The effects of perinatal bisphenol A exposure on thyroid hormone homeostasis and glucose metabolism in the prefrontal cortex and hippocampus of rats

Abstract

Introduction Bisphenol A (BPA) is an endocrine disruptor widely used to manufacture consumer goods. Although the thyroid hormone (TH) disrupting potential of BPA has been thought to be responsible for the neuropsychiatric deficits in the animals that experienced perinatal BPA exposure, the TH availability change at the level of specific brain structures has not been subject to systematic investigation. Methods In the present study the impacts of perinatal BPA exposure (0.1 mg/L in drinking water) spanning gestation and lactation on TH homeostasis in the prefrontal cortex (PFC) and hippocampus were assessed in male Sprague–Dawley rats at postnatal day 21 (PND21) and PND90. As TH regulates brain glucose metabolism at multiple levels，the effects of BPA treatment on glucose metabolism in the brain tissues were also assessed in adult rats. Results The results showed heterogeneous changes in TH concentration induced by BPA between serum and brain tissues, additionally, in the BPA–treated pups, up–regulated expression of the TH transporter monocarboxylate 8 mRNA at PND21 and increased type 3 iodothyronine deiodinase mRNA expressions at PND21 and PND90 were observed. Meanwhile, decreased glucose metabolism was seen in the PFC and hippocampus, while deficits in locomotor activity, spatial memory and social behaviors occurred in BPA‐treated groups. Conclusion These data support the concept that the developing brain possesses potent mechanisms to compensate for a small reduction in serum TH, such as serum hypothyrodism induced by BPA exposure, however, the long‐term negative effect of BPA treatment on TH homeostasis and glucose metabolism may be attributable to neuropsychiatric deficits after mature.

Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

“…Two studies have investigated the relationship of BPA exposure with thyroid function (Table 3). Viguié et al [122] reported that BPA exposure of pregnant ewes was associated with a transitory hypothyroxinemia of both mothers and their newborn lambs, with a significant reduction of both circulating total T4 (TT4) and free T4 (FT4), findings in agreement with rodent studies [111,112]. In a following study, the authors confirmed alterations of gestational thyroid function, observing a significant reduction of FT4 and total T3 (TT3), but not TT4, in pregnant ewes treated with environmentally-relevant BPA concentrations via subcutaneous and dietary routes of administration [123].…”

“…In other experiments, BPA exposure did not produce significant variations in plasma T4 levels [106][107][108][109] or, alternatively, the effects may not endure after BPA removal and metabolism [110][111][112]. It is still unclear whether exposure to BPA and its derivatives can cause hypothyroidism due to limited evidence.…”

“…The interactions between BPA and THs during pregnancy and fetal development have been recently studied. The association between BPA and TSH levels in newborns was stronger when the time elapsed between the two measurements was shorter [143,148], suggesting that specific windows of exposure may influence susceptibility to BPA or, alternatively, that a transient effect on the HPT axis may occur, as shown in rodents [111,112]. However, the inverse association of BPA-TSH in pregnant women detected through repeated measures as well as stratified analyses by visit could indicate the absence of a specific window of vulnerability [139].…”

Toxic Effects of the Mixture of Phthalates and Bisphenol A—Subacute Oral Toxicity Study in Wistar Rats

“…Moreover, recent interests are being directed to the effects of these substances on the thyroid tissue and thyroid hormone regulation, linking the changes in thyroid function with the consequential adverse reproductive health [35,36]. To investigate the effects of phthalates on the thyroid, in vivo rodent studies have been conducted to reveal the decrease in thyroid hormones after oral exposure to DEHP [35,37,38], DBP [39], and BPA [40,41]. This is in accordance with the human biomonitoring study from the national health and nutrition examination survey (NHANES, 2007(NHANES, -2008, which included 1346 adults (ages ≥20 years) and 329 adolescents (ages 12-19 years).…”

Toward a better understanding of the effects of endocrine disrupting compounds on health: Human-relevant case studies from sheep models

“…BPA is a good illustration on how a contaminant that does not seem to have any effect on the thyroid function of adult non-pregnant animals might affect this function in pregnant animals and/or their offspring. There are indeed data in both rodents and sheep showing that BPA can alter the thyroid function of pregnant animals and/or their offspring (Guignard et al, 2017;Silva et al, 2019;Viguié et al, 2013;Xu et al, 2019;Zoeller et al, 2005).…”