scholarly journals EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner

2018 ◽  
Vol 7 (1) ◽  
pp. 16-25 ◽  
Author(s):  
A Rehfeld ◽  
D L Egeberg ◽  
K Almstrup ◽  
J H Petersen ◽  
S Dissing ◽  
...  
Keyword(s):  
Acrosome Reaction ◽  
Cell Function ◽  
Human Sperm ◽  
Cumulus Cells ◽  
Viscous Medium ◽  
Sperm Function ◽  
Sperm Cells ◽  
Uv Filters ◽  
Sperm Penetration

Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca2+ influx through CatSper, thus mimicking the effect of progesterone on Ca2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo.

scholarly journals Expression and function of ras proto-oncogene proteins in human sperm cells

1992 ◽  
Vol 102 (3) ◽  
pp. 487-494 ◽  
Author(s):  
R.K. Naz ◽  
K. Ahmad ◽  
P. Kaplan
Keyword(s):  
Sperm Cell ◽  
Acrosome Reaction ◽  
Cell Function ◽  
Beat Frequency ◽  
Human Sperm ◽  
Sperm Cells ◽  
Ras Protein ◽  
Head Displacement ◽  
Sperm Penetration ◽  
And Function

The presence and role of c-ras proteins were investigated in mature human sperm cells. The v-H-ras monoclonal antibody (mAb) against the c-ras protein, p21, reacted specifically with the acrosomal region of methanol-fixed as well as unfixed-live capacitated and non-capacitated human sperm cell in the indirect immunofluorescence technique. The v-H-ras mAb predominantly recognized c-ras protein of 21 kDa on the Western blot of lithium diiodosalicylate (LIS)-solubilized human sperm preparation. The incubation of sperm cells with v-H-ras mAb affected the sperm cell function in the human sperm penetration assay. The antibody significantly reduced the acrosome reaction and release of acrosin activity from the sperm cells. There was no effect of the mAb on percentage motility, although the mAb significantly affected various motility characteristics such as linearity, amplitude of lateral head displacement (ALH) and beat frequency, the motility parameters involved in the hyperactivation phenomenon of sperm cells leading to capacitation and acrosome reaction. These results suggest that the c-ras or c-ras-like proteins are present in mature sperm cell and may have a role in capacitation and/or acrosome reaction of human sperm cell.

Finasteride interferes with prostaglandin-induced CatSper signalling in human sperm

Reproduction ◽  
2021 ◽  
Vol 161 (5) ◽  
pp. 561-572
Author(s):  
Michala Rosa Birch ◽  
Steen Dissing ◽  
Niels E Skakkebæk ◽  
Anders Rehfeld
Keyword(s):  
Acrosome Reaction ◽  
Endocrine Disrupting Chemicals ◽  
Human Sperm ◽  
Viscous Medium ◽  
Single Cell Imaging ◽  
Multiple Binding Sites ◽  
Transient Rise ◽  
Multiple Binding ◽  
Sperm Penetration ◽  
A Minor

Ca2+ signalling controls human sperm functions necessary for successful fertilization. Multiple endocrine-disrupting chemicals have been found to activate the CatSper Ca2+ channel and thereby interfering with Ca2+ signalling in human sperm. Finasteride is prescribed to men in the fertile age to treat hair loss and its use has been associated with impaired male fertility. Due to the structural relatedness of finasteride to the endogenous CatSper ligand progesterone, this study aimed to investigate whether finasteride affects human sperm in a progestogen-like manner. The effect of finasteride on Ca2+ signalling via CatSper in human sperm was investigated in cell suspensions by single-cell imaging. Additionally, effects on sperm penetration into viscous medium and acrosome reaction were assessed. Finasteride alone caused a minor transient rise in the intracellular, free Ca2+ concentration ([Ca2+]i) at physiologically relevant concentrations. Ca2+ signals induced by PGE1 were inhibited by finasteride displaying mixed type of inhibition consistent with multiple binding sites. Finasteride did not interfere with progesterone-induced Ca2+ signalling and no effect on acrosome reaction or sperm viability was found. Finasteride significantly decreased PGE1-induced penetration into viscous medium but in concentrations above what is measured in blood and seminal fluids during regular finasteride administration. In conclusion, the use of finasteride may affect Ca2+ signalling in human sperm through an interaction with the PGE1-binding site, but to which extend it alters the chances of a successful fertilization needs further investigation. It remains to be investigated whether finasteride administration may give rise to side effects by interfering with prostaglandin signalling elsewhere in the human body.

