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Influence of in utero and/or lactational exposure to the antidepressant venlafaxine: repercussion on reproductive and behavioral parameters in male rats

Grant number: 22/03569-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2023
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Principal Investigator:Arielle Cristina Arena
Grantee:Beatriz de Matos Manoel
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):23/08574-8 - Impact of neonatal cell-specific silencing of AR, MAGL or DAGL on adolescent play., BE.EP.DR


Clinical depression is a common disorder observed in women of childbearing age, especially during pregnancy and postpartum. Venlafaxine, classified as a Serotonin and Norepinephrine Reuptake Inhibitor (SNRI), is one of the main options for the treatment of prenatal and postnatal depression. Since serotonin has an important role in the development of the central nervous system, in utero and lactational exposure to SNRIs can affect hormone-dependent processes, such as the hypothalamic sexual differentiation. In this sense, our research group observed that lactational exposure to venlafaxine compromised sperm and behavioral parameters and, possibly, masculinization of the hypothalamus, in addition to demonstrating the presence of venlafaxine and its active metabolite in breast milk. Additional data comparing exposure to this drug at different critical periods of development are needed. Therefore, the aim of this study is to evaluate the effects resulting from maternal exposure during pregnancy and/or lactation to the antidepressant venlafaxine on sexual development and the possible late repercussions on reproductive and behavioral parameters in male rats. Female Wistar rats will be treated daily, via gavage, with distilled water or venlafaxine (4.5 mg/kg/day) during pregnancy and lactation (CPL and VENPL) or only during lactation (CL and VENL). On the 5th day of lactation, the females will be subjected to maternal behavior assessment. The male offspring will be evaluated at different ages (21, 50 and 90 postnatal days), according to the following parameters: evaluation of sexual development, play behavior, fertility test, sexual behaviors, quantification of SDN-POA volume, organs weight, hormonal dosage, histomorphometric analysis, immunohistochemistry of the epididymis, testis gene expression, evaluation of sperm parameters and vas deferens contractility. This study, in addition to providing an opportunity to create qualified human resources, will obtain important information for the implementation of government public health policies aimed at greater control of the use of this class of drugs during pregnancy and breastfeeding.

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