Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.
- MeSH
- endokrinní disruptory farmakologie toxicita MeSH
- epigeneze genetická * účinky léků MeSH
- ethinylestradiol * farmakologie MeSH
- histony * metabolismus MeSH
- myši MeSH
- posttranslační úpravy proteinů účinky léků MeSH
- protaminy * metabolismus genetika MeSH
- spermatogeneze * účinky léků genetika MeSH
- spermie účinky léků metabolismus MeSH
- testis * účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that belongs to the group of gasotransmitters along with nitric oxide (NO) and carbon monoxide (CO). H2S plays a pivotal role in male reproductive processes. It is produced in various tissues and cells of the male reproductive system, including testicular tissue, Leydig and Sertoli cells, epididymis, seminal plasma, prostate, penile tissues, and sperm cells. This review aims to summarize the knowledge about the presence and effects of H2S in male reproductive tissues and outline possible therapeutic strategies in pathological conditions related to male fertility, e. g. spermatogenetic disorders and erectile dysfunction (ED). For instance, H2S supports spermatogenesis by maintaining the integrity of the blood-testicular barrier (BTB), stimulating testosterone production, and providing cytoprotective effects. In spermatozoa, H2S modulates sperm motility, promotes sperm maturation, capacitation, and acrosome reaction, and has significant cytoprotective effects. Given its vasorelaxant effects, it supports the erection of penile tissue. These findings suggest the importance and therapeutic potential of H2S in male reproduction, paving the way for further research and potential clinical applications.
- MeSH
- erektilní dysfunkce farmakoterapie metabolismus MeSH
- lidé MeSH
- mužská infertilita metabolismus farmakoterapie MeSH
- mužské pohlavní orgány metabolismus účinky léků MeSH
- rozmnožování * účinky léků fyziologie MeSH
- spermatogeneze * účinky léků MeSH
- spermie účinky léků metabolismus MeSH
- sulfan * metabolismus farmakologie MeSH
- testis metabolismus účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Asistovaná reprodukcia je pomerne rýchlo sa rozvíjajúci odbor medicíny, ktorý poskytuje liečbu neplodným párom. Od narodenia prvého dieťaťa zo „skúmavky“ uplynulo viac než 45 rokov, za ktoré obdobie boli vyvinuté rôzne metodiky za účelom zvýšenia úspešnosti liečby. Samotná spontánna koncepcia je podmienená mnohými faktormi, o ktorých máme aj v súčasnosti pomerne málo informácií. Vývoj asistovanej reprodukcie postupne odhaľuje jednotlivé významné procesy a stavy ktoré ovplyvňujú vznik a vývoj úspešnej tehotnosti. Diabetes mellitus a s ním spojené metabolické poruchy majú negatívny vplyv na kvalitu pohlavných buniek, fertilizáciu, nidáciu a vývoj tehotnosti. Identifikácia a úspešná liečba diabetu má preto dôležitý význam pred zahájením liečby neplodnosti.
Assisted reproduction is a relatively rapidly developing field of medicine focused on the treatment of infertile couples. More than 45 years have passed since the birth of the first “test- tube baby”. Since that time various methods were developed to increase the success rate of the treatment. Spontaneous conception itself is conditioned by many factors, about which we still have relatively little information. The development of assisted reproduction techniques gradually reveals important processes and conditions that influence the development of a successful pregnancy. Diabetes mellitus and associated metabolic disorders have a negative impact on the quality of gametes, fertilization as well as the development of pregnancy. Identification and successful treatment of diabetes plays a key role before starting infertility treatment.
