scholarly journals Effects of endocrine disruptors on fetal testis development, male puberty, and transition age

Endocrine ◽  
2020 ◽  
Author(s):  
Francesco Cargnelutti ◽  
Andrea Di Nisio ◽  
Francesco Pallotti ◽  
Iva Sabovic ◽  
Matteo Spaziani ◽  
...  
Keyword(s):  
Endocrine Disruptors ◽  
Reproductive System ◽  
Current Evidence ◽  
Transition Age ◽  
Testis Development ◽  
Fetal Testis ◽  
Male Puberty ◽  
The Impact ◽  
Harmful Effects

Abstract Purpose Endocrine disruptors (EDs) are exogenous substances able to impair endocrine system; consequently, they may cause numerous adverse effects. Over the last years, particular focus has been given to their harmful effects on reproductive system, but very little is known, especially in males. The aim of this review is to discuss the detrimental effects of EDs exposure on fetal testis development, male puberty, and transition age. Methods A search for the existing literature focusing on the impact of EDs on fetal testis development, male puberty, andrological parameters (anogenital distance, penile length, and testicular volume), and testicular cancer with particular regard to pubertal age provided the most current information available for this review. Human evidence-based reports were given priority over animal and in vitro experimental results. Given the paucity of available articles on this subject, all resources were given careful consideration. Results Information about the consequences associated with EDs exposure in the current literature is limited and often conflicting, due to the scarcity of human studies and their heterogeneity. Conclusions We conclude that current evidence does not clarify the impact of EDs on human male reproductive health, although severe harmful effects had been reported in animals. Despite controversial results, overall conclusion points toward a positive association between exposure to EDs and reproductive system damage. Further long-term studies performed on wide number of subjects are necessary in order to identify damaging compounds and remove them from the environment.

scholarly journals Correction to: Effects of endocrine disruptors on fetal testis development, male puberty, and transition age

Endocrine ◽  
2021 ◽  
Author(s):  
Francesco Cargnelutti ◽  
Andrea Di Nisio ◽  
Francesco Pallotti ◽  
Iva Sabovic ◽  
Matteo Spaziani ◽  
...  
Keyword(s):  
Endocrine Disruptors ◽  
Transition Age ◽  
Testis Development ◽  
Fetal Testis ◽  
Male Puberty

scholarly journals Pesticides as endocrine distruptors of the reproductive system (literature review and own research)

2021 ◽  
pp. 49-62
Author(s):  
Ninel Shepelska ◽  
Mykola Prodanchuk ◽  
Yana Kolianchuk
Keyword(s):  
Reproductive Health ◽  
Endocrine Disruptors ◽  
Reproductive System ◽  
Reproductive Toxicity ◽  
Endocrine System ◽  
Reproductive Function ◽  
Dose Dependence ◽  
Animal Cells ◽  
Wide Range ◽  
The Impact

Currently, one of the main threats to human health is undoubtedly endocrine disruptors (ED), since they directly disrupt the processes of homeostasis maintenance, controlled by the endocrine system, the purpose of which is to maintain normal functions and development in a constantly changing environment. Pesticides can disrupt the physiological functioning of many endocrine axes, including the endocrine mechanisms that ensure reproductive health. It should be noted that research aimed at preventing chemically induced reproductive disorders in the human population is one of the central areas of preventive medicine, both in terms of their importance and the complexity of the tasks being solved. Analysis and generalization of the results of our own long-term studies have shown that the selective, and, therefore, the most dangerous toxicity of pesticides for the reproductive system is determined by endocrine-mediated mechanisms of etiopathogenesis. The low level of doses inducing pathological changes in reproductive function in our studies fully confirms one of the universal signs inherent in endocrine-distruptive compounds. The above examples demonstrate a wide range of possible endocrine-mediated mechanisms of reproductive toxicity of pesticides - endocrine disruptors. However, it is very important to note that low doses may be more effective in changing some endpoints compared to high (toxic) doses. Currently, several mechanisms have been identified and studied that demonstrate how hormones and ED induce non-monotonic reactions in animal cells, tissues and organs. The reproductive system, the functioning of which is ensured by a fine balancing of the action of androgens and estrogens, is one of the systems that presents a unique opportunity for modeling a non-monotonic dose dependence. All of the above indicates the extreme danger of the impact of hormonally active agents on the reproductive health of a person and his offspring. At the same time, the threat of endocrine-mediated disorders for subsequent generations can also be realized through the induction of mechanisms of development of epigenetic transgenerational effects. Taking into account the results of studies of the mechanisms of the ED destructive action, as well as their ability to induce non-monotonic dose dependence at an extremely low dose level, it should be admitted that, apparently, there is a need to revise the paradigm of methodological approaches to the regulation of pesticides with endocrine-disruptive properties. Key words: pesticides, endocrine disruptors, reproductive system

scholarly journals The Impact of Uremic Toxins on Cerebrovascular and Cognitive Disorders

