scholarly journals Testicular dysgenesis syndrome and phthalate exposure: A review of literature

2021 ◽  
Vol 71 (6) ◽  
pp. 508-543
Author(s):  
Pınar Erkekoglu ◽  
Aylin Özyurt ◽  
Anıl Yirün ◽  
Deniz Çakır
Keyword(s):  
Endocrine Disruptors ◽  
Semen Quality ◽  
Pathological Condition ◽  
Endocrine System ◽  
Seminiferous Tubules ◽  
Testicular Dysgenesis Syndrome ◽  
Testicular Cells ◽  
Phthalate Exposure ◽  
Food Packages ◽  
Testicular Dysgenesis

Endocrine disruptors are chemicals that interfere with the body's endocrine system and cause adverse effects in biological systems. Phthalates are a group of man-made chemicals which are mainly used as plasticizers and classified as endocrine disruptors. They are also used in cosmetic and personal care products as color or smell fixators. Moreover, phthalates are present in inks, adhesives, sealants, automobile parts, tools, toys, carpets, medical tubing and blood storage bags, and food packages. Pathological condition known as "testicular dysgenesis syndrome" (TDS) or "phthalate syndrome" is usually linked to phthalate exposure and is coined to describe the rise in alterations in reproductive health in men, such as reduced semen quality (decrease in sperm counts, sperm motility and increase in abnormal sperms), hypospadias, cryptorchidism, reduced anogenital distance and early-life testicular cancer. Phthalates are suggested to cause direct effect on gonadal and non-gonadal tissues, impair the differentiation and morphogenesis of seminiferous tubules and accessory sex organs and testicular cells (both Sertoli and Leydig cells), alter estradiol and/or testosterone levels, decrease insulin-like 3 (INSL3) peptide production, impair spermatogenesis and lead to epigenetic alterations, all of which may lead to TDS. This review will mainly focus on phthalates as causes of TDS and their mechanisms of action.

Restraint stress of male mice triggers apoptosis in spermatozoa and spermatogenic cells via activating the TNF-α system

Zygote ◽  
2020 ◽  
Vol 28 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Jie Zhang ◽  
De-Ling Kong ◽  
Bin Xiao ◽  
Hong-Jie Yuan ◽  
Qiao-Qiao Kong ◽  
...  
Keyword(s):  
Psychological Stress ◽  
Restraint Stress ◽  
Semen Quality ◽  
Sperm Quality ◽  
Fertilization Rate ◽  
Seminiferous Tubules ◽  
Spermatogenic Cells ◽  
Male Mice ◽  
Testicular Cells ◽  
Tnf Α

SummaryStudies have indicated that psychological stress impairs human fertility and that various stressors can induce apoptosis of testicular cells. However, the mechanisms by which psychological stress on males reduces semen quality and stressors induce apoptosis in testicular cells are largely unclear. Using a psychological (restraint) stress mouse model, we tested whether male psychological stress triggers apoptosis of spermatozoa and spermatogenic cells through activating tumour necrosis factor (TNF)-α signalling. Wild-type or TNF-α−/− male mice were restrained for 48 h before examination for apoptosis and expression of TNF-α and TNF receptor 1 (TNFR1) in spermatozoa, epididymis, seminiferous tubules and spermatogenic cells. The results showed that male restraint significantly decreased fertilization rate and mitochondrial membrane potential, while increasing levels of malondialdehyde, active caspase-3, TNF-α and TNFR1 in spermatozoa. Male restraint also increased apoptosis and expression of TNF-α and TNFR1 in caudae epididymides, seminiferous tubules and spermatogenic cells. Sperm quality was also significantly impaired when spermatozoa were recovered 35 days after male restraint. The restraint-induced damage to spermatozoa, epididymis and seminiferous tubules was significantly ameliorated in TNF-α−/− mice. Furthermore, incubation with soluble TNF-α significantly reduced sperm motility and fertilizing potential. Taken together, the results demonstrated that male psychological stress induces apoptosis in spermatozoa and spermatogenic cells through activating the TNF-α system and that the stress-induced apoptosis in spermatogenic cells can be translated into impaired quality in future spermatozoa.