- MeSH
- asistovaná reprodukce MeSH
- diabetes mellitus MeSH
- erektilní dysfunkce etiologie terapie MeSH
- fertilizace in vitro metody MeSH
- komplikace diabetu * prevence a kontrola MeSH
- lidé MeSH
- menstruační cyklus MeSH
- mužská infertilita diagnóza etiologie terapie MeSH
- oocyty MeSH
- spermatogeneze MeSH
- syndrom polycystických ovarií diagnóza komplikace terapie MeSH
- ženská infertilita diagnóza etiologie terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling has fundamental roles in the regulation of the stem cell niche for both embryonic and adult stem cells. In zebrafish, male germ stem cell niche is regulated by follicle-stimulating hormone (Fsh) through different members of the TGF-β superfamily. On the other hand, the specific roles of TGF-β and BMP signaling pathways are unknown in the zebrafish male germ stem cell niche. Considering this lack of information, the present study aimed to investigate the pharmacological inhibition of TGF-β (A83-01) and BMP (DMH1) signaling pathways in the presence of recombinant zebrafish Fsh using testicular explants. We also reanalyzed single cell-RNA sequencing (sc-RNA-seq) dataset from adult zebrafish testes to identify the testicular cellular sites of smad expression, and to understand the physiological significance of the changes in smad transcript levels after inhibition of TGF-β or BMP pathways. Our results showed that A83-01 potentiated the pro-stimulatory effects of Fsh on spermatogonial differentiation leading to an increase in the proportion area occupied by differentiated spermatogonia with concomitant reduction of type A undifferentiated (Aund) spermatogonia. In agreement, expression analysis showed lower mRNA levels for the pluripotency gene pou5f3, and increased expression of dazl (marker of type B spermatogonia and spermatocyte) and igf3 (pro-stimulatory growth factor) following the co-treatment with TGF-β inhibitor and Fsh. Contrariwise, the inhibition of BMP signaling nullified the pro-stimulatory effects of Fsh, resulting in a reduction of differentiated spermatogonia and increased proportion area occupied by type Aund spermatogonia. Supporting this evidence, BMP signaling inhibition increased the mRNA levels of pluripotency genes nanog and pou5f3, and decreased dazl levels when compared to control. The sc-RNA-seq data unveiled a distinctive pattern of smad expression among testicular cells, primarily observed in spermatogonia (smad 2, 3a, 3b, 8), spermatocytes (smad 2, 3a, 8), Sertoli cells (smad 1, 3a, 3b), and Leydig cells (smad 1, 2). This finding supports the notion that inhibition of TGF-β and BMP signaling pathways may predominantly impact cellular components within the spermatogonial niche, namely spermatogonia, Sertoli, and Leydig cells. In conclusion, our study demonstrated that TGF-β and BMP signaling pathways exert antagonistic roles in the zebrafish germ stem cell niche. The members of the TGF-β subfamily are mainly involved in maintaining the undifferentiated state of spermatogonia, while the BMP subfamily promotes spermatogonial differentiation. Therefore, in the complex regulation of the germ stem cell niche by Fsh, members of the BMP subfamily (pro-differentiation) should be more predominant in the niche than those belonging to the TGF-β (anti-differentiation). Overall, these findings are not only relevant for understanding the regulation of germ stem cell niche but may also be useful for expanding in vitro the number of undifferentiated spermatogonia more efficiently than using recombinant hormones or growth factors.
- MeSH
- buněčná diferenciace genetika MeSH
- dánio pruhované * genetika MeSH
- folikuly stimulující hormon farmakologie metabolismus MeSH
- messenger RNA genetika MeSH
- pyrazoly * MeSH
- spermatogeneze genetika MeSH
- spermatogonie * metabolismus MeSH
- testis metabolismus MeSH
- thiosemikarbazony * MeSH
- transformující růstový faktor beta metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- infertilita * etiologie prevence a kontrola MeSH
- lidé MeSH
- nemoci dělohy komplikace patologie MeSH
- nemoci ovaria etiologie komplikace MeSH
- nemoci vejcovodů diagnóza komplikace MeSH
- reprodukční zdraví * MeSH
- rizikové faktory MeSH
- spermatogeneze MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- asistovaná reprodukce klasifikace MeSH
- hormon uvolňující gonadotropiny analogy a deriváty terapeutické užití MeSH
- infertilita * etiologie terapie MeSH
- kryoprezervace klasifikace metody MeSH
- lidé MeSH
- nádory * komplikace MeSH
- nakládání s embryem dějiny MeSH
- ovariální rezerva MeSH
- spermatogeneze účinky léků MeSH
- uchování spermatu metody MeSH
- vitrifikace MeSH
