Non-steroidal anti-inflammatory drugs (NSAIDs) in pregnancy and lactation: effects on the hypothalamic sexual differentiation process in male rats

• Grant number: 25/02352-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Arielle Cristina Arena
• Grantee: Luara Magalhães
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used class of medication for the treatment of pain, fever and inflammation, being regularly administered even to pregnant and lactating women. These drugs have an inhibitory effect on the Cyclooxygenase enzyme (COX-1 and COX-2), leading to a reduction in PGE2. Additionally, NSAIDs can act as endocrine disruptors. Studies have demonstrated the importance of PGE2 in the development of the nervous system, especially in the process of hypothalamic sexual differentiation (HSD), as well as the adverse impacts of endocrine disruptors on this process. Considering that NSAIDs can cross the placental membrane and cause adverse effects on fetal development, the use of anti-inflammatory drugs during pregnancy becomes a concern. Therefore, the objective of this study is to evaluate the effects resulting from gestational and lactational exposure to NSAIDs on the sexual behaviour and fertility of male rats in adulthood. To this end, pregnant rats will be distributed into four experimental groups and subjected to different oral treatments (gavage): 1. Control Group (1 mL/kg - water); 2. Acetaminophen Group (Paracetamol, 125 mg/kg); 3. Acetylsalicylic Acid (ASA) Group (6 mg/kg) and 4. Nimesulide Group ( 11 mg/kg) The chosen dosages were based on the therapeutic doses and converted to the animal dose concerning the rats' body surface area. The treatment will occur from gestational day 15 until the end of the lactational period (lactational day 22), a critical period for HSD in males. After the end of the treatment, the male offspring will be evaluated through the following parameters: sexual behaviour and sexual preference, fertility test, as well as sperm and hematological analysis.