scholarly journals PACAP-mediated sperm–cumulus cell interaction promotes fertilization

Reproduction ◽  
2011 ◽  
Vol 141 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Ichiro Tanii ◽  
Tadashi Aradate ◽  
Kouhei Matsuda ◽  
Akira Komiya ◽  
Hideki Fuse
Keyword(s):  
Sperm Motility ◽  
Acrosome Reaction ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Cell Interaction ◽  
Fertilization Rate ◽  
Type I ◽  
Dependent Manner ◽  
Sperm Penetration

The developing acrosome in spermatids contains pituitary adenylate cyclase-activating polypeptide (PACAP). However, the role of the acrosomal PACAP remains unclear because it has not been detected in mature spermatids and sperm. We reinvestigated whether the sperm acrosome contains PACAP. An antiserum produced against PACAP reacted to the anterior acrosome in epididymal sperm fixed under mild conditions, suggesting that PACAP acts on oocytes and/or cumulus cells at the site of fertilization. Immunolabeling and RT-PCR demonstrated the presence of PACAP type I receptor, a PACAP-specific receptor, in postovulatory cumulus cells. To investigate the role of PACAP in fertilization, we pretreated cumulus–oocyte complexes with the polypeptide. At a low concentration of sperm, the fertilization rate was significantly enhanced by PACAP in a dose-dependent manner. Sperm penetration through the oocyte investment, cumulus layer, and zona pellucida was also enhanced by PACAP. The enhancement was probably due to an enhancement in sperm motility and the zona-induced acrosome reaction, which were stimulated by a cumulus cell-releasing factor. Indeed, PACAP treatment increased the secretion of progesterone from the cumulus–oocyte complexes. These results strongly suggest that in response to PACAP, cumulus cells release a soluble factor that probably stimulates sperm motility and the acrosome reaction, thereby promoting fertilization.

O-228 The SSRI antidepressant Sertraline inhibits CatSper calcium channels in human sperm

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Rahban ◽  
A Rehfeld ◽  
C Schiffer ◽  
C Brenker ◽  
D. Louise Egeberg Palme ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Human Sperm ◽  
Fertilization Process ◽  
Acrosomal Exocytosis ◽  
Depth Analysis ◽  
Sperm Penetration ◽  
Viscous Media ◽  
Voltage Activation

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

scholarly journals Chemical UV Filters Mimic the Effect of Progesterone on Ca2+ Signaling in Human Sperm Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 4297-4308 ◽  
Author(s):  
A. Rehfeld ◽  
S. Dissing ◽  
N. E. Skakkebæk
Keyword(s):  
Human Sperm ◽  
Sperm Cells ◽  
Uv Filters

scholarly journals Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4231
Author(s):  
Xiatian Li ◽  
Tao Luo ◽  
Hua Li ◽  
Nianlong Yan
Keyword(s):  
Signaling Pathways ◽  
Sperm Motility ◽  
Acrosome Reaction ◽  
Caspase 3 ◽  
Human Sperm ◽  
Erk Signaling ◽  
Sperm Function ◽  
Sphingomyelin Synthase ◽  
Protein Levels ◽  
Penetration Ability

