Bisphenol-A Exposure Induced Neurotoxicity and Synapse and Cytoskeleton Dysfunction in Neuro-2a Cells

Bisphenol A (BPA) is one of the typical environmental endocrine disruptors. BPA was leached from polycarbonate containers into food and water, and it has been detected in collective samples from humans. Microtubule-associated protein 2 (MAP2) and Tau maintain microtubule normal function and promote the normal development of the nervous system. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic plasticity. This study aimed to determine the adverse effects of BPA on Neuro-2a cells by investigating the synaptic and cytoskeletal damage. Cells were exposed to 0 (Minimum Essential Medium, MEM), 0.01% (v/v) DMSO and 150 µM BPA for 12, 24, or 36 h. Morphological analysis revealed that the cells in the BPA-treated groups shrank, collapsed, and had a reduced number of synapses compared with those in the control groups. CCK-8 and LDH assays showed that the mortality of Neuro-2a cells increased as the BPA treatment time was prolonged. Transmission electron microscopic analysis further revealed that cells demonstrated nucleolar swelling and nuclear membrane and partial mitochondrial dissolution or condensation following BPA exposure. BPA also significantly decreased the relative protein expression levels of MAP2, Tau, and Dbn (P < 0.01). Interestingly, the relative protein expression levels of SYP increased (P < 0.01). These results indicated that BPA damaged the development and proliferation of Neuro-2a cells by disrupting cytoskeleton and synaptic integrity.

PCB118 Induces Inflammation of Islet Beta Cells via Activating ROS-NLRP3 Inflammasome Signaling

Background. Diabetes mellitus is a clinical syndrome caused by genetic and environmental factors. Growing evidence suggests that exposure to environmental endocrine disruptors and activation of NLRP3 inflammasome signaling play a vital role in diabetes. However, it is unclear how PCB118, a common environmental endocrine disruptor, contributes to the incidence of diabetes, and its specific mechanism of action is unknown. In this study, we explored whether ROS-induced NLRP3 inflammasome priming and activation were related to PCB118 exposure in mouse islet β-TC-6 cells and the mechanisms of diabetes. Methods. Mouse islet β-TC-6 cells were cultured with PCB118 as a stimulating factor and ROS inhibitor N-acetyl cysteine (NAC) as an intervention. Cellular toxicity due to PCB118 was detected using the Cell Counting Kit-8; ROS was measured using DCFH-DA; the expressions of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β protein were detected by western blot; and IL-6, IL-18, and C-C chemokine ligand 2 (CCL-2) were measured by ELISA. Results. PCB118 caused significant toxicity to the cells when the stimulation concentration was equal to or greater than 80 nmol/L at 72 hours ( p < 0.05 ) and increased the levels of ROS, NLRP3, caspase-1, IL-1β, IL-6, IL-18, and CCL-2 ( p < 0.05 ); the expressions of procaspase-1 and pro-IL-1β were downregulated in a dose-dependent manner after PCB118 exposure ( p < 0.05 ), which was prevented by pretreatment with NAC ( p < 0.05 ). Conclusions. PCB118 can activate NLRP3 inflammasome signaling in islet beta cells via the oxidative stress pathway and cause inflammation in islet beta cells. It suggests that environmental endocrine disruptors play an important role in the inflammation of islet beta cells and may contribute to the development of diabetes through NLRP3 inflammatory signaling.

n-Butyl Benzyl Phthalate Exposure Promotes Lesion Survival in a Murine Endometriosis Model

Endometriosis is an inflammatory and estrogen-dependent gynecological disease associated with exposure to environmental endocrine disruptors. n-Butyl benzyl phthalate (BBP), a ubiquitous plasticizer, has weak estrogenic activity, and exposure to BBP is associated with endometriosis. We aimed to elucidate the immunomodulatory effect of BBP on endometriosis development. We previously established a surgery-induced endometriosis-like murine model. In the present study, we exposed those mice to BBP 10 days prior to surgery and 4 weeks after surgery at physiologically relevant doses to mimic human exposure. Chronic exposure to BBP did not promote the growth of endometriotic lesions; however, the lesion survival rate in BBP-treated mice did increase significantly compared with control mice. Multiparametric flow cytometry showed that BBP exposure did not affect the homeostasis of infiltrated immune subsets in lesions but did enhance CD44 (adhesion marker) expression on plasmacytoid dendritic cells (pDCs). Blocking CD44 interactions locally inhibited endometriotic lesion growth. Immunofluorescence results further confirmed that CD44 blocking inhibited pDC infiltration and reduced the frequency of CD44+ pDCs in endometriotic tissues. BBP also disrupted the estrus cycle in these mice. This study suggests that chronic exposure to low-dose BBP may promote survival of endometriotic tissue through CD44-expressing pDCs.

