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Influence of lactational exposure to the antidepressant venlafaxine: late repercussion on reproductive and behavioral parameters in male rats.

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Suyane Da Silva Moreira
Total Authors: 1
Document type: Master's Dissertation
Press: Botucatu. 2021-09-09.
Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
Defense date:
Advisor: Arielle Cristina Arena

The global prevalence of postpartum depression is estimated at 100-150 cases per 1000 births, and one of the most suitable drugs for treatment is venlafaxine, a serotonin and noradrenaline reuptake inhibitor (IRSN). As serotonin plays a key role in brain development, studies show that prenatal and postnatal exposure to IRSNs can alter the hypothalamic-pituitary-adrenal (HHA) and hypothalamic-pituitary-gonadal (HHG) axes and hormone-dependent processes, such as the hypothalamic sexual differentiation. Due to the importance of testosterone in the hypothalamic sexual differentiation process, the use of antidepressants during pregnancy and lactation is of concern. Thus, the objective of this study is to evaluate the possible effects of lactational exposure to venlafaxine and its late repercussions on reproductive parameters in male rats. Therefore, lactating rats were exposed to three doses of venlafaxine (3.85, 7.7 or 15.4 mg / kg), via gavage, from the 1st day to the 20th day after delivery. On the 5th day of lactation, the females were subjected to maternal behavior assessment, and at the end of the exposure period, the rats were euthanized and blood and organs were collected for further evaluation. After birth, male puppies were assessed using the following parameters: determination of body weight, anogenital distance, ages of preputial separation, testicular descent and play behavior. In adult life, these same animals were investigated in relation to reproductive organ weights, sperm count, sperm morphology and motility, fertility test, male sexual behavior, the presence of female sexual behavior and sexual preference, blood was collected for hormonal dosage and the hypothalamus was collected for analysis of androgen receptor expression by western blotting. In relation to the females evaluated, there was an increase in spleen weight and an increase in serum urea and uric acid levels, moreover there was no change in maternal behavior. The analysis of the initial development showed an increase in the body weight of the offspring of the lowest dose group on the 13th postnatal day, but this difference was normalized on the 22nd. Still in relation to offspring, a decrease in play behavior parameters was observed in the intermediate dose group and an increase in seminal vesicle weight in the same group. Sperm analyzes indicated a reduction in the number of progressive sperm in all experimental groups, in addition to an increase in the number of mobile sperm in the group with the highest dose. There was also a decrease in the masculinization index in the infertility test, and in relation to the behavior and sexual preference tests there were no statistical changes between the groups, however, a reduction in the expression of androgen receptors on the hypothalamus was detected in the higher dose group. It is concluded that exposure to Venlafaxine was slightly toxic to lactating rats and detrimental to the cognitive development of male offspring, in addition to causing relevant sperm changes, despite not compromising sexual behavioral parameters in adulthood. Further studies are needed to better understand the role of Venlafaxine in the development of sperm and in the hypothalamic sexual differentiation process. (AU)

FAPESP's process: 19/02902-8 - Influence of lactational exposure to venlafaxine antidepressant: late repercussion on reproductive and behavioral parameters, in male rats
Grantee:Suyane da Silva Moreira
Support type: Scholarships in Brazil - Master