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Ancestral Fluoxetine Exposure Sensitizes Zebrafish to Venlafaxine-Induced Reductions in Cortisol and Spawning.

Abstract：

:Owing to the prevalence of depression during childbearing, mothers can be prescribed multiple antidepressants; however, little is known about the risk and consequences to the offspring or subsequent generations. Fluoxetine (FLX) is usually the first-line of pharmacological treatment for affective disorders in pregnant women, with venlafaxine (VEN) used as secondary treatment. Given that FLX and VEN readily cross the placenta, a fetus from a treated pregnant woman is potentially at risk of the endocrine disruptive effects of these chemicals. Pharmaceutical agents, including FLX and VEN, reach aquatic ecosystems through sewage release; thus, fish could also be inadvertently affected. We report the results from a 6-day FLX exposure during early zebrafish development to an environmentally relevant level (0.54 µg/L in water) and a concentration detected in the cord blood of FLX-treated pregnant women (54 µg/L in water). The FLX exposure reduced the stress response (arithmetic difference between the stress-induced and unstressed whole-body cortisol levels) in the adult female and male zebrafish, an effect that persisted for four generations. To model the possibility of a second antidepressant exposure, filial generation 4 was exposed to VEN (5 µg/L). We found that FLX exposure sensitized these descendants to VEN. VEN treatment further suppressed cortisol production in females and decreased spawning rates in adult pairs. This is an important demonstration that in an animal model, a brief ancestral exposure of great-great-grandparents to the selective serotonin reuptake inhibitor FLX will shape the physiological responses of future generations to the serotonin and norepinephrine reuptake inhibitor VEN.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Vera-Chang MN,Moon TW,Trudeau VL

doi

10.1210/en.2019-00281

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

2137-2142

issue

9

eissn

0013-7227

issn

1945-7170

pii

5531564

journal_volume

160

pub_type

杂志文章

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