The Physiology of Reproduction – Quo vadis?

The reproductive system in males and females reflects a highly dynamic underlying physiology. Yet our current understanding of this system is still largely based upon relatively simplistic snapshots of individual component cells and tissues. Gamete production as well as gonadal hormone synthesis and its influence are the manifestations of dynamic and redundant informational networks and processes, whose qualitative and quantitative dimensions, especially through development from embryo through puberty and adulthood into ageing, are still largely uncharted. Whilst the recent huge advances in molecular science have helped to describe the components of the reproductive system in ever greater detail, how these interact and function in space and time dimensions is still largely obscure. Recent developments in microfluidics, stem cell biology, and the integration of single-cell transcriptomics with tissue dynamics are offering possible methodological solutions to this issue. Such knowledge is essential if we are to understand not only the normal healthy functioning of this system, but also how and why it is affected in disease or by external impacts such as those from environmental endocrine disruptors, or in ageing. Moreover, operating within a complex network of other physiological systems, its integrational capacity is much more than the generation of male and female gametes and their roles in fertility and infertility; rather, it represents the underpinning support for health and well-being across the lifespan, through pregnancy, puberty, and adulthood, into old age.

Bisphenol A Exposure Disrupts Organelle Distribution and Functions During Mouse Oocyte Maturation

Bisphenol A (BPA) is one of the ubiquitous environmental endocrine disruptors (EEDs). Previous studies have shown that the reproduction toxicity of BPA could cause severe effects on the mammal oocytes and disturb the quality of mature oocytes. However, the toxic effects of BPA on the organelles of mouse oocytes have not been reported. In this study, to investigate whether BPA can be toxic to the organelles, we used different concentrations of BPA (50, 100, and 200 μM) to culture mouse oocytes in vitro. The results showed that 100 μM BPA exposure could significantly decrease the developmental capacity of oocytes. Then, we used the immunofluorescence staining, confocal microscopy, and western blotting to investigate the toxic effects of BPA on the organelles. The results revealed that mitochondrial dysfunction is manifested by abnormal distribution and decreased mitochondrial membrane potential. Moreover, the endoplasmic reticulum (ER) is abnormally distributed which is accompanied by ER stress showing increased expression of GRP78. For the Golgi apparatus, BPA-exposed dose not disorder the Golgi apparatus distribution but caused abnormal structure of Golgi apparatus, which is manifested by the decrease of GM130 protein expression. Moreover, we also found that BPA-exposed led to the damage of lysosome, which were shown by the increase of LAMP2 protein expression. Collectively, our findings demonstrated that the exposure of BPA could damage the normal function of the organelles, which may explain the reduced maturation quality of oocytes.

In situ formation of environmental endocrine disruptors from phytosterol degradation: a temporal model for agricultural soils

Phytosterol (i.e. β-sitosterol) from crop residue decay and soil fertilization can in situ form steroid hormones, surpassing added sex steroids excreted by livestock and humans.

Can probiotics win the battle against environmental endocrine disruptors?

Compounds that have negative effects on the endocrine system are called endocrine disrupting compounds (EDCs). There are several different types of compounds, with several different usage areas in the environment, which can be classified as EDCs. These chemicals have a wide range of negative health effects in organisms, depending on their target hormone system. EDCs are among the most popular topics of scientific research, as they are widely used and organisms are frequently exposed to these chemicals. There are various exposure routes for EDCs, such as oral, inhalation and dermal exposure. Parabens, phenolic compounds, phthalates, and pesticides are the most common EDCs. Nowadays, intestinal microorganism distribution, probiotics, and food supplements that regulate these microorganisms and their protective effects against various harmful chemicals attract attention. For this reason, many studies have been carried out in this field and certain diet schemes have been created according to the results of these studies. In fact, probiotics are preferred in order to reduce and eliminate the negative effects of harmful chemicals and to ensure that the organism reacts strongly in these conditions. In this review, we will focus on EDCs, their health effects and positive effects of probiotics on EDCs exposure conditions.