Analysis of Indirect Biomarkers of Effect after Exposure to Low Doses of Bisphenol A in a Study of Successive Generations of Mice

Abstract

Bisphenol A (BPA) is considered as being an emerging pollutant, to which both animal and human populations are continuously and inadvertently exposed. The identification of indirect biomarkers of effect could be a key factor in determining early adverse outcomes from exposure to low doses of BPA. Thus, this study on mice aims to evaluate and identify indirect biomarkers of effect through the analysis of their blood biochemistry, and of certain reproduction parameters after exposure to different BPA concentrations (0.5, 2, 4, 50, and 100 µg/kg BW/day) in drinking water over generations. Our results showed that there were no modifications in the reproductive parameters evaluated, like estrous cycle duration, litter size, or the percentage of the young alive at reaching the weaning stage, at the exposure levels evaluated. However, there were modifications in the biochemical parameters, e.g., alterations in the glucose levels, that increased significantly (p < 0.05) in the breeders at the higher exposure doses (50 and 100 µg/kg BW/day in F1; 50 µg/kg BW/day in F2 and 100 µg/kg BW/day in F3), that would suggest that the BPA could induce hyperglycemia and its complications in adult animals, probably due to some damage in the pancreas cells; albumin, that increased in the breeders exposed to the highest dose in F1 and F3, inferring possible hepatic alterations. Further, total proteins showed a diminution in their values in F1 and F2, except the group exposed to 100 µg/kg BW/day, whereas in F3 the values of this parameter increased with respect to the control group, this aspect likely being related to a possible hepatic and renal alteration. Based on these results, glucose, albumin, and total proteins could initially be considered as early indicators of indirect effect after prolonged exposure to low BPA doses over generations.

An Overview of the Health Effects of Bisphenol A from a One Health Perspective

“…Furthermore, some studies such as that of Cantonwine et al [72] and Weinberger et al [73] described an inverse correlation between the concentration of BPA in maternal urine and the length of gestation. However, the results of some research with animals indicate that, in females exposed to high concentrations of BPA, there was a lengthening of the gestation period, although this fact could not be directly attributed to exposure to BPA [11].…”

“…Exposure to BPA through different routes has demonstrated its impact on both human and animal health, describing effects on different systems and organic levels. Prominent effects described are (1) those on reproduction, (2) those on development, (3) transgenerational and multigenerational effects (4) those on the metabolism, (5) immunological effects, (6) those on the thyroid function, and (7) those on oxidative stress and inflammation, among others (Figure 1) [11,17,18].…”

“…One of the characteristics of endocrine disruptors, specifically BPA, is that they produce nonmonotonic dose-response curves (Figure 3). Example of nonmonotonic behavior dose-response curves (see [11,113,114]).…”

“…As a consequence of the enormous production of BPA, and the multiple uses of this compound, it is found everywhere in the environment and in food, with both the human and the animal populations being continuously and inadvertently exposed to this endocrine disruptor. Due to its significant effects on health, attempts have been made to find alternatives to its use, although there is currently no safe option for this compound, despite a large number of studies focusing on the search for safe exposure levels [10][11][12]. BPA is considered to be an "emerging pollutant" to which we are constantly being exposed, and the environment, animals, and people can be affected by its possible harmful effects [13,14].…”

Bisphenol A (BPA) Leading to Obesity and Cardiovascular Complications: A Compilation of Current In Vivo Study

“…For instance, extreme levels of cortisol are indicative of interference of BPA in the hypothalamic–pituitary–adrenal axis, while AST, ALT, and lactate dehydrogenase are indicators for liver damage in an attempt to remove BPA metabolites [ 130 ]. Different biomarkers than the abovementioned biomarkers serve as an ideal diagnostic tool if the subjects refer to hospitals with any underlying conditions such as subjects exposed with BPA with ovarian cancer; the presence of keratin 4 genes is vital to confirm the diagnosis [ 130 ]. However, visfatin, resistin, leptin, or haptoglobin are ideal biomarkers for adiposity.…”