Short and long-term effects of bisphenol S (BPS) exposure during pregnancy and lactation on plasma lipids, hormones, and behavior in rats

Silva, Beatriz Souza da; Pietrobon, Carla Bruna; Bertasso, Iala Milene; Lopes, Bruna Pereira; Carvalho, Janaíne Cavalcanti; Peixoto-Silva, Nayara; Santos, Tatianne Rosa dos; Claudio-Neto, S.; Manhães, Alex C.; Oliveira, Elaine de; Moura, Egberto Gaspar de; Lisboa, Patrícia Cristina

doi:10.1016/j.envpol.2019.03.100

Cited by 51 publications

(26 citation statements)

References 58 publications

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“…Regarding progesterone, previous studies have shown a lower level of progesterone in the circulating plasma of rats exposed to BPS ( 43 ). This is relevant to the decrease in plasma progesterone observed in restricted ewes after BPS exposure.…”

Section: Discussionmentioning

confidence: 94%

Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status

et al. 2022

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Bisphenol A (BPA), a plasticizer and endocrine disruptor, has been substituted by bisphenol S (BPS), a structural analogue that had already shown adverse effects on granulosa cell steroidogenesis. The objective of this study was to assess the effect of chronic exposure to BPS, a possible endocrine disruptor, on steroid hormones in the ovary, oviduct and plasma using the ewe as a model. Given the interaction between steroidogenesis and the metabolic status, the BPS effect was tested according to two diet groups. Eighty adult ewes were allotted to restricted (R) and well-fed (WF) groups, that were further subdivided into two subgroups. Ewes were exposed to 50 µg BPS/kg/day in their diet (R50 and WF50 groups) or were unexposed controls (R0 and WF0 groups). After at least 3 months of BPS exposure, preovulatory follicular fluid, oviduct fluid and plasma were collected and steroid hormones were analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). A deleterious effect of restricted diet on the volume of oviduct fluid and numbers of pre-ovulatory follicles was observed. Exposure to BPS impaired estradiol concentrations in both follicular and oviduct fluids of well-fed ewes and progesterone, estradiol and estrone concentrations in plasma of restricted ewes. In addition, a significant interaction between metabolic status and BPS exposure was observed for seven steroids, including estradiol. In conclusion, BPS acts in ewes as an endocrine disruptor with differential actions according to metabolic status.

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Section: Discussionmentioning

confidence: 94%

Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status

et al. 2022

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“…Although we cannot be sure, it seems likely that the effects noted (e.g., on neurotransmitter levels) persist until parturition, and it does not seem unreasonable to infer that these changes directly influence fetal brain development, possibly leading to permanent neurobehavioral effects. We and others have shown that developmental exposure of fetuses in various rodent models to BPA/BPS can alter later neurobehavioral responses (76,80,81,(83)(84)(85)(86)(87). To tease apart potential BPA/BPS-induced effects through the placental-brain axis vs. direct effects on the fetal brain, it may be necessary to create conditional knockout mice that lack BPA/BPS-responsive genes in the GCs and spongiotrophoblast.…”

Section: Discussionmentioning

confidence: 99%

Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta–brain axis

Mao

Jain

Denslow

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

102

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Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to trophoblast giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, a negative correlation existed between dopamine+GCs and reductions in spongiotrophoblast to GC area ratio. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GCs within the junctional zone. Third, imbalances in neurotransmitter-positive GCs and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental–brain axis of the developing mouse fetus.

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“…In contrast, while temephos produced permanent damage in metabolically competent HepG2 cells, reversible DNA damage was observed in human lymphocytes, which have a very low metabolic activity . The formation of BPS from the temephos biotransformation also suggests possible reproductive effects, since this compound is classified as an endocrine disruptor on the basis of its properties as an estrogen receptor agonist. , Thus, the temephos biotransformation may generate several metabolites, all of which have a wide range of toxicity. To date, it is difficult to propose which temephos metabolites are responsible for certain effects because of the lack of metabolic pathway information in different species, including humans.…”

Section: Discussionmentioning

confidence: 99%

Human Biotransformation Pathway of Temephos Using an In Silico Approach

Reyes-Chaparro

Verdín-Betancourt

Sierra-Santoyo

2020

Chem. Res. Toxicol.

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Temephos is an organophosphorothioate (OPT) larvicide used for controlling vectors of diseases such as dengue, chikungunya, and Zika. OPTs require a metabolic activation mediated by cytochrome P540 (CYP) to cause toxic effects, such as acetylcholinesterase (AChE) activity inhibition. There is no information about temephos biotransformation in humans, and it is considered to have low toxicity in mammals. Recent studies have reported that temephos-oxidized derivatives cause AChE inhibition. The aim of this study was to propose the human biotransformation pathway of temephos using in silico tools. The metabolic pathway was proposed using the MetaUltra program of MultiCase software as well as the Way2Drug and Xenosite web servers. The results show the following three essential reactions of phase I metabolism: (1) S-oxidation, (2) oxidative desulfurization, and (3) dephosphorylation, as well as the formation of 19 possible intermediary metabolites. Temephos dephosphorylation is the most likely reaction, and it enables phase II metabolism for glucuronidation to be excreted. However, the CYP-dependent metabolism showed that temephos oxon can be formed, which could lead to toxic effects in mammals. CYP2B6, 2C9, and 2C19 are the main isoforms involved in temephos metabolism, and CYP3A4 and 2D6 have minor contributions. According to computational predictions, the highest probability of temephos metabolism is dephosphorylation and phase II reactions that do not produce cholinergic toxic effects; nonetheless, the participation of CYPs is highly possible if the primary reaction is depleted.

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Short and long-term effects of bisphenol S (BPS) exposure during pregnancy and lactation on plasma lipids, hormones, and behavior in rats

Cited by 51 publications

References 58 publications

Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status

Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status

Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta–brain axis

Human Biotransformation Pathway of Temephos Using an In Silico Approach

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