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 Effects of phthalic acid esters on fetal health

2014 ◽  
Vol 67 (5-6) ◽  
pp. 172-175 ◽  
Author(s):  
Ivana Bajkin ◽  
Artur Bjelica ◽  
Tijana Icin ◽  
Vesna Dobric ◽  
Branka Kovacev-Zavisic ◽  
...  
Keyword(s):  
Endocrine System ◽  
Vulnerable Groups ◽  
Negative Consequences ◽  
Negative Effects ◽  
Duration Of Action ◽  
Testicular Dysgenesis Syndrome ◽  
Stage Of Development ◽  
Testicular Dysgenesis ◽  
High Concentrations ◽  
The Individual

Introduction. Phthalates are synthetic industrial compounds capable of disrupting endocrine system. Effects of phthalates depend on dosage, duration of action and stage of development of the individual, thus making the fetus, newborn, and children at puberty the most vulnerable groups. Metabolism of Phthalates: Metabolism of these compounds consists of at least two steps: hydrolysis and conjugation. They are mainly excreted in urine, with a low percent being excreted through feces. Exposure to Phthalates. Exposure to the effects of phthalates begins at the intrauterine stage since the phthalates pass through the placental barrier. Phthalates may be found in plastic products, toys, medical equipment, industrial materials, food, and clothes. Determination of Phthalate Levels in Humans. Urine is the best sample for evaluating phthalate levels in humans because of rapid phthalate metabolism and high concentrations of metabolites in the urine. Fetal Testicular Dysgenesis Syndrome: Fetal testicular dysgenesis syndrome involves disorders of male genital tract such as shortened anogenital distance, hypospadia, cryptorchidism, malformations of seminal vesicles, prostate, epididymis and it results from the harmful effects of phthalates. Other Effects of Phthalates on Health. Negative effects of phthalates on female health are mostly reflected in anovulation, premature puberty, changes in duration of pregnancy. There is a possible effect on neurocognitive development, occurrence of allergies, asthma, testicular carcinoma, hepatic and renal damages, insulin resistance and obesity, thyroid dysfunction. Conclusion. Further studies are needed to establish the safe phthalate concentration in certain products and to determine more negative consequences of exposure to phthalate.

scholarly journals Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility

2016 ◽  
Vol 96 (1) ◽  
pp. 55-97 ◽  
Author(s):  
Niels E. Skakkebaek ◽  
Ewa Rajpert-De Meyts ◽  
Germaine M. Buck Louis ◽  
Jorma Toppari ◽  
Anna-Maria Andersson ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Semen Quality ◽  
Disorders Of Sex Development ◽  
Endocrine System ◽  
Environmental Exposures ◽  
The United States ◽  
Testicular Dysgenesis Syndrome ◽  
Fertility Trends ◽  
Sex Development ◽  
Reproductive Techniques

It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

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 GENETIC ASPECTS OF TESTICULAR DYSGENESIS SYNDROME AND ASSOCIATED CONDITIONS

2018 ◽  
Vol 14 (3) ◽  
pp. 92-106
Author(s):  
M. V. Nemtsova ◽  
I. S. Dantsev ◽  
D. S. Mikhaylenko ◽  
O. V. Loran
Keyword(s):  
Germ Cell ◽  
Genetic Factors ◽  
Semen Quality ◽  
Germ Cell Tumors ◽  
Abnormal Development ◽  
Testicular Microlithiasis ◽  
Testicular Germ Cell ◽  
Testicular Dysgenesis Syndrome ◽  
Factors Associated ◽  
Testicular Dysgenesis

Today it is noted that the most cases of the hypospadias, cryptorchidism, testicular microlithiasis, as well as problems of semen quality and testicular germ cell tumours can be a clinical manifestation of testicular dysgenesis syndrome caused by abnormal development of reproductive organs. In the last decade, technological progress in the molecular genetics has made possible to carry out a directed search for genetic factors associated with reproductive disorders in men. In the review we attempted to analyze available literature data on the testicular dysgenesis syndrome and its constituent condition and also to consider the risk factors associated with its development. We give particular attention to the consideration of genetic factors that determine the manifestation of testicular microlithiasis, cryptorchidism and testicular germ cell tumors, both individual clinical conditions and in the syndrome of testicular dysgenesis. Knowledge of the genetic aspects of reproductive damage will allow us to characterize the complex interconnection of the human genome with the clinical phenotype, clarify the role of unfavorable factors of the environment and the lifestyle of the individual, and suggest new approaches to treatment.

