title: Developmental fluoxetine exposure and prenatal stress alter sexual differentiation of the brain and reproductive behavior in male rat offspring.
abstract: Depression during pregnancy and postpartum is a significant health problem and affects up to 20% of women. While selective serotonin reuptake inhibitor (SSRI) medications are the drug of choice for treatment of maternal depression, the combined effect of maternal depression and perinatal SSRI exposure on offspring development is poorly investigated. Our aim was to determine the role of exposure to fluoxetine during development on sexual behavior and sexually dimorphic brain structures in male offspring using a rodent model of maternal adversity. Sprague-Dawley rat dams were stressed during gestation and were chronically treated throughout lactation with either fluoxetine or vehicle beginning on postnatal day 1. Four groups of offspring were used: (1) Control+Vehicle, (2) Control+Fluoxetine, (3) Prenatal Stress+Vehicle, and (4) Prenatal Stress+Fluoxetine. We show here that developmental fluoxetine treatment decreases the anogenital distance in juvenile male offspring. In adult male offspring, maternal fluoxetine treatment results in a decrease in the number of intromissions, a longer latency to the first intromission, and a longer latency to the first ejaculation. Furthermore, developmental fluoxetine and/or prenatal stress decrease the area of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Prenatal stress, but not exposure to developmental fluoxetine, decreases the number of tyrosine hydroxylase (TH)-positive cells in anteroventral periventricular nucleus (AVPv) and the volume of the posterior bed nucleus of the stria terminalis (pBST) in male offspring. These results provide important evidence for the long-term impact of maternal adversity and maternal fluoxetine use on the development of primary endocrinology systems in juvenile and adult male offspring.
authors: School for Mental Health and Neuroscience, Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors: Ine
authors: I
authors: Rayen
authors: Harry W M
authors: HW
authors: Steinbusch
authors: Thierry D
authors: TD
authors: Charlier
authors: Jodi L
authors: JL
authors: Pawluski
mesh_terms: D001003:Anal Canal / Q000196:embryology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology*; D004542:Ejaculation / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000633:toxicity*; D005837:Genitalia, Male / Q000196:embryology; D008297:Male; D020644:Midline Thalamic Nuclei / Q000737:chemistry / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009929:Organ Size; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D011297:Prenatal Exposure Delayed Effects; D011301:Preoptic Area / Q000196:embryology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000737:chemistry / Q000196:embryology / Q000648:ultrastructure; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000633:toxicity*; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology; D013739:Testosterone / Q000097:blood; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D004958:Estradiol; D005473:Fluoxetine; D009419:Nerve Tissue Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013739:Testosterone; D014446:Tyrosine 3-Monooxygenase
keywords: Antidepressant medication; Depression; Development; Hypothalamus; Maternal depression; Prenatal stress; Reproduction; SSRI; Sexual differentiation