scholarly journals Phthalate-induced pathology in the foetal testis involves more than decreased testosterone production

Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 435-442 ◽  
Author(s):  
D N Rao Veeramachaneni ◽  
Gary R Klinefelter
Keyword(s):  
Reproductive Tract ◽  
Comprehensive Evaluation ◽  
Male Rats ◽  
Testicular Dysgenesis Syndrome ◽  
Pathway Network ◽  
New Findings ◽  
Testicular Dysgenesis ◽  
And Migration ◽  
And Function ◽  
Rats And Mice

Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have been noted; e.g., following foetal exposure, abnormal clustering of Leydig cells or decreased production of testosterone that is manifested in rats does not occur in mice or humans. Nonetheless, other facets of testicular dysgenesis occur in both rats and mice as well as in some other species tested. We recently published a comprehensive evaluation of the foetal rat testis proteome, following in utero exposure to diethylhexyl phthalate (DEHP), which revealed changes in individual proteins that are known to be factors in cellular differentiation and migration or related to the capacity of the foetal Leydig cell to produce testosterone and fit a pathway network in which each is regulated directly or indirectly by oestradiol. Plasma oestradiol indeed was found to be elevated approximately twofold in 19-day-old DEHP-exposed foetal male rats. In this brief review, we discuss our new findings vis-à-vis ‘oestrogen hypothesis’ as a cause for testicular dysgenesis syndrome.

scholarly journals Phthalate Toxicity in Rats and Its Relation to Testicular Dysgenesis Syndrome in Humans

2021 ◽  
pp. 019262332110453
Author(s):  
Cynthia J. Willson
Keyword(s):  
Reproductive Tract ◽  
Normal Development ◽  
Environmental Chemicals ◽  
Testicular Development ◽  
Reproductive Disorders ◽  
Male Reproductive Tract ◽  
Testicular Dysgenesis Syndrome ◽  
Human Male ◽  
Testicular Dysgenesis ◽  
Common Etiology

This work describes the relevance of toxicology studies of environmental chemicals, with a focus on phthalates, for a hypothesis that certain human male reproductive disorders and diseases have a common etiology of disturbance of normal development in utero. The “Testicular Dysgenesis Syndrome” hypothesis in humans has parallels in male reproductive tract abnormalities and microscopic lesions reported for phthalate toxicity in rats. Additionally, this work describes the histological findings of abnormal testicular development (testicular dysgenesis) in rats as compared to those in humans, as well as potential findings in rats at different ages, from the embryo to the adult.

scholarly journals Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome

Reproduction ◽  
2004 ◽  
Vol 127 (3) ◽  
pp. 305-315 ◽  
Author(s):  
Jane S Fisher
Keyword(s):  
Reproductive Health ◽  
Reproductive Tract ◽  
Semen Quality ◽  
Phthalate Esters ◽  
Male Reproductive Tract ◽  
Testicular Dysgenesis Syndrome ◽  
Geographical Variations ◽  
Human Male ◽  
Testicular Dysgenesis ◽  
Male Reproductive Health

The amount of research into endocrine disruption has exploded over the past decade and a re-evaluation of the state of research in this area is timely. There are debates about whether human male reproductive health is really declining and whether endocrine disrupting chemicals play any role in the perceived decline. Most data currently conclude that there are wide geographical variations in semen quality and in the incidence of testicular cancer, cryptorchidism and hypospadias. This review aims to give a brief overview of the issues surrounding the perceived decline in human male reproductive health and the importance of the hormonal environment for the development of the testis and reproductive tract. The consequences for the male reproductive tract of abnormal androgen levels or action are discussed with reference to environmental anti-androgenic compounds. The in vivo data on several anti-androgenic compounds that have been administered to pregnant rodents during the period of male reproductive tract development are assessed with attention to the effects on the male offspring. Finally, the data on in utero phthalate administration are discussed in detail to illustrate the similarities between the effects of some phthalate esters and the human male reproductive tract disorders which comprise testicular dysgenesis syndrome (TDS).

scholarly journals Testicular dysgenesis syndrome and the estrogen hypothesis: a quantitative meta-analysis

2008 ◽  
Vol 13 (5) ◽  
pp. 1601-1618 ◽  
Author(s):  
Olwenn Martin ◽  
Tassos Shialis ◽  
John Lester ◽  
Mark Scrimshaw ◽  
Alan Boobis ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Prenatal Exposure ◽  
Reproductive Tract ◽  
Meta Analysis ◽  
Gonadal Development ◽  
Fetal Life ◽  
End Points ◽  
Testicular Dysgenesis Syndrome ◽  
Summary Estimate ◽  
Testicular Dysgenesis

Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The only quantitative summary estimate of the link between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago; other reviews of the link between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-α-mediated mode of action was specifically explored. Eight studies were included, investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population.

