scholarly journals Cytotoxic Effects of Benzene Metabolites on Human Sperm Function: An In Vitro Study

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Priyanka Mandani ◽  
Ketki Desai ◽  
Hyacinth Highland

In recent years, individuals are rampantly exposed to vapours of benzene, through paint, plastic, petroleum industries, fuel exhaust, and tobacco smoke. Hence the present investigation was directed towards determining the effect of benzene metabolites, namely, phenol-hydroquinone and catechol, on the motility, viability, and nuclear integrity of the human spermatozoa. From the results obtained it was clear that exposure to phenol-hydroquinone caused a significant decline in both, sperm motility and viability. Exposure to a phenol-hydroquinone (Phase I) microenvironment may therefore inhibit metabolically active enzymes, thus impeding ATP production, and in turn lowers sperm motility and viability. In addition, the present study also revealed that both metabolites of benzene caused significant denaturation of sperm nuclear DNA. Hence, exposure to phenol-hydroquinone in vitro could have resulted in generation of free radicals and altered membrane function, which is reflected by a decline in the motility, viability, and loss of sperm nuclear DNA integrity. In Phase II, the exposure of human sperm in vitro to varied concentrations of catechol caused only insignificant changes in sperm motility and viability as compared to those observed on exposure to phenol-hydroquinone. Hence, exposure to catechol appeared to have less toxic effects than those of phenol-hydroquinone.

2017 ◽  
Vol 29 (6) ◽  
pp. 1169 ◽  
Author(s):  
Nicola A. Pascarelli ◽  
Antonella Fioravanti ◽  
Elena Moretti ◽  
Giacomo M. Guidelli ◽  
Lucia Mazzi ◽  
...  

Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500 ng mL–1) and etanercept (from 800 µg mL–1 to 2000 µg mL–1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200 µg mL–1, etanercept can block, in a significant way, the toxic effects of TNF-α (500 ng mL–1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.


Andrologia ◽  
2019 ◽  
Vol 51 (6) ◽  
pp. e13260 ◽  
Author(s):  
Saleem Ali Banihani ◽  
Alayna'‐almarddyah Abdullah Al‐khawalde

2020 ◽  
Vol 14 ◽  
pp. 263349412090937
Author(s):  
Huanhuan Hu ◽  
Xiaowei Shi ◽  
Guojie Ji ◽  
Rui Liu ◽  
Jing Zhang ◽  
...  

Rapid freezing and vitrification are becoming popular for sperm freezing in humans; however, basic and critical issues relevant to sperm cryopreservation remain to be resolved. The aims of the present study were to study the effects of osmolality of freezing medium, sperm concentrations, thawing methods, and sugars (sucrose and trehalose) on sperm motility and DNA integrity by rapid freezing using 0.5 ml standard straws loaded with 100 µl sperm each. The results showed that (1) the post-thaw recovery rates of total motility and progressive motility of sperm cryopreserved in freezing medium containing 0.25 M sucrose with 442 mOsm/kg osmolality were significantly higher ( p < 0.05) than that of sperm cryopreserved in freezing medium containing 0.25 M sucrose with 536 mOsm/kg osmolality (36.5 ± 2.8% and 36.9 ± 1.7% versus 30.4 ± 1.9% and 30.3 ± 2.9%, respectively), (2) cryopreservation of both total and progressive motilities was not significantly affected ( p > 0.05) by sperm concentrations in the range from 5 to 20 × 106 sperm/ml, (3) thawing method 37°C for 2 min was better than 42°C for 15 s in terms of post-thaw recovery rates of both total and progressive motilities ( p < 0.05), (4) 0.25 M trehalose was better than 0.25 M sucrose in cryopreserving both total and progressive motilities ( p < 0.05), and (5) sperm nuclear DNA is relatively resistant to the changes of the above factors compared with sperm motility. It was concluded that human sperm can be best cryopreserved by rapid freezing using 0.25 M sucrose or trehalose with osmolality 442 to 457 mOsm/kg at high sperm concentration followed by thawing at 37°C. Trehalose is a stronger cryoprotectant than sucrose for sperm cryopreservation.


