scholarly journals Genetic and epigenetic alterations induced by bisphenol A exposure during different periods of spermatogenesis: from spermatozoa to the progeny

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marta Lombó ◽  
Cristina Fernández-Díez ◽  
Silvia González-Rojo ◽  
María Paz Herráez

AbstractExposure to bisphenol A (BPA) has been related to male reproductive disorders. Since this endocrine disruptor also displays genotoxic and epigenotoxic effects, it likely alters the spermatogenesis, a process in which both hormones and chromatin remodeling play crucial roles. The hypothesis of this work is that BPA impairs early embryo development by modifying the spermatic genetic and epigenetic information. Zebrafish males were exposed to 100 and 2000 μg/L BPA during early spermatogenesis and during the whole process. Genotoxic and epigenotoxic effects on spermatozoa (comet assay and immunocytochemistry) as well as progeny development (mortality, DNA repairing activity, apoptosis and epigenetic profile) were evaluated. Exposure to 100 µg/L BPA during mitosis slightly increased sperm chromatin fragmentation, enhancing DNA repairing activity in embryos. The rest of treatments promoted high levels of sperm DNA damage, triggering apoptosis in early embryo and severely impairing survival. Regarding epigenetics, histone acetylation (H3K9Ac and H3K27Ac) was similarly enhanced in spermatozoa and embryos from males exposed to all the treatments. Therefore, BPA male exposure jeopardizes embryonic survival and development due to the transmission of a paternal damaged genome and of a hyper-acetylated histone profile, both alterations depending on the dose of the toxicant and the temporal window of exposure.

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 289
Author(s):  
Joana Santiago ◽  
Joana V. Silva ◽  
Manuel A. S. Santos ◽  
Margarida Fardilha

Bisphenol A (BPA), a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic–pituitary–gonadal axis and inducing oxidative stress in testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestradiol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, and sperm DNA damage. Recent studies explored potential approaches to treat or prevent BPA-induced testicular toxicity and male infertility. Since the effect of BPA on testicular cells and spermatozoa is associated with an increased production of reactive oxygen species, most of the pharmacological approaches are based on the use of natural or synthetic antioxidants. In this review, we briefly describe the effects of BPA on male reproductive health and discuss the use of antioxidants to prevent or revert the BPA-induced toxicity and infertility in men.


Reproduction ◽  
2009 ◽  
Vol 138 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Carmen López-Fernández ◽  
Matthew J G Gage ◽  
Francisca Arroyo ◽  
Altea Gosálbez ◽  
Ana M Larrán ◽  
...  

Spermatozoal haplotypic DNA is prone to damage, leading to male fertility problems. So far, the assessment of sperm DNA breakage has been challenging because protamines render the nuclear chromatin highly compacted. Here, we report the application of a new test to quantify DNA fragmentation in spermatozoa of an externally fertilizing teleost fish. The sperm chromatin dispersion (SCD) test uses a species-specific lysing solution to generate controlled protein depletion that, followed by DNA-specific fluorescent labelling, allows an easy morphological discrimination between nuclei affected by DNA damage. Using tench (Tinca tinca) as our model, we first trialled the test against established, but more technically demanding, assays employing in situ nick translation (ISNT) and the comet assay. The SCD test showed high concordance with ISNT, comet assay measures and a chromatin-swelling test, confirming the application of this straightforward SCD technique to various aspects of reproductive biology. Second, we examined between-male variation in DNA damage, and measured changes through time following spermatozoal activation. Between-male variation in the basal levels of average DNA damage ranged from 0 to 20% of sperm showing damage, and all showed increases in DNA fragmentation through time (0–60 min). The rates of DNA damage increase are the fastest so far recorded in sperm for a living organism, and may relate to the external fertilization mode. Our findings have relevance for broodstock selection and optimizing IVF protocols routinely used in modern aquaculture.


