PUBLICATION
Serotonin Reuptake Inhibitor Citalopram Inhibits GnRH synthesis and Spermatogenesis in the Male Zebrafish
- Authors
- Prasad, P., Ogawa, S., Parhar, I.S.
- ID
- ZDB-PUB-150711-7
- Date
- 2015
- Source
- Biology of reproduction 93(4): 102 (Journal)
- Registered Authors
- Ogawa, Satoshi
- Keywords
- Fish reproduction, Gonadotropin-releasing hormone (GnRH / GnRH receptor), Male infertility, Serotonin, Spermatogenesis
- MeSH Terms
-
- Animals
- Citalopram/pharmacology*
- Dose-Response Relationship, Drug
- Gene Expression Regulation, Developmental/drug effects
- Gonadotropin-Releasing Hormone/biosynthesis*
- Gonadotropin-Releasing Hormone/genetics
- Infertility, Male/chemically induced
- Male
- Neurons/drug effects
- Pyrrolidonecarboxylic Acid/analogs & derivatives
- Receptors, Serotonin/biosynthesis
- Selective Serotonin Reuptake Inhibitors/pharmacology*
- Serotonin/metabolism
- Spermatogenesis/drug effects*
- Testis/cytology
- Testis/drug effects
- Testis/metabolism
- Zebrafish*
- PubMed
- 26157069 Full text @ Biol. Reprod.
Citation
Prasad, P., Ogawa, S., Parhar, I.S. (2015) Serotonin Reuptake Inhibitor Citalopram Inhibits GnRH synthesis and Spermatogenesis in the Male Zebrafish. Biology of reproduction. 93(4):102.
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants for the treatment of depression. However, SSRIs cause sexual side effects such as anorgasmia, erectile dysfunction and diminished libido which are thought to be mediated through the serotonin (5-hydroxytryptamine, 5-HT) system. In vertebrates, gonadotropin-releasing hormone (GnRH) neurons play an important role in the control of reproduction. To elucidate the neuroendocrine mechanisms of SSRI induced reproductive failure, we examined the neuronal association between 5-HT and GnRH (GnRH2 and GnRH3) systems in the male zebrafish. Double-label immunofluorescence and confocal laser microscopy followed by 3D construction analysis showed close associations between 5-HT fibers with GnRH3 fibers and preoptic-GnRH3 cell bodies but there was no association with GnRH2 cell bodies and fibers. Quantitative real-time PCR showed that short term treatment (two weeks) with low-medium doses (4μg/L and 40μg/L) of citalopram significantly decreased mRNA levels of gnrh3, gonadotropins (lhb and fshb) and 5-HT related genes (tph2 and sert) in the male zebrafish. In addition, short term citalopram treatment significantly decreased the fluorescence density of 5-HT and GnRH3 fibers compared with controls. Short term citalopram treatment with low, medium, and high dose (100μg/L) had no effects on the profiles of different stages of spermatogenesis, while long term (one month) citalopram treatment with medium and high doses significantly inhibited the different stages of spermatogenesis. These results show morphological and functional associations between the 5-HT and the hypophysiotropic GnHR3 system, which involve SSRI-induced reproductive failures.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping