4.5 Article

Lactational exposure to venlafaxine provokes late repercussions on reproductive parameters in male rat offspring

Journal

JOURNAL OF APPLIED TOXICOLOGY
Volume 43, Issue 3, Pages 387-401

Publisher

WILEY
DOI: 10.1002/jat.4389

Keywords

brain sexual differentiation; maternal milk; postpartum depression; serotonin; sexual behavior

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Exposure to venlafaxine during lactation can lead to changes in play behavior, sperm quality, and hypothalamic androgen receptor content in male offspring. This study highlights the importance of evaluating the potential effects of antidepressant use during lactation.
Exposure to selective serotonin reuptake inhibitors can affect hormone-dependent processes, such as the brain sexual differentiation. Because the use of these antidepressants cause concern during lactation, we evaluated the possible effects of venlafaxine on lactational exposure and its late repercussions on reproductive parameters in male rats. Lactating rats were exposed to venlafaxine (3.85, 7.7, or 15.4 mg/kg/body weight; gavage), from lactational day 1 to 20. Venlafaxine and O-desmethylvenlafaxine residues were found in all milk samples of dams treated, demonstrating the lactational transfer of this antidepressant to the offspring. Although the maternal behavior was normal, the dams presented an increase in urea and uric acid levels in the groups treated with 7.7 and 15.4, respectively, as well as a spleen weight increased in the 3.85 and 15.4 groups. The male offspring showed a decrease in play behavior parameters in the intermediate dose group. Sperm analysis indicated a reduction in sperm motility in all treated groups. The androgen receptor expression in the hypothalamus was decreased in the highest dose group, although the sexual behavior had not been affected. In conclusion, venlafaxine was transferred through breast milk and promoted changes in play behavior, sperm quality, and hypothalamic androgen receptor (AR) content, which may indicate an incomplete masculinization of the brain of male offspring.

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