Toxins ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 303 ◽  
Author(s):  
Maryam Assem ◽  
Mathilde Lando ◽  
Maria Grissi ◽  
Saïd Kamel ◽  
Ziad Massy ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Cognitive Disorders ◽  
Neurological Complications ◽  
Cerebrovascular Diseases ◽  
Uremic Toxins ◽  
Current Evidence ◽  
Cognitive Disorders And Dementia ◽  
The Impact

Individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia. Stroke is also highly prevalent in this population and is associated with a higher risk of neurological deterioration, in-hospital mortality, and poor functional outcomes. Evidence from in vitro studies and in vivo animal experiments suggests that accumulation of uremic toxins may contribute to the pathogenesis of stroke and amplify vascular damage, leading to cognitive disorders and dementia. This review summarizes current evidence on the mechanisms by which uremic toxins may favour the occurrence of cerebrovascular diseases and neurological complications in CKD.

168. TGFβ 2-BETAGLYCAN REGULATE FOETAL TESTIS DEVELOPMENT IN VITRO

2010 ◽  
Vol 22 (9) ◽  
pp. 86
Author(s):  
M. A. Sarraj ◽  
A. Umbers ◽  
J. K. Findlay ◽  
K. L. Stenvers
Keyword(s):  
Target Cells ◽  
Wildtype Mouse ◽  
Culture Methods ◽  
Agar Block ◽  
Testis Development ◽  
Fetal Testis ◽  
Methods Development ◽  
Development In Vitro ◽  
Tgfβ Superfamily

Betaglycan is a co-receptor for the TGFβ superfamily, known to modulate TGFβ binding in target cells. We have previously found that betaglycan null murine testes at 12.5-13.5 dpc display poorly delineated seminiferous cords and disrupted Leydig cell development (1). Both TGFβs and inhibins are expressed by the fetal testis and it is currently unclear which regulate its development. We tested the hypothesis that loss of betaglycan compromises the functions of TGFβ2 in the differentiating fetal testis as TGFβ2 is known to bind poorly to its type II receptor in the absence of betaglycan. We tested the effect of TGFβ2 on betaglycan wildtype and null foetal gonad/mesonephros complexes using hanging drop or agar block culture methods. From each embryo, one gonad acted as a control; the other was treated. Gonads were cultured in the presence or absence of TGFβ2 (2.5-5 ng/mL) for 48 hours (n =3 pairs). In both culture methods, development in the absence of exogenous growth factor recapitulated normal cord development in wildtype testis and the disrupted cord phenotype in null testes. TGFβ2-treated cultures, 13.5 dpc wildtype mouse testes displayed a 14-35% reduction in total area compared to untreated cultures. Null testes exhibited significantly smaller reductions in gonadal area (2-13%; P < 0.01), indicating that betaglycan null testes exhibit reduced sensitivity to TGFβ2-mediated growth inhibition. However, preliminary observations suggest that TGFβ2 treatment partly rescued cord formation in two of three betaglycan knockout testes in vitro, with testis morphology confirmed by laminin and AMH immunostaining. These data support the notion that TGFβ2 acts via betaglycan to regulate cord development during foetal testis development. Supported by the New Investigator NHMRC (AUS) grant #550915 to MS, JKF Fellowship (#441101, #550915, #338516;#241000) and Victorian Government infrastructure funds. (1) Sarraj et al., 2010. Biol Reprod; 82(1): 153–62.

scholarly journals Investigating the importance of individual mitochondrial genotype in susceptibility to drug-induced toxicity

