Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, UNESP - Univ. Estadual Paulista, Botucatu, São Paulo State, Brazil.
School of Health Sciences, Federal University of Grande Dourados, UFGD, Dourados, Mato Grosso do Sul State, Brazil.
J Appl Toxicol. 2023 Mar;43(3):387-401. doi: 10.1002/jat.4389. Epub 2022 Sep 10.
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.
暴露于选择性 5-羟色胺再摄取抑制剂会影响激素依赖的过程,如大脑性分化。由于这些抗抑郁药在哺乳期的使用引起了关注,我们评估了文拉法辛对哺乳期暴露的可能影响及其对雄性大鼠生殖参数的后期影响。哺乳期大鼠从哺乳期第 1 天到第 20 天通过灌胃暴露于文拉法辛(3.85、7.7 或 15.4mg/kg/体重)。在所有接受治疗的母鼠的乳汁样本中都发现了文拉法辛和 O-去甲基文拉法辛残留,表明这种抗抑郁药会转移到后代的乳汁中。尽管母性行为正常,但分别用 7.7 和 15.4 处理的母鼠的尿素和尿酸水平升高,而 3.85 和 15.4 组的脾脏重量增加。中间剂量组雄性后代的玩耍行为参数减少。精子分析表明所有处理组的精子活力降低。下丘脑雄激素受体的表达在最高剂量组减少,尽管性行为没有受到影响。总之,文拉法辛通过母乳传递,并导致雄性后代的玩耍行为、精子质量和下丘脑雄激素受体(AR)含量发生变化,这可能表明大脑的不完全男性化。