- zachování plodnosti MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Ostřížková S, Zlotkowska R. Vliv onemocnění covid-19 na mužskou plodnost. Onemocnění covid-19 se od roku 2019 rychle rozšířilo napříč kontinenty a způsobilo pandemii. Častější výskyt tohoto onemocnění byl pozorován u mužů, částečně vlivem vyšší exprese angiotenzin‐konvertujícího enzymu 2 (ACE2), který, společně s transmembránovou serinovou proteázou 2 (TMPRSS2), hraje významnou roli v průniku viru do buňky. ACE2 i TMPRSS2 jsou exprimovány na povrchu mnoha lidských tkání včetně tkání reprodukčního systému mužů i žen. Z tohoto důvodu je stále zkoumán vliv viru SARS‐CoV-2 na mužskou plodnost. Proběhlé studie se zabývají zejména histopatologickými změnami u post mortem vzorků z varlat covid-19 pozitivních pacientů, ale také imunitními reakcemi indukovanými virem SARS-CoV-2. Negativní dopad může mít cytokinová bouře způsobená pyroptózou buněk a oxidační stres. Jelikož je většina virů, včetně SARS‐CoV-2, schopna prolomit hematoencefalickou bariéru, může dojít k ovlivnění hypotalamo‐hypofýzo‐gonádové osy nezbytné pro endokrinní regulaci spermatogeneze. Pacienti s onemocněním covid-19 vykazují vyšší hladiny luteinizačního hormonu a prolaktinu a nižší hladiny testosteronu vlivem poškození Leydigových buněk. Hodnocení parametrů spermiogramu poukázalo na zhoršení celkové motility spermií a snížení koncentrace spermií v ejakulátu. Ovlivnění parametrů spermiogramu se však zdá být dočasné.
Ostřížková S, Zlotkowska R. The effect of covid-19 on male fertility. Covid-19 disease has spread rapidly across continents since 2019, causing a pandemic. A higher prevalence of the disease has been observed in males, partly due to higher expression of angiotensin-converting enzyme 2 (ACE2), which, together with transmembrane serine protease 2 (TMPRSS2), plays an important role in viral entry into the cell. Both ACE2 and TMPRSS2 are expressed on the surface of many human tissues, including tissues of the male and female reproductive system. For this reason, the effect of SARS-CoV-2 on male fertility is still under investigation. Current studies have focused on histopathological changes in post mortem testicular samples from covid-19 positive patients, but also on immune responses induced by SARS-CoV-2. Cytokine storm caused by cell pyroptosis and oxidative stress may have a negative impact. As most viruses, including SARS-CoV-2, are able to break the bloodbrain barrier, the hypothalamic-pituitary-gonadal axis, essential for endocrine regulation of spermatogenesis, may also be affected. Patients with covid-19 disease show higher levels of luteinizing hormone and prolactin and lower levels of testosterone due to Leydig cell damage. Sperm analysis showed a deterioration of total sperm motility and a decrease in sperm concentration in the ejaculate. However, the effect on spermiogram parameters appears to be temporary.
- MeSH
- analýza spermatu MeSH
- angiotensin-konvertující enzym 2 MeSH
- COVID-19 * komplikace MeSH
- fertilita * MeSH
- hormony MeSH
- imunita MeSH
- lidé MeSH
- mužská infertilita etiologie MeSH
- oxidační stres MeSH
- prostata MeSH
- spermatogeneze MeSH
- testis anatomie a histologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Male germ cells experience a drastic chromatin remodeling through the nucleo-histone to nucleo-protamine (NH-NP) transition necessary for proper sperm functionality. Post-translational modifications (PTMs) of H4 Lys5, such as acetylation (H4K5ac), play a crucial role in epigenetic control of nucleosome disassembly facilitating protamine incorporation into paternal DNA. It has been shown that butyrylation on the same residue (H4K5bu) participates in temporal regulation of NH-NP transition in mice, delaying the bromodomain testis specific protein (BRDT)-dependent nucleosome disassembly and potentially marking retained nucleosomes. However, no information was available so far on this modification in human sperm. Here, we report a dual behavior of H4K5bu and H4K5ac in human normal spermatogenesis, suggesting a specific role of H4K5bu during spermatid elongation, coexisting with H4K5ac although with different starting points. This pattern is stable under different testicular pathologies, suggesting a highly conserved function of these modifications. Despite a drastic decrease of both PTMs in condensed spermatids, they are retained in ejaculated sperm, with 30% of non-colocalizing nucleosome clusters, which could reflect differential paternal genome retention. Whereas no apparent effect of these PTMs was observed associated with sperm quality, their presence in mature sperm could entail a potential role in the zygote.
