Exposure to sodium saccharin, DOHaD and its implications on the testis

Abstract

Infertility, characterized by the inability to conceive after a year of unprotected sexual intercourse, may be linked to problems in spermatogenesis, a process regulated by hormones and influenced by external factors during pregnancy. The DOHaD theory suggests that exposure to external agents during pregnancy, such as maternal diet, can affect the offspring's health profile. In this context, it is important to note that sodium saccharin, a non-nutritive sweetener, is frequently included in maternal diet. Although sodium saccharin is approved by the FDA, its consumption can compromise testicular development and sperm quality in offspring, raising concerns about reproductive health and infertility. Therefore, the objective of this study is to verify the intergenerational effects on male rats (F1 and F2 generations) caused by exposure to sodium saccharin during the gestational, lactational, pubertal, and adult phases, focusing on the testicular functional and morphological profile. Sprague-Dawley rats will be divided into two experimental groups: Control Group (C), consisting of rats that consume food and water ad libitum (n=10); and Sodium Saccharin Group (S), consisting of rats that consume food and water ad libitum sweetened with 0.3% sodium saccharin (n=10). The male and female offspring of the F0 generation rats will constitute the F1 generation. From postnatal day (PND) 55 to PND 120, male offspring will receive the same diet provided to the maternal group. At PND 90, males treated with saccharin will be mated (non-inbred matings) with females from group C to obtain the F2 generation. The animals will be killed at PND 120. The care and procedures for the F2 profile will be the same as those applied to the F1 profile. At 120 days of age, the male offspring of F1 and F2 will be killed, and the testes and epididymis will be processed according to histological, immunohistochemical, and oxidative stress study protocols.