Sodium benzoate exposure from juvenile to peripubertal period disrupts HPG-axis in both male and female rats.

Abstract

Sodium benzoate (SB) is a synthetic preservative that is widely used in the food and pharmaceutical industries. Despite its antibacterial and fungal static properties, it can impair reproduction. However, its toxicity has not been fully studied during the sensitive developmental period in mammals. This study was aimed at examining the adverse effects of SB during the developmental period, particularly the HPG-axis. Thirty male and 30 female weanling rats (PND 21) were administered oral doses of SB (10-1000 mg/kg/BW) until the peripubertal period, whereas control animals were administered only distilled water. Body weight, reproductive organ weight, oxidants, antioxidants, and reproductive hormones were measured. Kisspeptin (hypothalamic peptide) regulates the HPG-axis by activating GnRH secretion and was assessed by immunohistochemistry using specific primary and secondary antibodies. Morphometric and histopathological analyses were performed on hematoxylin- and eosin-stained sections to assess reproductive organ damage. The experimental groups showed a significant reduction in body as well as reproductive organ weight. Higher reactive oxygen species (ROS) and TBARS levels were observed, accompanied by reduced antioxidant enzyme activities, such as SOD, POD, CAT, and GSH in the treatment groups. Furthermore, a hormonal analysis revealed a dose-dependent decrease in estradiol, testosterone, and FSH levels, whereas an increase in LH was noted in animals that were administered SB. A dose-dependent decrease in kisspeptin expression was observed in male and female treatment groups. Morphometric analysis revealed a significant decrease in the ovarian and testicular volumes. In addition, apparent cytoarchitectural alterations in both the testis and ovary were noticed, signifying profound structural damage to the gonadal tissue because of SB exposure. Our findings suggest that developmental exposure to SB causes serious structural and molecular changes in the HPG axis. These abnormalities over the critical developmental window may lead to disruption in the maturation of the reproductive system, which could be attributed to compromised reproductive health in adults.

Supplementary information: The online version contains supplementary material available at 10.1007/s43188-025-00286-z.