Bisphenol S (BPS), the main replacement for bisphenol A (BPA), is thought to be toxic, but limited information is available on the effects of Bisphenol S on ovarian follicles. In our study, we demonstrated the presence of Bisphenol S in the follicular fluid of women at a concentration of 22.4 nM. The effect of such concentrations of Bisphenol S on oocyte maturation and subsequent embryo development is still unknown. Therefore, we focused on the effect of Bisphenol S on in vitro oocyte maturation, fertilization, and embryo development. As a model, we used porcine oocytes, which show many physiological similarities to human oocytes. Oocytes were exposed to Bisphenol S concentrations similar to those detected in female patients in the ART clinic. We found a decreased ability of oocytes to successfully complete meiotic maturation. Mature oocytes showed an increased frequency of meiotic spindle abnormalities and chromosome misalignment. Alarming associations of oocyte Bisphenol S exposure with the occurrence of aneuploidy and changes in the distribution of mitochondria and mitochondrial proteins were demonstrated for the first time. However, the number and quality of blastocysts derived from oocytes that successfully completed meiotic maturation under the influence of Bisphenol S was not affected.

• Publikační typ
• časopisecké články MeSH

Persulfidation contributes to a group of redox post-translational modifications (PTMs), which arise exclusively on the sulfhydryl group of cysteine as a result of hydrogen sulfide (H2S) action. Redox-active molecules, including H2S, contribute to sperm development; therefore, redox PTMs represent an extremely important signalling pathway in sperm life. In this path, persulfidation prevents protein damage caused by irreversible cysteine hyperoxidation and thus maintains this signalling pathway. In our study, we detected both H2S and its production by all H2S-releasing enzymes (cystathionine γ-lyase (CTH), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MPST)) in male reproduction, including spermatozoa. We provided evidence that sperm H2S leads to persulfidation of proteins, such as glyceraldehyde-3-phosphate dehydrogenase, tubulin, and anchor protein A-kinase. Overall, this study suggests that persulfidation, as a part of the redox signalling pathway, is tightly regulated by enzymatic H2S production and is required for sperm viability.

• MeSH
• cystathionin-gama-lyasa metabolismus   MeSH
• cystein metabolismus   MeSH
• lidé MeSH
• rozmnožování MeSH
• sperma metabolismus   MeSH
• sulfan * metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

There is increasing evidence that bisphenols BPS and BPF, which are analogues of BPA, have deleterious effects on reproduction even at extremely low doses. Indirect exposure via the maternal route (i.e. across the placenta and/or by breastfeeding) is underestimated, although it can be assumed to be a cause of idiopathic female infertility. Therefore, we hypothesised the deleterious effects of exposure to BPA analogues during breastfeeding on the ovarian and oocyte quality of offspring. A 15-day exposure period of pups was designed, whilst nursing dams (N ≥ 6 per experimental group) were treated via drinking water with a low (0.2 ng/g body weight/day) or moderate (20 ng/g body weight/day) dose of bisphenol, mimicking real exposure in humans. Thereafter, female pups were bred to 60 days and oocytes were collected. Immature oocytes were used in the in-vitro maturation assay; alternatively, in-vivo-matured oocytes were isolated and used for parthenogenetic activation. Both in-vitro- and in-vivo-matured oocytes were subjected to immunostaining of spindle microtubules (α-tubulin) and demethylation of histone H3 on the lysine K27 (H3K27me2) residue. Although very low doses of both BPS and BPF did not affect the quality of ovarian histology, spindle formation and epigenetic signs were affected. Notably, in-vitro-matured oocytes were significantly sensitive to both doses of BPS and BPF. Although no significant differences in spindle-chromatin quality were identified in ovulated and in-vivo-matured oocytes, developmental competence was significantly damaged. Taken together, our mouse model provides evidence that bisphenol analogues represent a risk to human reproduction, possibly leading to idiopathic infertility in women.

