scholarly journals Signaling Proteins That Regulate Spermatogenesis Are the Emerging Target of Toxicant-Induced Male Reproductive Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Gao ◽  
Xiaolong Wu ◽  
Lingling Wang ◽  
Tiao Bu ◽  
Adolfo Perrotta ◽  
...  
Keyword(s):  
Cadmium Chloride ◽  
Endocrine Disrupting Chemicals ◽  
Signaling Cascade ◽  
Signaling Proteins ◽  
Environmental Toxicants ◽  
Reproductive Dysfunction ◽  
Male Contraceptive ◽  
Physiological Conditions ◽  
Endocrine Disrupting ◽  
Induced Defects

There is emerging evidence that environmental toxicants, in particular endocrine disrupting chemicals (EDCs) such as cadmium and perfluorooctanesulfonate (PFOS), induce Sertoli cell and testis injury, thereby perturbing spermatogenesis in humans, rodents and also widelife. Recent studies have shown that cadmium (e.g., cadmium chloride, CdCl2) and PFOS exert their disruptive effects through putative signaling proteins and signaling cascade similar to other pharmaceuticals, such as the non-hormonal male contraceptive drug adjudin. More important, these signaling proteins were also shown to be involved in modulating testis function based on studies in rodents. Collectively, these findings suggest that toxicants are using similar mechanisms that used to support spermatogenesis under physiological conditions to perturb Sertoli and testis function. These observations are physiologically significant, since a manipulation on the expression of these signaling proteins can possibly be used to manage the toxicant-induced male reproductive dysfunction. In this review, we highlight some of these findings and critically evaluate the possibility of using this approach to manage toxicant-induced defects in spermatrogenesis based on recent studies in animal models.

scholarly journals Transcriptomics and Other Omics Approaches to Investigate Effects of Xenobiotics on the Placenta

2021 ◽  
Vol 9 ◽  
Author(s):  
Cheryl S. Rosenfeld
Keyword(s):  
Expression Patterns ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine System ◽  
Environmental Toxicants ◽  
Bisphenol S ◽  
Extrinsic Factors ◽  
Placental Function ◽  
Organ Systems ◽  
Endocrine Disrupting ◽  
Pharmaceutical Agents

The conceptus is most vulnerable to developmental perturbation during its early stages when the events that create functional organ systems are being launched. As the placenta is in direct contact with maternal tissues, it readily encounters any xenobiotics in her bloodstream. Besides serving as a conduit for solutes and waste, the placenta possesses a tightly regulated endocrine system that is, of itself, vulnerable to pharmaceutical agents, endocrine disrupting chemicals (EDCs), and other environmental toxicants. To determine whether extrinsic factors affect placental function, transcriptomics and other omics approaches have become more widely used. In casting a wide net with such approaches, they have provided mechanistic insights into placental physiological and pathological responses and how placental responses may impact the fetus, especially the developing brain through the placenta-brain axis. This review will discuss how such omics technologies have been utilized to understand effects of EDCs, including the widely prevalent plasticizers bisphenol A (BPA), bisphenol S (BPS), and phthalates, other environmental toxicants, pharmaceutical agents, maternal smoking, and air pollution on placental gene expression, DNA methylation, and metabolomic profiles. It is also increasingly becoming clear that miRNA (miR) are important epigenetic regulators of placental function. Thus, the evidence to date that xenobiotics affect placental miR expression patterns will also be explored. Such omics approaches with mouse and human placenta will assuredly provide key biomarkers that may be used as barometers of exposure and can be targeted by early mitigation approaches to prevent later diseases, in particular neurobehavioral disorders, originating due to placental dysfunction.

Foods, exposures, and lifestyle risk factors in pregnancy and breastfeeding

2015 ◽  
Author(s):  
Sir Peter Gluckman ◽  
Mark Hanson ◽  
Chong Yap Seng ◽  
Anne Bardsley
Keyword(s):  
Pregnant Women ◽  
Endocrine Disrupting Chemicals ◽  
Evidence Base ◽  
Predatory Fish ◽  
Environmental Toxicants ◽  
Lifestyle Risk Factors ◽  
Endocrine Disrupting ◽  
Polycyclic Aromatic ◽  
Lifestyle Risk ◽  
Foodborne Infections