2020 ◽  
Vol 48 (3) ◽  
pp. 787-797
Author(s):  
Sophie L. Penman ◽  
Alice S. Carter ◽  
Amy E. Chadwick
Keyword(s):  
Clinical Data ◽  
Research Effort ◽  
Personalised Medicine ◽  
Current Evidence ◽  
Mitochondrial Genetics ◽  
Drug Induced ◽  
Mitochondrial Haplogroup ◽  
Mtdna Variation ◽  
The Impact

The mitochondrion is an essential organelle responsible for generating cellular energy. Additionally, mitochondria are a source of inter-individual variation as they contain their own genome. Evidence has revealed that mitochondrial DNA (mtDNA) variation can confer differences in mitochondrial function and importantly, these differences may be a factor underlying the idiosyncrasies associated with unpredictable drug-induced toxicities. Thus far, preclinical and clinical data are limited but have revealed evidence in support of an association between mitochondrial haplogroup and susceptibility to specific adverse drug reactions. In particular, clinical studies have reported associations between mitochondrial haplogroup and antiretroviral therapy, chemotherapy and antibiotic-induced toxicity, although study limitations and conflicting findings mean that the importance of mtDNA variation to toxicity remains unclear. Several studies have used transmitochondrial cybrid cells as personalised models with which to study the impact of mitochondrial genetic variation. Cybrids allow the effects of mtDNA to be assessed against a stable nuclear background and thus the in vitro elucidation of the fundamental mechanistic basis of such differences. Overall, the current evidence supports the tenet that mitochondrial genetics represent an exciting area within the field of personalised medicine and drug toxicity. However, further research effort is required to confirm its importance. In particular, efforts should focus upon translational research to connect preclinical and clinical data that can inform whether mitochondrial genetics can be useful to identify at risk individuals or inform risk assessment during drug development.

scholarly journals Metabolic Aspects of Anthracycline Cardiotoxicity

2021 ◽  
Vol 22 (2) ◽  
Author(s):  
Michele Russo ◽  
Angela Della Sala ◽  
Carlo Gabriele Tocchetti ◽  
Paolo Ettore Porporato ◽  
Alessandra Ghigo
Keyword(s):  
Heart Failure ◽  
Anticancer Agents ◽  
Energy Demand ◽  
Cardiac Metabolism ◽  
Current Evidence ◽  
Anthracycline Cardiotoxicity ◽  
Cardiac Side Effects ◽  
The Impact

Opinion statementHeart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. At the molecular level, cardiac side effects of DOXO have been associated to mitochondrial dysfunction, DNA damage, impairment of iron metabolism, apoptosis, and autophagy dysregulation. On these bases, the antioxidant and iron chelator molecule, dexrazoxane, currently represents the unique FDA-approved cardioprotectant for patients treated with anthracyclines.A less explored area of research concerns the impact of DOXO on cardiac metabolism. Recent metabolomic studies highlight the possibility that cardiac metabolic alterations may critically contribute to the development of DOXO cardiotoxicity. Among these, the impairment of oxidative phosphorylation and the persistent activation of glycolysis, which are commonly observed in response to DOXO treatment, may undermine the ability of cardiomyocytes to meet the energy demand, eventually leading to energetic failure. Moreover, increasing evidence links DOXO cardiotoxicity to imbalanced insulin signaling and to cardiac insulin resistance. Although anti-diabetic drugs, such as empagliflozin and metformin, have shown interesting cardioprotective effects in vitro and in vivo in different models of heart failure, their mechanism of action is unclear, and their use for the treatment of DOXO cardiotoxicity is still unexplored.This review article aims at summarizing current evidence of the metabolic derangements induced by DOXO and at providing speculations on how key players of cardiac metabolism could be pharmacologically targeted to prevent or cure DOXO cardiomyopathy.

Acupuncture and in vitro fertilisation research: Current and future directions

2018 ◽  
Vol 36 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Lee E Hullender Rubin ◽  
Belinda J Anderson ◽  
LaTasha B Craig
Keyword(s):  
Stress Reduction ◽  
Endometrial Thickness ◽  
Current Evidence ◽  
In Vitro Fertilisation ◽  
Future Directions ◽  
Acupuncture Intervention ◽  
Related Stress ◽  
The Impact ◽  
Improve Patient