Sphingomylin participates in sperm function in animals, and also regulates the Akt and ERK signaling pathways, both of which are associated with the asthenospermia. Sphingomyelin synthase 2 (SMS2) is involved in the biosynthesis of sphingomylin. To determine the relationship between SMS2 and human sperm function, we analyzed the distribution of SMS2 in human sperm and testes, and SMS2 expression in patients with asthenospermia and normozoospermia; human sperm were treated with anti-SMS2, and the sperm motility, penetration ability into methylcellulose, capacitation and acrosome reaction, and sperm [Ca2+]i imaging were evaluated, while the Akt and ERK pathway and cleaved caspase 3 were also analyzed. Results showed that SMS2 was localized in the testis and human sperm, and the protein levels of normozoospermia were higher than asthenospermia. Inhibition of SMS2 activity significantly decreased sperm motility and penetration ability into methylcellulose, but had no influence on capacitation and acrosome reaction, or on intracellular [Ca2+]i compared to IgG-treated control groups. Moreover, the phosphorylation level of Akt was decreased, whereas the phosphorylation of ERK and cleaved-caspase 3 levels were significantly increased. Taken together, SMS2 can affect sperm motility and penetration ability into methylcellulose, and participate in apoptosis associated with the Akt and ERK signaling pathways.

The effects in vitro of TNF-α and its antagonist ‘etanercept’ on ejaculated human sperm

2017 ◽  
Vol 29 (6) ◽  
pp. 1169 ◽  
Author(s):  
Nicola A. Pascarelli ◽  
Antonella Fioravanti ◽  
Elena Moretti ◽  
Giacomo M. Guidelli ◽  
Lucia Mazzi ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
In Vitro Study ◽  
Human Sperm ◽  
Dna Integrity ◽  
Sperm Function ◽  
Sperm Viability ◽  
Tnf Α ◽  
The Impact

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.

Ultrastructural observations on in vivo fertilisation in the brushtail possum, Trichosurus vulpecula, following PMSG/LH superovulation and artificial insemination

Zygote ◽  
1999 ◽  
Vol 7 (4) ◽  
pp. 307-320 ◽  
Author(s):  
M.K. Jungnickel ◽  
A.J. Harman ◽  
J.C. Rodger
Keyword(s):  
Artificial Insemination ◽  
Acrosome Reaction ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Chromatin Decondensation ◽  
Large Hole ◽  
Enzymatic Action ◽  
Acrosomal Membrane ◽  
Sperm Penetration

Information on the dynamics of gamete interaction in marsupials is very limited and not available for any species from the major Australian Order Diprotodontia which includes most of the more familiar animals such as kangaroos, possums and the koala. This study addressed this deficiency by examining the ultrastructure of in vivo fertilised eggs from common brushtail possums (Trichosurus vulpecula). Females were superovulated by treatment with 15 IU PMSG and then 4 mg porcine LH 3 days later, and inseminations were performed 910-13 h after LH) using epididymal spermatozoa. Between 33 and 39 h after LH injection females were killed, reproductive tracts excised and the oviduct ampulla segment flushed for eggs. Three of the six eggs examined were fertilised as judged by the presence of sperm remnants in the cytoplasm. On the basis of these eggs it was found that sperm penetration left a large hole in the zona pellucida (ZP), suggesting that sperm zona penetration occurs primarily by the enzymatic action of acrosomal enzymes. Sperm lying within the perivitelline space were lacking both an outer acrosomal membrane and the associated acrosomal contents, while both these structures were found on sperm embedded within the mucoid layer, which is consistent with induction of the acrosome reaction by binding to the ZP. Once inside the egg cytoplasm, the sperm head travelled only a short distance before chromatin decondensation occurred. Fertilised eggs showed signs of cytoplasmic activation including cytoskeleton association with apparently dividing mitochondria and prominent rough endoplasmic reticulum. Unfertilised eggs appeared to be undergoing degenerative changes and lacked any evidence of activation. This study has demonstrated that superovulation and laparoscopic intravaginal artificial insemination provide a system through which perifertilisation events in the possum and other monovular Australian marsupials can be examined experimentally.

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