Maternal exposure of rats to sodium saccharin during gestation and lactation in rats: intergerational study

• Grant number: 23/05096-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Patricia Fernanda Felipe Pinheiro
• Grantee: Patricia Fernanda Felipe Pinheiro
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Alana Rezende Godoi ; Francisco Eduardo Martinez ; Vanessa Caroline Fioravante

Abstract

Intergenerational inheritance can be determined by changes in the germ cell lineage. The hypothesis of the "developmental origins of health and disease" (DOHaD) indicates that changes in the intrauterine environment can affect the reproductive development of offspring. Environmental and nutritional factors can interfere in the maternal organism causing important changes that reflect on the reproductive capacity of the offspring. In this sense, sweeteners are nutritional additives that can be consumed during pregnancy and lactation. Among the sweeteners consumed, it is important to highlight that sodium saccharin is the most consumed worldwide, being permeable to the placenta and may be present in breast milk. A study conducted in our laboratory showed that maternal exposure to sodium saccharin during gestation and lactation periods directly affected spermatogenesis in male offspring (published data), and also demonstrated an increase in antioxidant enzymes in the testes (unpublished). Thus, this work aims to verify the possible inheritance in the programming of intergenerational development of male rats (F1 and F2) caused by the use of sodium saccharin in rats (F0) exposed during gestation and lactation. Pregnant Sprague-Dawley rats divided into two experimental groups will be used: Control Group (C): composed of rats that will consume feed and water ad libitum (n=10); Sodium saccharin Group (S): composed of rats that will consume feed and water ad libitum sweetened with 0.3% sodium saccharin (n=10). Male offspring (21 and 120 days old) will be killed and testes, epididymides, and cardiac, visceral, retroperitoneal, and epididymal fat will be dissected and weighed. The testes will be processed according to the protocols for histological, immunohistochemical, and Western Blotting studies (Ki67, AR, ER-±, cytochrome p450, 5-± reductase, T2R3). Tissue concentrations of steroid hormones, oxidative stress, morphology, motility, daily production, count, sperm transit time, and protein expression by mass spectrometry will also be analyzed. (AU)