2021 ◽  
Author(s):  
M J Campbell ◽  
I E Sucquart ◽  
A Whittaker ◽  
H J Sanganee ◽  
C L R Barratt ◽  
...  

Abstract STUDY QUESTION Does AZD5904, a myeloperoxidase inhibitor (MPOi), have any effect on human sperm function in vitro? SUMMARY ANSWER AZD5904 improves sperm function in an in vitro model of oxidative stress (OS) and potentially offers a novel treatment approach for male infertility. WHAT IS KNOWN ALREADY Male infertility is an underlying or contributory cause in half of all couples experiencing difficulties conceiving, yet there is currently no effective treatment or cure. OS is a common pathology in a significant proportion of infertile men. It can negatively affect sperm motility and the ability to fertilize a mature oocyte, as well as DNA integrity, and therefore represents an attractive target for therapeutic intervention. STUDY DESIGN, SIZE, DURATION This study included population-based samples from men (23–50 years) attending Ninewells Assisted Conception Unit, Dundee for diagnostic semen analysis, July 2017–September 2018. Semen samples (n = 47) from 45 patients were used. PARTICIPANTS/MATERIALS, SETTING, METHODS Neutrophils activated using zymosan were incubated with prepared human spermatozoa for 2 h (T2) and 24 h (T24) to create an in vitro model of OS. Parallel samples were co-incubated with AZD5904, an MPOi, to examine its effects. Sperm motility was assessed by computer-assisted sperm analysis at T2 and T24. Functional motility was assessed by sperm penetration assay. Statistical analysis was performed using GraphPad Prism. MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in total or progressive sperm motility between any treatment and control groups at T2 or T24. Nonetheless, significant positive effects on sperm function were observed with AZD5904, with 16/45 (35.6%) samples (with both normal and abnormal baseline semen analysis characteristics) displaying a ≥20% increase in sperm penetrated through viscous media (P &lt; 0.003). LIMITATIONS, REASONS FOR CAUTION This was an in vitro study. WIDER IMPLICATIONS OF THE FINDINGS Treatment with AZD5904 resulted in significant increased sperm penetration in one of three samples treated, which is likely to represent improvement in sperm function required for fertilization. We are now planning a clinical trial to validate these results and hope that this could represent a new treatment for male infertility. STUDY FUNDING/COMPETING INTEREST(S) AZD5904 was shared through the AstraZeneca Open Innovation program. The study was funded by AstraZeneca and sponsored by the University of Dundee. Additional funding was provided by Chief Scientist Office/NHS Research Scotland (S.J.M.d.S.). A.W. and H.J.S. are both full time employees of AstraZeneca. A.W. and H.J.S. are inventors on a patent filed by AstraZeneca titled MPOi for use in medicine which includes MPOi for use in the treatment of male infertility (WO 2019/016074 Al). S.J.M.d.S. is Associate Editor of Human Reproduction and Editorial Board member of Reproduction & Fertility. C.L.R.B. is Editor of RBMO and has received lecturing fees from Merck and Ferring and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B. was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012–2016). C.L.R.B. has a patent WO2013054111 A1 issued. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 744
Author(s):  
Daria Noto ◽  
Giulia Collodel ◽  
Daniela Cerretani ◽  
Cinzia Signorini ◽  
Laura Gambera ◽  
...  