Advice for pregnant women on food avoidance, dangerous exposures, and inappropriate behaviours abounds on the internet and through various information sources. This chapter reviews the evidence base for such advice and clarifies issues where common advice is not supported by credible data. Foods containing potential teratogens, mutagens, or toxicants that need consideration include liver (high vitamin A), some herbal teas, contaminated grains, predatory fish, caffeine-containing foods, and various sources of foodborne infections. Exposure to environmental toxicants such as lead, pesticides, herbicides, polycyclic aromatic hydrocarbons, bisphenol-A, and other endocrine-disrupting chemicals should be avoided, as should alcohol consumption and cigarette smoking. Restrictive diets and unusual dietary cravings (pica) need to be properly managed. Evidence for harm from personal care products is generally weak, but pregnant women may choose to avoid some unnecessary exposures.

scholarly journals Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 143
Author(s):  
Ishfaq Ahmad Sheikh ◽  
Mohd Amin Beg
Keyword(s):  
Androgen Receptor ◽  
Binding Energy ◽  
Human Exposure ◽  
Endocrine Disrupting Chemicals ◽  
Crop Protection ◽  
Binding Pocket ◽  
Global Public Health ◽  
Reproductive Dysfunction ◽  
Endocrine Disrupting ◽  
Native Ligand

Endocrine-disrupting chemicals (EDCs) are a serious global public health and environmental concern. Pyrethroids are insecticide chemicals that are extensively used for crop protection and household purposes but have been identified as EDCs. On account of their ubiquitous environmental presence, human exposure occurs via food, dermal, or inhalation routes and is associated with health problems, including reproductive dysfunction. Permethrin is the most commonly used pyrethroid, and with two chiral centers in its structure, it has four stereoisomeric forms (two enantiomer pairs), i.e., permethrin (1R,3R)-cis, permethrin (1R,3S)-trans, permethrin (1S,3S)-cis, and permethrin (1S,3R)-trans. The current study was performed for predicting the potential endocrine-disrupting activity of the aforementioned four stereoisomers of permethrin against the androgen receptor (AR). The structural binding characterization and binding energy estimations in the AR binding pocket were done using induced fit docking. The structural binding data indicated that all stereoisomers were placed stably in the AR binding pocket and that the estimated binding energy values were comparable to the AR native ligand, except for permethrin (1S,3S)-cis. Furthermore, the commonality in the amino acid interactions to that of the AR native ligand and the binding energy values suggested the potential AR-disrupting activity of all the stereoisomers; however, stereoselective differences were not observed. Taken together, the results suggest that human exposure to permethrin, either as a racemate mixture or in individual stereoisomer form, could potentially interfere with AR function, which may lead to male reproductive dysfunction.

scholarly journals The Role of Endocrine Disruptors on Metabolic Dysfunction

2016 ◽  
Vol 10 (1) ◽  
pp. 108-121 ◽  
Author(s):  
Diogo Pestana ◽  
Diana Teixeira ◽  
Carla Sá ◽  
Luísa Correia-Sá ◽  
Valentina F. Domingues ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Endocrine Disrupting Chemicals ◽  
Environmental Toxicants ◽  
Metabolic Dysfunction ◽  
Contributing Factors ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Endocrine Disrupting

Abdominal obesity appears to be an important component of the metabolic syndrome (MetS), in which along with insulin resistance, hypertension and dyslipidaemia represents an increased risk for developing cardiovascular diseases and type 2 diabetes (T2D). The aetiology of obesity and its comorbidities is multifactorial, but despite the evidence of traditional contributing factors, the role of environmental toxicants with endocrine disrupting activity has been recently highlighted. Indeed, even small concentrations of these endocrine disrupting chemicals (EDCs) have the ability to cause severe health damages. In this revision, we focused our attention on the mechanisms of action and impact of EDCs exposure as a contributor to the present epidemics of obesity and MetS.The "environmental obesogens" hypothesis associates environmental EDCs to the disruption of energy homeostasis, with recent studies demonstrating the ability of these compounds to modulate the adipocyte biology. On the other hand, the distinct distribution pattern observed between two metabolically distinct AT depots (visceral and subcutaneous) and subsequent repercussion in the aggravation of metabolic dysfunction in a context of obesity, provides accumulating evidence to hypothesise that EDCs might have an important “environmental dysmetabolism” effect.However, in addition to adulthood exposure, the perinatal effects are very important, since it may allow a change in the metabolic programming, promoting the further development of obesity and MetS. Therefore, additional research directed at understanding the nature and action of EDCs will illuminate the connection between health and the environment and the possible effects triggered by these compounds in respect to public health.