scholarly journals Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol

Reproduction ◽  
2012 ◽  
Vol 144 (6) ◽  
pp. 747-761 ◽  
Author(s):  
Gary R Klinefelter ◽  
John W Laskey ◽  
Witold M Winnik ◽  
Juan D Suarez ◽  
Naomi L Roberts ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Semen Quality ◽  
Testicular Dysgenesis Syndrome ◽  
Pathway Network ◽  
Diethylhexyl Phthalate ◽  
Fetal Testis ◽  
Testosterone Production ◽  
Testicular Dysgenesis ◽  
Significant Research ◽  
Dehp Exposure

Significant research has been focused on phthalate-induced alterations in male reproductive development. Studies on rodents have prompted the notion that a syndrome exists in the human male which includes phenotypic alterations such as hypospadias, cryptorchidism, poor semen quality, and even testicular cancer. Each phenotype in this ‘testicular dysgenesis syndrome’ is predicated on reduction in testosterone production by the fetal Leydig cell. We sought to examine the relationship between dysgenesis and steroidogenic capacity in the fetal rat testis more stringently by incorporating lower exposures than those typically used, conducting a comprehensive, non-targeted quantitative evaluation of the fetal testis proteome, and relating alterations in individual proteins to the capacity of the fetal Leydig cell to produce testosterone, and histopathology of the fetal testis. Pregnant dams were dosed orally from gestation day (GD) 13–19 with 0, 10, or 100 mg diethylhexyl phthalate (DEHP)/kg body weight per day. Each endpoint was represented by 16 l. Clustering of Leydig cells occurred before any significant decrease in the capacity of the GD19 Leydig cell to produce testosterone. At 100 mg DEHP/kg, testosterone production was reduced significantly, Leydig cell clusters became quite large, and additional dysgenetic changes were observed in the fetal testis. Of 23 proteins whose expression was altered significantly at both DEHP exposure levels, seven were found to be correlated with and predictive of the quantified endpoints. None of these proteins have been previously implicated with DEHP exposure. Notably, pathway analysis revealed that these seven proteins fit a pathway network in which each is regulated directly or indirectly by estradiol.

scholarly journals Climate Mobility and Development Cooperation

2021 ◽  
Author(s):  
Robert Stojanov ◽  
Sarah Rosengaertner ◽  
Alex de Sherbinin ◽  
Raphael Nawrotzki
Keyword(s):  
Climate Adaptation ◽  
Human Mobility ◽  
Climate Impacts ◽  
Development Cooperation ◽  
Climate Variability And Change ◽  
Policy Frameworks ◽  
And Migration ◽  
And Function ◽  
Role And Function

AbstractDevelopment cooperation actors have been addressing climate change as a cross-cutting issue and investing in climate adaptation projects since the early 2000s. More recently, as concern has risen about the potential impacts of climate variability and change on human mobility, development cooperation actors have begun to design projects that intentionally address the drivers of migration, including climate impacts on livelihoods. However, to date, we know little about the development cooperation’s role and function in responding to climate related mobility and migration. As such, the main aim of this paper is to outline the policy frameworks and approaches shaping development cooperation actors’ engagement and to identify areas for further exploration and investment. First, we frame the concept of climate mobility and migration and discuss some applicable policy frameworks that govern the issue from various perspectives; secondly, we review the toolbox of approaches that development cooperation actors bring to climate mobility; and third, we discuss the implications of the current Covid-19 pandemic and identify avenues for the way forward. We conclude that ensuring safe and orderly mobility and the decent reception and long-term inclusion of migrants and displaced persons under conditions of more severe climate hazards, and in the context of rising nationalism and xenophobia, poses significant challenges. Integrated approaches across multiple policy sectors and levels of governance are needed. In addition to resources, development cooperation actors can bring data to help empower the most affected communities and regions and leverage their convening power to foster more coordinated approaches within and across countries.

scholarly journals From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

2021 ◽  
Vol 2 (2) ◽  
pp. 311-338
Author(s):  
Giulia Della Rosa ◽  
Clarissa Ruggeri ◽  
Alessandra Aloisi
Keyword(s):  
State Of The Art ◽  
Cell Communication ◽  
Pathological Conditions ◽  
New Findings ◽  
Cell Type Specific ◽  
New Perspective ◽  
And Function ◽  
And Personalized Medicine ◽  
Innate Ability

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

Testicular dysgenesis syndrome: foetal origin of adult reproductive problems

2009 ◽  
Vol 71 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Christine Wohlfahrt-Veje ◽  
Katharina M. Main ◽  
Niels Erik Skakkebaek
Keyword(s):  
Testicular Dysgenesis Syndrome ◽  
Testicular Dysgenesis
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