Transgenerational effect of parental obesity and chronic parental bisphenol A exposure on hormonal profile and reproductive organs of preadolescent Wistar rats of F1 generation: A one-generation study

Abstract

There is a global concern about adverse health effects of endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA), an estrogenic and obesogenic compound, used in the plastic and medical industry has a dominant position among EDCs as far as human health and regulatory scenario are concerned. Due to its omnipresence across the biosphere, population of all age groups and health status is unavoidably exposed to BPA. Transgenerational exposure to BPA and its effects have also been recognized. However, there is no report on the transgenerational effect of BPA on metabolically disordered parents, such as obese ones. We studied effect of BPA exposure in F0 generation and its impact on F1 generation and factored parental obesity in transgenerational effect of concurrent exposure to low dose BPA (10 ppm × 180 days) in Wistar rats in a one-generation study protocol. The exposed F0 generation animals were crossed and F1 generation was analyzed 35 days after birth for indications of reproductive toxicity. We observed changes in hormone levels and disturbance in glucose and lipid homeostasis. Animals showed increased serum cholesterol and triglycerides along with higher birth weight and rapid weight gain. Histopathological evidence confirmed the presence of regressive and inflammatory changes in the ovary and testis. The test group showed metabolic disturbances in comparison to control group. Our study showed the additive effect of parental obesity in transgenerational reproductive toxicity of BPA. Female animals of F1 generation of BPA-treated obese parents showed more insulin resistance than males with similar exposure scenario. Our study highlights the confounding role of metabolic disorders such as obesity in the transgenerational toxicity of BPA, which otherwise itself is implicated in the aetiology of such metabolic disorders, directly or indirectly.

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

“…Tail impairment, sperm hook curvature, poor sperm morphology, follicle cell loss in the primordial, and cell loss in the stroma are just a few examples of data supporting this claim. This type of anomaly can be handed on through the F1 lineages [ 16 ]. This is because BPA has the ability to induce obesity to be passed down through the generations through epigenetic transgenerational inheritance.…”

“…Since glucose metabolism plays a vital role in spermatogenesis, impaired glucose tolerance greatly affects the normal function and structure of the sperm. In female subjects, stromal cell loss due to the increased level of oxidative stress, and the decreased level of SOD, GSH, or GPx may further enhance the transmission of the defects through reproductive organs [16]. Another study shows that BPA exposure in prenatal interferes with miRNA expression, causing 15 related genes to insulin signaling to be affected.…”

Role of Bisphenol A in Regulation of Arrival of Sexual Maturity and Fertility in Male Albino Rats

“…It reveals that there is a probability of loss in relatedness between body weight and testicular weight, nonetheless, its chances are highly unlikely at this particular dose. Various earlier studies have noted increase in body weight while reduction in testicular weight following low dose exposure of BPA [34,35,36,37]. Thus, it is possible to assume an inverse proportionality between body and testicular weight.…”

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

“…They concluded that, with their experimental range of BPA, the higher the dose to which the animals are exposed perinatally, the earlier its effect on glucose metabolism in the offspring. Dabeeret et al [68] studied the effects of exposure to low doses of BPA (10 ppmx180 days) in the F0 generation of obese Wistar rats and its impact on the F1 generation, analyzing it on day 35 post-birth. It was observed that there were no differences in the serum glucose patterns of the F1 exposed in relation to the control, which would reveal the compensatory capacity of the organism, in which the glucose levels returned to the normal ranges of the species, although it would be interesting to elucidate if the tissue damage would be fully recovered.…”