AUTHOR=Sheftel Celeste M. , Liu Lihe , Field Sena L. , Weaver Samantha R. , Vezina Chad M. , Peñagaricano Francisco , Hernandez Laura L. 

TITLE=Impact of Fluoxetine Treatment and Folic Acid Supplementation on the Mammary Gland Transcriptome During Peak Lactation

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.828735

DOI=10.3389/fphar.2022.828735

ISSN=1663-9812

ABSTRACT=Serotonin is a key regulator of mammary gland homeostasis during lactation. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat peripartum depression, but also modulates mammary gland serotonin concentrations and signaling in part through DNA methylation. The objective of this study was to determine mouse mammary transcriptome changes in response to the SSRI fluoxetine and how methyl donor supplementation, achieved by folic acid supplementation, affected the transcriptome. Fluoxetine treatment altered fifty-six genes. Elovl6 was the most significantly altered gene by fluoxetine treatment along with gene pathways such as fatty acid homeostasis, PPARγ, and adipogenesis, which are critical for milk fat synthesis. Further, impacted genes and gene-sets in the mammary gland included serotonin and dopamine metabolism, calcium trafficking, lipid metabolism, and immune function. Folic acid supplementation impacted pathways involving transcriptional regulation, glucose metabolism and milk protein synthesis, which are critical for successful lactation. In conclusion, peripartal SSRI use and folic acid supplementation altered critical genes related to milk synthesis and mammary gland function that are important to a successful lactation. However, folic acid supplementation did not reverse changes in the mammary gland transcriptome altered by peripartal SSRI treatment.