Zygote ◽  
2012 ◽  
Vol 21 (4) ◽  
pp. 330-336 ◽  
Author(s):  
Adriana Fortunato ◽  
Rita Leo ◽  
Francesca Liguori

SummaryThe integrity of sperm chromatin structure has proven to be of great importance for human fertility. In this study, we investigated whether sperm cryopreservation has an effect on nuclear DNA tertiary structure, (i.e. condensation), measured by aniline blue staining, in 103 male patients who required consultation for hypo-fertility. Sperm DNA damage was significantly higher in patients showing oligospermia and severe morphological abnormalities than in native sperm populations. Furthermore we observed that chromatin decondensation was related to the cryostorage technique and to the duration of storage. This increase in decondensation was highly significant (P < 0.01) immediately after cryopreservation and from 90 days of cryostorage onwards. The possible mechanisms involved in sperm chromatin cryoinjury and the need to incorporate new methods for testing sperm nuclear structure alteration into the routine spermiogram are discussed.


2017 ◽  
Vol 57 (10) ◽  
pp. 1975 ◽  
Author(s):  
Santiago T. Peña, Jr ◽  
Bruce Gummow ◽  
Anthony J. Parker ◽  
Damien B. B. P. Paris

Temperature is a crucial factor in mammalian spermatogenesis. The scrotum, pampiniform plexus, and cremaster and dartos muscles in mammals are specific adaptations to ensure sperm production in a regulated environment 4−6°C below internal body temperature. However, the limited endogenous antioxidant systems inherent in mammalian spermatozoa compounded by the loss of cytosolic repair mechanisms during spermatogenesis, make the DNA in these cells particularly vulnerable to oxidative damage. Boar sperm is likely to be more susceptible to the effects of heat stress and thus oxidative damage due to the relatively high unsaturated fatty acids in the plasma membrane, low antioxidant capacity in boar seminal plasma, and the boar’s non-pendulous scrotum. Heat stress has a significant negative impact on reproductive performance in piggeries, which manifests as summer infertility and results in productivity losses that amount to millions of dollars. This problem is particularly prevalent in tropical and subtropical regions where ambient temperatures rise beyond the animal’s zone of thermal comfort. Based on preliminary studies in the pig and other species, this article discusses whether heat stress could induce sufficient DNA damage in boar sperm to significantly contribute to the high rates of embryo loss and pregnancy failure observed in the sow during summer infertility. Heat stress-induced damage to sperm DNA can lead to disrupted expression of key developmental genes essential for the differentiation of early cell lineages, such as the trophectoderm, and can distort the timely formation of the blastocyst; resulting in a failure of implantation and ultimately pregnancy loss. Confirming such a link would prompt greater emphasis on boar management and strategies to mitigate summer infertility during periods of heat stress.


Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 501 ◽  
Author(s):  
Alexandre Champroux ◽  
Christelle Damon-Soubeyrand ◽  
Chantal Goubely ◽  
Stephanie Bravard ◽  
Joelle Henry-Berger ◽  
...  

Recent studies have revealed a well-defined higher order of chromosome architecture, named chromosome territories, in the human sperm nuclei. The purpose of this work was, first, to investigate the topology of a selected number of chromosomes in murine sperm; second, to evaluate whether sperm DNA damage has any consequence on chromosome architecture. Using fluorescence in situ hybridization, confocal microscopy, and 3D-reconstruction approaches we demonstrate that chromosome positioning in the mouse sperm nucleus is not random. Some chromosomes tend to occupy preferentially discrete positions, while others, such as chromosome 2 in the mouse sperm nucleus are less defined. Using a mouse transgenic model (Gpx5−/−) of sperm nuclear oxidation, we show that oxidative DNA damage does not disrupt chromosome organization. However, when looking at specific nuclear 3D-parameters, we observed that they were significantly affected in the transgenic sperm, compared to the wild-type. Mild reductive DNA challenge confirmed the fragility of the organization of the oxidized sperm nucleus, which may have unforeseen consequences during post-fertilization events. These data suggest that in addition to the sperm DNA fragmentation, which is already known to modify sperm nucleus organization, the more frequent and, to date, the less highly-regarded phenomenon of sperm DNA oxidation also affects sperm chromatin packaging.