The Male Reproductive System and Endocrine Disruptors

2021 ◽  
Vol 21 ◽  
Author(s):  
Schiesaro Mauro Giovanni ◽  
Amato Anna Maria Letizia ◽  
Maneschi Chiara ◽  
Sciabica Vincenzo ◽  
Pigatto Erika ◽  
...  
Keyword(s):  
Endocrine Disruptors ◽  
Reproductive System ◽  
Semen Quality ◽  
Reproductive Function ◽  
In Vitro Models ◽  
Male Reproductive System ◽  
Future Research ◽  
Testicular Dysgenesis Syndrome ◽  
Hormonal Milieu

: The male reproductive system is exposed to a great number of chemical substances which can interfere with the normal hormonal milieu and reproductive function; these are called endocrine disruptors (EDs). Despite a growing number of studies evaluating the negative effects of EDs, their production is continuously growing although some of which have been prohibited. The prevalence of poor semen quality, hypospadias, cryptorchidism, and testicular cancer have increased in the last decades, and recently, it has been postulated that these could all be part of a unique syndrome called testicular dysgenesis syndrome. This syndrome could be related to exposure to a number of EDs which cause imbalances in the hormonal milieu and oestrogenic over-exposure during the foetal stage. The same EDs can also impair spermatogenesis in offspring and have epigenetic effects. Although studies on animal and in vitro models have raised concerns, data are conflicting. However, these studies must be considered as the basis for future research to promote male reproductive health.

scholarly journals Insights into the Mechanism of Bovine Spermiogenesis Based on Comparative Transcriptomic Studies

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 80
Author(s):  
Xin Li ◽  
Chenying Duan ◽  
Ruyi Li ◽  
Dong Wang
Keyword(s):  
Gene Expression ◽  
Semen Quality ◽  
Regulation Of Gene Expression ◽  
Physiological Mechanism ◽  
Interaction Network ◽  
Seminiferous Tubules ◽  
Differential Analysis ◽  
Epididymal Sperm ◽  
Bioinformatics Analyses ◽  
Acrosome Formation

To reduce subfertility caused by low semen quality and provide theoretical guidance for the eradication of human male infertility, we sequenced the bovine transcriptomes of round, elongated spermatids and epididymal sperms. The differential analysis was carried out with the reference of the mouse transcriptome, and the homology trends of gene expression to the mouse were also analysed. First, to explore the physiological mechanism of spermiogenesis that profoundly affects semen quality, homological trends of differential genes were compared during spermiogenesis in dairy cattle and mice. Next, Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment, protein–protein interaction network (PPI network), and bioinformatics analyses were performed to uncover the regulation network of acrosome formation during the transition from round to elongated spermatids. In addition, processes that regulate gene expression during spermiogenesis from elongated spermatid to epididymal sperm, such as ubiquitination, acetylation, deacetylation, and glycosylation, and the functional ART3 gene may play important roles during spermiogenesis. Therefore, its localisation in the seminiferous tubules and epididymal sperm were investigated using immunofluorescent analysis, and its structure and function were also predicted. Our findings provide a deeper understanding of the process of spermiogenesis, which involves acrosome formation, histone replacement, and the fine regulation of gene expression.

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

scholarly journals Germ cell-induced immune suppression in mice. Effect of inoculation of syngeneic spermatozoa on cell-mediated immune responses.

1982 ◽  
Vol 155 (6) ◽  
pp. 1719-1729 ◽  
Author(s):  
U Hurtenbach ◽  
G M Shearer
Keyword(s):  
Germ Cells ◽  
Immune Suppression ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Seminiferous Tubules ◽  
Immune Functions ◽  
Cytotoxic Lymphocyte ◽  
Testicular Cells ◽  
Killer Cell Activity

Spleen cells from mice injected intravenously with syngeneic male germ cells exhibited reduced immune functions as determined by natural killer cell activity, mixed lymphocyte reactivity and cytotoxic lymphocyte (CTL) function. The decrease in CTL responses to trinitrophenyl-modified self (TNP-self) was detected as early as 4 d after sperm injection and was observed to H-2 alloantigens 3 wk after injection. Radiosensitive suppressor T cells were found to suppress the CTL response to TNP-self. Suppression lasted for a period of at least 7 wk after a single inoculation of the germ cells. Some variability in immune suppression capability was observed using different preparations of germ cells which are not yet completely understood. Sperm were more effective in inducing suppression than testicular cells derived from the seminiferous tubules. Furthermore, sperm from older animals were more effective than those from younger mice. These findings are discussed with respect to possible regulatory influences of germ cells on the immune system when the blood-testes barrier is broken.

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