In utero and lactational exposure to fluoxetine delays puberty onset in female rats offspring

Santos, Alice Hartmann dos; Vieira, Milene Leivas; Camin, Nathália de Azevedo; Anselmo-Franci, Janete Aparecida; Ceravolo, Graziela Scalianti; Pelosi, Gislaine Garcia; Moreira, Estefânia Gastaldello; Kiss, Ana Carolina Inhasz; Mesquita, Suzana de Fátima Paccola; Gerardin, Daniela Cristina Ceccatto

doi:10.1016/j.reprotox.2016.04.006

Cited by 23 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the current state of research, the mechanism explaining early female vulnerability to maternal fluoxetine exposure is unclear. A lower dose of maternal postpartum FLX (5 mg/kg; s.c.) delays pubertal onset in female rats [55] and increases sexual behavior in adult female rats [57]. Thus, maternal postpartum FLX can impact development of female endocrine physiology which could alter hippocampal plasticity.…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

et al. 2017

View full text Add to dashboard Cite

BackgroundPostpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Postpartum depression can be treated with prescription antidepressants like fluoxetine (FLX). However, FLX can remain active in breast milk, raising concerns about the consequences of neonatal FLX exposure. The hippocampus is highly sensitive to developmental stress, and males and females respond differently to stress at many endpoints, including hippocampal plasticity. However, it is unclear how developmental exposure to FLX alters the trajectory of hippocampal development. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum depression) and concurrent FLX on hippocampal neurogenesis in male and female offspring.MethodsFemale Sprague-Dawley rat dams were treated daily with either CORT or oil and FLX or saline from postpartum days 2–23. Offspring were perfused on postnatal day 31 (pre-adolescent), postnatal day 42 (adolescent), and postnatal day 69 (adult). Tissue was processed for doublecortin (DCX), an endogenous marker of immature neurons, in the dorsal and ventral hippocampus.ResultsMaternal postpartum CORT reduced density of DCX-expressing cells in the dorsal hippocampus of pre-adolescent males and increased it in adolescent males, suggesting that postpartum CORT exposure disrupted the typical progression of the density of DCX-expressing cells. Further, among offspring of oil-treated dams, pre-adolescent males had greater density of DCX-expressing cells than pre-adolescent females, and maternal postpartum CORT prevented this sex difference. In pre-adolescent females, maternal postpartum FLX decreased the density of DCX-expressing cells in the dorsal hippocampus compared to saline. As expected, maternal CORT reduced the density of DCX-expressing cells in adult female, but not male, offspring. The combination of maternal postpartum CORT/FLX diminished density of DCX-expressing cells in dorsal hippocampus regardless of sex or age.ConclusionsThese findings reveal how modeling treatment of postpartum depression with FLX alters hippocampal neurogenesis in developing offspring differently depending on sex, predominantly in the dorsal dentate gyrus and earlier in life.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In one of these studies, prenatal fluoxetine treatment did not change puberty onset and pubertal weight (Moore et al, ). However, in another study, prenatal and lactational exposure to fluoxetine delayed puberty onset in female rats (dos Santos et al, ). The effect of serotonin on the reproductive system is thought to be via the hypothalamus and the studies indicate the presence of synapses between serotonergic neurons and GnRH neurons.…”

Section: Discussionmentioning

confidence: 93%

“…In relation to the effects of paroxetine treatment on the puberty onset, there has been only two prenatal SSRI treatment studies (dos Santos et al, ; Moore et al, ). In one of these studies, prenatal fluoxetine treatment did not change puberty onset and pubertal weight (Moore et al, ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of long‐term paroxetine or bupropion treatment on puberty onset, reproductive and feeding parameters in adolescent male rats

et al. 2019

View full text Add to dashboard Cite

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21–90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.

show abstract

“…Male rats show a peak of serotonin at PND3, while female rats have stable serotonin levels across development with a later peak in lifetime (Connell et al, 2004). Also, developmental exposure to Flx can deregulate the neuroendocrine hormonal control of female rats during prepubertal and pubertal periods (Dos Santos et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Postnatal exposure to fluoxetine led to cognitive‐emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats

Meurer

Linhares

Lima

et al. 2021

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

The exposure to selective serotonin reuptake inhibitors (SSRIs) during development results in behavioural impairment in adulthood in humans and animal models. Indeed, serotonergic overexpression in early life leads to structural and functional changes in brain circuits that control cognition and emotion. However, the effects of developmental exposure to these substances on the behaviour of adolescent rats are conflicting and remain poorly characterised. We performed a behavioural screening to investigate the effects of postnatal exposure to fluoxetine on memory and behaviours related to anxiety, anhedonia, and depression, as well we evaluate the parvalbumin expression in hippocampus of juvenile (~PND45) female and male rats. Fluoxetine (daily 20 mg/kg s.c. injections from PND7‐PND21)‐ or vehicle‐treated adolescent rats went through several behavioural tasks (from PND 38 to PND52) and were subject to transcardial perfusion and brain removal for immunohistochemical analysis (PND53). We found that postnatal exposure to fluoxetine increased anxiety‐ and depression‐like behaviours in the open field and sucrose preference and forced swimming tests, respectively. In addition, this treatment induced working memory and short‐term (but not long‐term) recognition memory impairments, and reduced parvalbumin‐positive interneurons in the hippocampus. In addition, the results revealed developmental sex‐dependent effects of fluoxetine postnatal treatment on adolescent rats' behaviour. These outcomes indicate that affective disorders and mnemonic alterations caused by SSRIs perinatal exposure can be present at adolescence.

show abstract

In utero and lactational exposure to fluoxetine delays puberty onset in female rats offspring

Cited by 23 publications

References 41 publications

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

Effects of long‐term paroxetine or bupropion treatment on puberty onset, reproductive and feeding parameters in adolescent male rats

Postnatal exposure to fluoxetine led to cognitive‐emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats

Contact Info

Product

Resources

About