2019 ◽  
Author(s):  
Sjors Middelkamp ◽  
Helena T.A. van Tol ◽  
Diana C.J. Spierings ◽  
Sander Boymans ◽  
Victor Guryev ◽  
...  

AbstractGenomic instability is common in early embryo development, but the underlying causes are largely unknown. Here we examined the consequences of sperm DNA damage on the embryonic genome by single-cell genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by radiation. Sperm DNA damage caused fragmentation of chromosomes and segregation errors such as heterogoneic cell divisions yielding a broad spectrum of genomic aberrations that are similar to those frequently found in human embryos. The mosaic aneuploidies, mixoploidy, uniparental disomies and de novo structural variation induced upon sperm DNA damage may compromise health and lead to rare genomic disorders when embryos escape developmental arrest.One Sentence SummaryDNA damage in sperm cells leads to genomic defects in embryos


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Vahidi ◽  
F S Amjadi ◽  
F Kalat. sabz ◽  
Z Zandie ◽  
N Narimani

Abstract Study question Which sperm preparation technique separate the best quality sperm? Summary answer Microfluidic method improved the sperm parameters and decreased sperm DNA damage. What is known already About 40% of infertility issues are due to male factor. One of the known causes of male infertility is associated with low sperm parameters and high level DNA fragmentation. Sperm preparation techniques in ICSI procedures is used in order to obtain the best-quality sperm. Study design, size, duration The present study was designed to compare Microfluidic, Zeta potential, Magnetic Activated Cell Sorting (MACS) and Swim-up methods for sperm preparation and the effect of these methods on semen parameters and sperm DNA integrity in infertile men (n = 25) with a mean age of 38. Participants/materials, setting, methods In this study, each sample was divided into 4 groups, one part for preparing by Microfluidic method, one of them for preparing by Swim -up method, the other one was prepared by MACS and the last one was prepared by zeta potential. Then sperm count, viability, motility and morphology were assessed according to WHO 2010. DNA damage were assessed by Sperm DNA Fragmentation assay and sperm chromatin packaging assessed by CMA3 staining test Main results and the role of chance Sperm parameters including viability, motility, and morphology in the Microfluidic method were significantly improved and sperm DNA damage were significantly lower than three other methods (P-value &lt;0.05). The sperm parameters and sperm DNA damage after preparation by MACS and Zeta potential methods were not significantly different however in the Swim-up method sperm parameters were lower than three other methods (P-value &lt;0.05). Limitations, reasons for caution The fertilization and pregnancy rate of the resulting embryos are not available. Wider implications of the findings: Our results showed that Microfluidic can be an effective way to improve sperm quality of infertile male compared to conventional preparation methods. We also found instead of the MACS method, we can use the Zeta potential method according to their costs, for sperm preparation during ART cycle. Trial registration number *


2020 ◽  
Vol 32 (10) ◽  
pp. 948 ◽  
Author(s):  
Stephen D. Johnston ◽  
Carmen López-Fernández ◽  
Eloise Pappin ◽  
Alexandra Hampe ◽  
Robert Doneley ◽  
...  

Herein we report a simple method for assessing avian sperm DNA fragmentation (SDF) using the sperm chromatin dispersion test (SCDt). The presence of sperm DNA damage was confirmed indirectly by correlating results of the SCDt determined in three bird species with results of a corresponding neutral comet assay (r=0.99; P&lt;0.005). Frozen–thawed spermatozoa of each species were also incubated at 37°C for 5h and the within- and between-species variation of SDF, as an indicator of sperm DNA longevity, examined. The dynamic assessment of SDF using the SCDt revealed species and individual bird (rooster and turkey) differences in sperm DNA longevity.


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