scholarly journals Mitochondrial Epigenetics and Environmental Health: Making a Case for Endocrine Disrupting Chemicals

2020 ◽  
Vol 178 (1) ◽  
pp. 16-25
Author(s):  
Zheng Zhou ◽  
Jaclyn M Goodrich ◽  
Rita S Strakovsky
Keyword(s):  
Mitochondrial Dysfunction ◽  
Nuclear Dna ◽  
Endocrine Disrupting Chemicals ◽  
Dna Methyltransferases ◽  
Sufficient Evidence ◽  
Future Research ◽  
Environmental Toxicants ◽  
Additional Layer ◽  
Endocrine Disrupting ◽  
Epigenetic Disruption

Abstract Recent studies implicate mitochondrial dysfunction in the development and progression of numerous chronic diseases, which may be partially due to modifications in mitochondrial DNA (mtDNA). There is also mounting evidence that epigenetic modifications to mtDNA may be an additional layer of regulation that controls mitochondrial biogenesis and function. Several environmental factors (eg, smoking, air pollution) have been associated with altered mtDNA methylation in a handful of mechanistic studies and in observational human studies. However, little is understood about other environmental contaminants that induce mtDNA epigenetic changes. Numerous environmental toxicants are classified as endocrine disrupting chemicals (EDCs). Beyond their actions on hormonal pathways, EDC exposure is associated with elevated oxidative stress, which may occur through or result in mitochondrial dysfunction. Although only a few studies have assessed the impacts of EDCs on mtDNA methylation, the current review provides reasons to consider mtDNA epigenetic disruption as a mechanism of action of EDCs and reviews potential limitations related to currently available evidence. First, there is sufficient evidence that EDCs (including bisphenols and phthalates) directly target mitochondrial function, and more direct evidence is needed to connect this to mtDNA methylation. Second, these and other EDCs are potent modulators of nuclear DNA epigenetics, including DNA methylation and histone modifications. Finally, EDCs have been shown to disrupt several modulators of mtDNA methylation, including DNA methyltransferases and the mitochondrial transcription factor A/nuclear respiratory factor 1 pathway. Taken together, these studies highlight the need for future research evaluating mtDNA epigenetic disruption by EDCs and to detail specific mechanisms responsible for such disruptions.

Polymorphism in CYP1A1, GSTMI,GSTT1 genes and organochlorine pesticides in the etiology of hypospadias

2011 ◽  
Vol 30 (10) ◽  
pp. 1464-1474 ◽  
Author(s):  
Chandra ShekharYadav ◽  
Minu Bajpai ◽  
Vivek Kumar ◽  
Rafat Sultana Ahmed ◽  
Piyush Gupta ◽  
...  
Keyword(s):  
Organochlorine Pesticides ◽  
Endocrine Disrupting Chemicals ◽  
Environmental Toxicants ◽  
Increased Risk ◽  
Endocrine Disrupting ◽  
Steroidal Hormones ◽  
Endogenous Estrogen ◽  
Glutathione S Transferases ◽  
Pcr Method ◽  
Metabolizing Enzyme

Exposure to endocrine-disrupting chemicals (EDCs) and maternal endogenous estrogen may cause hypospadias, common congenital anomaly. Several organochlorine pesticides (OCPs) have been reported to possess an endocrine-disrupting potential. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTM1 and GSTT1) of xenobiotic metabolizing enzyme family are involved in the metabolism of various environmental toxicants and steroidal hormones. Hence, the present study was designed to evaluate the role of CYP1A1, GSTM1, GSTT1 genes polymorphism, OCPs levels and risk of hypospadias. A total of 80 hypospadiac and 120 age-matched control boys were included. OCP levels in blood were determined using Gas Chromatograph equipped with electron capture detector (GC-ECD) and polymorphism in CYP1A1, GSTM1 and GSTT1 genes was evaluated by RFLP and multiplex PCR method. We observed significant high levels of β-hexachlorohexane (HCH), γ-HCH, and p, p′-dichlorodiphenyl-dichloroethylene ( p,p’-DDE) in the cases. CYP1A1 polymorphisms were not significantly different among cases and controls, whereas concomitant deletion of GSTM1 and GSTT1 genotypes was significantly higher in cases as compared to controls. However, after adjusting for low birth weight and maternal occupational exposure, the results did not remain significant but odds of risk was higher (OR = 1.72, p = 0.14) among cases. In conclusion, our study suggests irrespective of genetic predisposition, higher level of some OCPs may be associated with increased risk of hypospadias.

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