The study evaluated the chlorogenic acid (CGA) antioxidant potential on oxidative stress (OS) induced in vitro in human spermatozoa and during cryopreservation procedure. Swim-up selected spermatozoa were treated with 100 µM CGA, 100 µM H2O2 to induce lipid peroxidation (LPO), and with both compounds and the effects on mitochondrial membrane potential (MMP) by JC-1, DNA integrity by acridine orange (AO), and sperm ultrastructure by transmission electron microscopy (TEM), were evaluated. CGA antioxidant activity was assessed by measuring malondialdehyde (MDA) and F2-isoprostanes (F2-IsoPs) in the media. The CGA protective activity and the immunolocalization of Phospho-AMPKα (Thr172) were explored in frozen-thawed sperm. CGA was not toxic for sperm motility, DNA integrity and MMP. The increase in MDA (p < 0.05) and F2-IsoPs (p < 0.001), DNA damage (p < 0.01) and low MMP (p < 0.01) levels after H2O2 treatment were reduced in presence of CGA as well as the percentage of broken plasma membranes (p < 0.01) and altered acrosomes (p < 0.01) detected by TEM. Treated frozen-thawed spermatozoa showed increased sperm motility (p < 0.01), DNA integrity (p < 0.01), MMP (p < 0.01), reduced MDA (p < 0.01) and increased sperm percentage with Phospho-AMPKα labelling in the head (p < 0.001). CGA can be used to supplement culture media during semen handling and cryopreservation where OS is exacerbated.


2006 ◽  
Vol 37 (7) ◽  
pp. 840-843 ◽  
Author(s):  
Osman Erogul ◽  
Emin Oztas ◽  
Ibrahim Yildirim ◽  
Tayfun Kir ◽  
Emin Aydur ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Rahban ◽  
A Rehfeld ◽  
C Schiffer ◽  
C Brenker ◽  
D. Louise Egeberg Palme ◽  
...  

Abstract Study question Do Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants affect the function of human sperm? Summary answer The SSRI-antidepressant Sertraline (e.g. Zoloft) inhibits the sperm-specific Ca2+ channel CatSper and affects human sperm function in vitro. What is known already In human sperm, CatSper translates changes of the chemical microenvironment into changes of the intracellular Ca2+ concentration ([Ca2+]i) and swimming behavior. CatSper is promiscuously activated by oviductal ligands, but also by synthetic chemicals that might disturb the fertilization process. It is well known that SSRIs have off-target actions on Ca2+, Na+, and K+ channels in somatic cells. Whether SSRIs affect the activity of CatSper is, however, unknown. Study design, size, duration We studied the action of the seven drugs belonging to the most commonly prescribed class of antidepressants, SSRIs, on resting [Ca2+]i and Ca2+ influx via CatSper in human sperm. The SSRI Sertraline was selected for in-depth analysis of its action on steroid-, prostaglandin-, pH-, and voltage-activation of human CatSper. Moreover, the action of Sertraline on sperm acrosomal exocytosis and penetration into viscous media was evaluated. Participants/materials, setting, methods The activity of CatSper was investigated in sperm of healthy volunteers, using kinetic Ca2+ fluorimetry and patch-clamp recordings. Acrosomal exocytosis was investigated using Pisum sativum agglutinin (PSA) and image cytometry. Sperm penetration in viscous media was evaluated using the Kremer test. Main results and the role of chance Four SSRIs increased [Ca2+]i, two out of which also attenuated ligand-induced Ca2+ influx via CatSper. In contrast, Sertraline decreased [Ca2+]i and almost completely suppressed ligand-induced Ca2+ influx via CatSper. Remarkably, the drug was about four-fold more potent to suppress prostaglandin- versus steroid-induced Ca2+ influx. Sertraline also suppressed alkaline- and voltage-activation of CatSper, indicating that the drug directly inhibits human CatSper. Finally, Sertraline suppressed ligand-induced acrosome reaction and sperm penetration into viscous media. Limitations, reasons for caution This is an in vitro study. Future studies have to assess the physiological relevance in vivo. Wider implications of the findings The off-target action of Sertraline on CatSper in human sperm might impair the fertilization process. In a research setting, Sertraline may be used to selectively inhibit prostaglandin-induced Ca2+ influx. Trial registration number CRU326


2018 ◽  
Vol 295 ◽  
pp. S141
Author(s):  
M.G. Hinojosa ◽  
D. Gutierrez-Praena ◽  
A.I. Prieto ◽  
L. Espinar-López ◽  
A.M. Cameán ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document