- MeSH
- acetylace MeSH
- chromatin * metabolismus MeSH
- histony metabolismus MeSH
- lidé MeSH
- myši MeSH
- nukleozomy * metabolismus MeSH
- posttranslační úpravy proteinů MeSH
- protaminy metabolismus MeSH
- restrukturace chromatinu MeSH
- sperma metabolismus MeSH
- spermatidy metabolismus MeSH
- spermatogeneze fyziologie MeSH
- spermie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cíl studie: Cílem práce je shrnutí současných poznatků o možnostech léčby poruch plodnosti u pacientů s Klinefelterovým syndromem. Metodika: Rešerše literatury publikované v databázích WoS, Scopus, PubMed/Medline do listopadu 2021. Text: Klinefelterův syndrom je chromozomální aberací způsobenou přítomností nadpočetného chromozomu X u muže. K významným klinickým aspektům patří mužská sterilita podmíněná těžkou poruchou spermatogeneze. V současné době přibývá nových poznatků o možnostech léčby poruch plodnosti u mužů s tímto onemocněním. Závěr: Mezioborová spolupráce umožňuje včasnou diagnostiku a léčbu Klinefelterova syndromu. Asistovaná reprodukce má nezastupitelnou úlohu pro léčbu poruch plodnosti pacientů s Klinefelterovým syndromem.
Objective: The goal of this article is to present the current knowledge of Klinefelter syndrome and its impact on male reproductive function as well as the current treatment options. Methods: PubMed/Medline, WoS and Scopus were searched for articles indexed until November 2021. Text: Klinefelter syndrome is a chromosomal aberration with an additional X chromosome in males. This may adversely affect testicular growth and spermatogenesis, thus resulting in male infertility. Recently, new knowledge has appeared about the treatment of male infertility. Conclusion: Interdisciplinary approach enables early diagnosis and treatment of patients with Klinefelter syndrome. Assisted reproductive technology is essential for infertility treatment in patients with Klinefelter syndrome.
- MeSH
- aneuploidie MeSH
- Klinefelterův syndrom * diagnóza genetika MeSH
- lidé MeSH
- mužská infertilita MeSH
- spermatogeneze MeSH
- testis fyziologie patofyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Male reproductive functions are an important area affecting men ́s overall health and well-being. However, during the last years, there has been observed increasing incidence of male reproductive issues. The radical growth has been recorded parallelly with a massive expanse of industrialization and agricultural chemigation. Many groups of experts have begun to identify several potential factors and substances that may have adverse effects on men ́s reproductive health. Since then, xenobiotics have become a major concern of many scientific studies. There is evidence that most of them have multigenerational and transgenerational effects on reproductive health, which is a serious problem for our population. Bisphenol A could be considered as one of the most studied endocrine disruptors. Until now, several negative effects of bisphenol A were associated with reduced weight testes, histological alterations, impairment spermatogenesis, and steroidogenesis as well as with testes or prostate cancer. Due to convincing evidence, bisphenol A has been started to replace by its analogues such as bisphenol B, S, F, in order to eliminate and suppress the risk of exposure to bisphenol A. However, it seems that a lack of toxicological analyses allows using of these hazardous substances in daily life. Their harmful effect was confirmed by the animal in vitro and in vivo models, while the epidemiological studies monitoring the impact of bisphenol analogues on men's reproductive health are markedly limited. This review provides information about the effects of bisphenol on reproductive health in men. At the same time, it is focused on physiological aspects of sperm viability, steroid hormone secretion, sperm motility, or testes histology in relation to bisphenols exposure.
- MeSH
- benzhydrylové sloučeniny toxicita MeSH
- endokrinní disruptory * toxicita MeSH
- fenoly MeSH
- lidé MeSH
- motilita spermií * MeSH
- spermatogeneze MeSH
- testis MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH