Developmental fluoxetine exposure facilitates sexual behavior in female offspring

Rayen, Ine; Steinbusch, Harry W.M.; Charlier, Thierry; Pawluski, Jodi L.

doi:10.1007/s00213-013-3215-5

Cited by 43 publications

(37 citation statements)

References 65 publications

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“…Exposure of adult male mice to BPA suppressed sexual motivation and performance [129]. Other environmental agents that perturb sexual behavior include fluoxetine [130], diesel exhaust [131], PBDE and PCB [132], and a long list of environmental toxicants/pollutants (reviewed by [104]). The modes of action appear to be wide ranging, including acting as anti-androgens/androgens, activation of steroid hormone receptors [133], and inhibition of activation enzymes such as aromatase [134].…”

Section: Developmental Origins Of Adult Reproductive Dysfunction Amentioning

confidence: 99%

Environmental factors, epigenetics, and developmental origin of reproductive disorders

Cheong

Adgent

et al. 2017

Reproductive Toxicology

185

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Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure to estrogenic and anti-androgenic endocrine disrupting chemicals (EDCs) is associated with reproductive dysfunction in adulthood. Human data in support of “Developmental Origins of Health and Disease” (DOHaD) comes from multigenerational studies on offspring of diethylstilbestrol-exposed mothers/grandmothers. Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by EDCs such as bisphenol A, genistein, diethylstilbestrol, p,p′-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons. Mechanisms underlying these EDC effects include direct mimicry of sex steroids or morphogens and interference with epigenomic sculpting during cell and tissue differentiation. Exposure to EDCs is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues. Here we review the literature exploring the connections between developmental exposure to EDCs and adult reproductive dysfunction, and the mechanisms underlying these effects.

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Section: Developmental Origins Of Adult Reproductive Dysfunction Amentioning

confidence: 99%

Environmental factors, epigenetics, and developmental origin of reproductive disorders

Cheong

Adgent

et al. 2017

Reproductive Toxicology

185

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“…Further relating to sex differences, FLX exposure may have effects on certain sexually dimorphic regions of the brain. This has not been well studied to date, but recently it has been reported that postnatal exposure to FLX in male (but not female) rats decreases the volume of the sexually dimorphic nucleus of the preoptic area in the hypothalamus, which is normally larger in males than in females, though it was not found to alter two other dimorphic regions of the brain, the posterior bed nucleus of the stria terminalis and the anteroventral periventricular nucleus [26,58]. Finally, serotonin may not be the only neurotransmitter system affected by developmental exposure to FLX.…”

Section: Neuroanatomical Outcomesmentioning

confidence: 99%

“…Other studies have found no effect on male sexual behaviour or motivation following prenatal or combined prenatal and postnatal exposure. Unlike in males, sexual behaviours in female rats are increased following postnatal exposure to FLX [58] (table 3). …”

Section: Long-term Behavioural Outcomesmentioning

confidence: 99%

Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

2013

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During and following pregnancy, women are at high risk of experiencing depression, for which fluoxetine (FLX; brand names Prozac, Sarafem, Rapiflux) is the most commonly prescribed treatment. An estimated 1.4-2.1% of pregnant women use this medication, which inhibits the reuptake of serotonin and thereby increases serotonergic activity at the synapse. Serotonin acts as a cue guiding numerous neurodevelopmental processes, and changes in the concentration of serotonin can disrupt normal in utero brain development and organization in humans and other animals, thus providing a mechanism by which maternal intake of FLX might alter neural development and ultimately behaviour. Despite this possibility, long-term alterations of behaviour and the brain have not been well studied in individuals exposed to FLX during pregnancy or soon after birth, perhaps because conducting such studies beyond infancy presents significant challenges. To remedy this problem, many researchers have turned to modelling the effects of developmental FLX exposure in non-human animals, primarily rodents. The body of literature on this topic has expanded considerably over the past several years, yet a comprehensive review is lacking. In order to fill this gap, we have summarized the findings of those studies describing the long-term behavioural and neurophysiological effects of FLX exposure in non-human animals in early development. We also discuss methodological considerations and common shortcomings of research in this area. The precise nature of the long-term effects of developmental FLX exposure remains difficult to specify, as these effects appear to be highly variable and dependent on numerous factors. Overall, however, it is clear that early FLX exposure in non-human animals can alter the development of the brain in ways that are relevant to behaviour in adulthood, decreasing exploration and social interaction, and in some cases altering anxiety- and depression-like behaviours.

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“…Previous studies of mice have demonstrated decreased sexual motivation following early exposure to Flx [25] and alterations in circadian behaviours [26]. Studies of rats have indicated changes in copulatory behaviours [27,28], decreased social exploration [18], increased vulnerability to the reinforcing effects of cocaine [29], and increased aggression [30]. Changes in depression-like behaviours were noted in both mice [20,21] and rats [22].…”

Section: Introductionmentioning

confidence: 99%

Increased Aggression, Improved Spatial Memory, and Reduced Anxiety-Like Behaviour in Adult Male Mice Exposed to Fluoxetine Early in Life

Kiryanova

Dyck

2014

Dev Neurosci

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Rationale: Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective serotonin reuptake inhibitor, is prescribed for the treatment of depression in pregnant women; however, this commonly prescribed medication could affect fetal brain development as Flx crosses the placenta. The available data concerning the anatomical and behavioural consequences of perinatal exposure to Flx during early development on adult behaviour are limited and often contradictory. Objectives: To further delineate the long-term behavioural effects of altering 5-HT during development, we examined the effects of perinatal Flx exposure on the behaviour of male mice as adults. Methods: Dams were treated with approximately 25 mg/kg/day of Flx from embryonic day 15 to postnatal day 12, and the behaviour of the adult offspring was assessed. Results: We found that perinatal Flx exposure leads to increased aggression, improved spatial memory, and reduced anxiety-like behaviour. This exposure did not cause memory deficits, changes in sensory processing, or changes in gross motor function. Conclusions: Our results suggest that while perinatal exposure to Flx may have long-term effects on adult behaviour, these effects appear limited and not necessarily detrimental.

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Developmental fluoxetine exposure facilitates sexual behavior in female offspring

Abstract: This research contributes in the understanding of the long-term impact developmental fluoxetine exposure on the hypothalamus-pituitary-gonadal (HPG) system in adult female offspring.

Cited by 43 publications

References 65 publications

Environmental factors, epigenetics, and developmental origin of reproductive disorders

Environmental factors, epigenetics, and developmental origin of reproductive disorders

Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

Increased Aggression, Improved Spatial Memory, and Reduced Anxiety-Like Behaviour in Adult Male Mice Exposed to Fluoxetine Early in Life

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