Endocrine disrupting-chemicals (EDCs) are xenobiotic substances (or mixtures of substances) that interfere with any aspect of hormonal action and disrupt the homeostasis of the endocrine system of an intact organism, its progeny or a (sub)population (Zoeller et al., 2012; Demacopulo and Kreimann, 2019, Demeneix et al., 2020). Like other environmental pollutants, these substances can be found in water, food, soil, household objects, medical materials, cosmetics, among others. With the increase in the production of these chemicals and also chronic diseases, several authors describe that the effects of exposure on human and environmental health can be vast (Heindel et al., 2015). Still, due to the wide structural and chemical differences between these agents, it is difficult to describe the mechanism of action of each of them, which in turn makes it difficult to understand the effect on organisms (Pontelli et al., 2016). Among the EDCs, we can find tributyltin (TBT), an organoestanic compound, and bisphenol S (BPS), a compound used in plastic composition.

TBT is considered a persistent organic pollutant (POP) that can persist in marine sediments without the availability of oxygen for years, being able to biomagnify and bioaccumulate in organisms (Matthiessen and Gibbs, 2009; Barbosa et al., 2022). TBT is described in the literature as an agent that can induce damage in the uterus and ovaries of young adult rats (Podratz et al., 2012; Chen et al., 2020). A study demonstrated that tributyltin chloride (TBTCl) suppresses the uterine decidual cell response, and decreases progesterone serum levels, and these effects are responsible for early embryonic loss (Harazono and Ema, 2000). Recently, another study demonstrated that neonatal exposure to TBT leads to uterine dysplasia promoting changes in the uterine endometrium through increased fibrosis and epithelial thickness (Chen et al., 2020). Adult rats' exposure to organotins (OTs) in contaminated seafood promote ovary irregular estrous cycle irregularity, abnormal follicular development, and increase of interstitial collagen deposition (Podratz et al., 2015).

Following restrictions and regulations on the use and exposure to Bisphenol A (BPA), manufacturers have replaced it with related compounds, including BPS, in the production of plastic-based materials (Liao et al., 2012a). In the literature, there are studies stating that BPS is also an EDC and has carcinogenic potential (Žalmanová et al., 2016; Ullah et al., 2018). High concentrations of BPS have been detected in human urine (Liao et al., 2012b). BPS exposure in mice causes alterations in the expression of genes regulated by estrogen, which causes premature follicular development (Hill et al., 2017). This discovery emphasizes the need for more investigation on the potential risks associated with BPS exposure.

Although these chemicals have distinct applications, TBT and BPS are often found together in contaminated samples, suggesting concurrent exposure to these EDCs. BPS and TBT have been detected in agricultural soils, raising the potential for contamination of crops grown in these areas (Stéphane et al., 2008; Yihao et al., 2023). They are also present in sediments, river water, and marine environments (Qi et al., 2022; Peng et al., 2023). Additionally, these compounds have been identified in animal tissues, such as some fish species (Hugo et al., 2021; Cao et al., 2024) suggesting that consumption of contaminated biota may lead to human exposure and potential combined effects that remain unknown.

This study aims to assess the effects of subacute exposure to TBT, BPS, and their combination on the morphology of the ovary and uterus, as well as on the HPG axis in adult female Wistar rats.