to gain multiple mating opportunities with the emerging virgin queens of the colony. Under severe infection, however, they are weak fighters and rarely survive a combat already at early infection when raising an immune response, as well as at progressed infection, when they are morbid and preferentially targeted by worker aggression. Workers thereby remove males that pose a future disease threat by biasing male-male competition. Our study thus reveals a novel social immunity mechanism how social insect workers protect the colony against disease risk.

Dataset Information

Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay.

Publications

Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay.

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