Background Acupuncture is a common adjuvant treatment to support patients undergoing in vitro fertilisation (IVF). However, the impact of acupuncture and the different roles it can play in IVF remain unclear. Objective In this paper, we present an overview and critique of the current evidence on acupuncture's impact on IVF-related stress, describe harms, and propose future directions for investigation. Conclusion Two to three acupuncture sessions performed on or around the day of embryo transfer are insufficient interventions to improve IVF birth outcomes but provide significant IVF-related stress reduction. Research investigating acupuncture to support IVF is heterogeneous and confounded by the lack of an appropriate comparator. However, evidence suggests several acupuncture sessions improve endometrial thickness, reduce stress, and improve patient satisfaction. Observational studies suggest more sessions are associated with increases in clinical pregnancy and live birth rates. An optimised acupuncture intervention with a reasonable comparator is necessary for future studies, with evidence-based guidance on technique and number of sessions. Acupuncture should not be rejected as an adjuvant therapy for IVF, but more studies are needed to clarify acupuncture's role in supporting IVF cycles.

The impact of EPA and DHA on ceramide lipotoxicity in the metabolic syndrome

2020 ◽  
pp. 1-13
Author(s):  
Chelsey Walchuk ◽  
Yidi Wang ◽  
Miyoung Suh
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Animal Studies ◽  
Sphingolipid Metabolism ◽  
Current Evidence ◽  
The Metabolic Syndrome ◽  
Epa And Dha ◽  
The Impact

Abstract The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, insulin resistance (IR) and dyslipidaemia. Consumption of a high-fat diet (HFD) enriched in SFA leads to the accumulation of ceramide (Cer), the central molecule in sphingolipid metabolism. Elevations in plasma and tissue Cer are found in obese individuals, and there is evidence to suggest that Cer lipotoxicity contributes to the MetS. EPA and DHA have shown to improve MetS parameters including IR, inflammation and hypertriacylglycerolaemia; however, whether these improvements are related to Cer is currently unknown. This review examines the potential of EPA and DHA to improve Cer lipotoxicity and MetS parameters including IR, inflammation and dyslipidaemia in vitro and in vivo. Current evidence from cell culture and animal studies indicates that EPA and DHA attenuate palmitate- or HFD-induced Cer lipotoxicity and IR, whereas evidence in humans is greatly lacking. Overall, there is intriguing potential for EPA and DHA to improve Cer lipotoxicity and related MetS parameters, but more research is warranted.

scholarly journals The impact of endocrine disruptors on oocyte competence

Reproduction ◽  
2003 ◽  
pp. 313-325 ◽  
Author(s):  
P Pocar ◽  
TA Brevini ◽  
B Fischer ◽  
F Gandolfi
Keyword(s):  
Endocrine Disruptors ◽  
In Vitro Models ◽  
Environmental Chemicals ◽  
Farm Animals ◽  
Published Data ◽  
Environmental Matrices ◽  
Oocyte Competence ◽  
Natural Hormone ◽  
The Impact

To date, approximately 60 chemicals have been identified as endocrine disruptors: exogenous agents that interfere with various aspects of natural hormone physiology. The potential reproductive and health hazards of these environmental chemicals have recently generated concern among the scientific community, policy makers and general public. The present review presents and discusses the available evidence that environmental chemicals are causing ovarian toxicity in various species, with particular attention to farm animals. The impact of chronic exposure to endocrine disruptors via food and drinking water cannot be neglected when studying fertility problems in these species. This review focuses attention on the superfamily of organochlorine chemicals, persistent organic pollutants (POPs), because of their persistence in the environment, ability to concentrate up the food chain, continued detection in environmental matrices and ability to be stored in the adipose tissue of animals and humans. Published data clearly indicate that POPs disrupt mammalian oocyte maturation and follicle physiology in every species studied so far, including farm animals. However, as most of the data available still derive from experiments performed on laboratory species or in vitro models, great care should be taken when extrapolations to other species or environmental situations are attempted.

scholarly journals An updated overview of e-cigarette impact on human health

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Patrice Marques ◽  
Laura Piqueras ◽  
Maria-Jesus Sanz
Keyword(s):  
Human Health ◽  
Tobacco Consumption ◽  
Heating Process ◽  
Long Term Effects ◽  
Safe Alternative ◽  
The Impact ◽  
Harmful Effects

AbstractThe electronic cigarette (e-cigarette), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes, tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users. Nevertheless, the safety of e-cigarette consumption and its potential as a smoking cessation method remain controversial due to limited evidence. Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health. Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described. Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease 2019 (COVID-19).

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