• MeSH
• aparát dělícího vřeténka účinky léků   metabolismus   patologie   MeSH
• benzhydrylové sloučeniny metabolismus   toxicita   MeSH
• epigeneze genetická MeSH
• fenoly metabolismus   toxicita   MeSH
• fertilita účinky léků   MeSH
• hodnocení rizik MeSH
• IVM techniky MeSH
• kojená zvířata MeSH
• laktace metabolismus   MeSH
• matka - expozice noxám MeSH
• mléko metabolismus   MeSH
• myši inbrední ICR MeSH
• oocyty účinky léků   metabolismus   patologie   MeSH
• ovariální rezerva účinky léků   MeSH
• ovarium účinky léků   metabolismus   patofyziologie   MeSH
• sulfony metabolismus   toxicita   MeSH
• těhotenství MeSH
• vývojová regulace genové exprese MeSH
• ženská infertilita chemicky indukované   metabolismus   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bisphenol S (BPS) is widely used to replace the known endocrine disruptor BPA in various products. We evaluated the effect of acute in vivo BPS exposure on oocyte quality, simulating the oral route of exposure via oral gavage. Eight-week-old ICR female mice (N = 15 per experimental group) were exposed to vehicle or BPS1-BPS4 (0.001, 0.1, 10, and 100 ng BPS x g bw-1 day-1, respectively) for seven days. Oocytes were isolated and matured in vitro. We observed that BPS exposure increased aberrant spindle formation in mature oocytes and induced DNA damage. Moreover, BPS3 significantly increased the chromatin repressive marks 5-methyl cytosine (5meC) and H3K27me2 in immature oocytes. In the BPS2 group, the increase in 5meC occurred during oocyte maturation. Transcriptome analysis revealed differential expression of early embryonic development transcripts in BPS2-exposed oocytes. These findings indicate that the biological effect of BPS is non-monotonic, affecting oocyte quality even at concentrations that are orders of magnitude below those measured in humans.

• MeSH
• embryonální vývoj účinky léků   MeSH
• fenoly toxicita   MeSH
• metylace DNA účinky léků   MeSH
• myši inbrední ICR MeSH
• oocyty účinky léků   metabolismus   MeSH
• poškození DNA MeSH
• stanovení celkové genové exprese MeSH
• sulfony toxicita   MeSH
• těhotenství MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The rate of chromosome segregation errors that emerge during meiosis I in the mammalian female germ line are known to increase with maternal age; however, little is known about the underlying molecular mechanism. The objective of this study was to analyze meiotic progression of mouse oocytes in relation to maternal age. Using the mouse as a model system, we analyzed the timing of nuclear envelope breakdown and the morphology of the nuclear lamina of oocytes obtained from young (2 months old) and aged females (12 months old). Oocytes obtained from older females display a significantly faster progression through meiosis I compared to the ones obtained from younger females. Furthermore, in oocytes from aged females, lamin A/C structures exhibit rapid phosphorylation and dissociation. Additionally, we also found an increased abundance of MPF components and increased translation of factors controlling translational activity in the oocytes of aged females. In conclusion, the elevated MPF activity observed in aged female oocytes affects precocious meiotic processes that can multifactorially contribute to chromosomal errors in meiosis I.

• MeSH
• faktor podporující zrání genetika   metabolismus   MeSH
• fosforylace MeSH
• jaderný obal metabolismus   ultrastruktura   MeSH
• meióza * MeSH
• myši MeSH
• oocyty cytologie   metabolismus   MeSH
• posttranslační úpravy proteinů MeSH
• stárnutí genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Bisphenols belong to the endocrine disruptors, affecting reproduction even in extremely low doses. Bisphenol S (BPS) has become widely used as a substitute for the earlier-used bisphenol A; however, its harmlessness is questionable. The aim of this study was to evaluate the effect of BPS on folliculogenesis and oocyte quality after in vivo exposure to low doses of BPS. Four-week-old ICR females (n = 16 in each experimental group) were exposed to vehicle control (VC), BPS1 (0.001 ng BPS.g/bw/day), BPS2 (0.1 ng.g/bw/day), BPS3 (10 ng.g/bw/day) and BPS4 (100 ng.g/bw/day) for 4 weeks. Ovaries were subjected to stereology and nano liquid chromatography-mass spectrometry (LC/MS). Simultaneously, metaphase II oocytes were obtained after pregnant mare serum gonadotrophin and human chorionic gonadotrophin administration, followed by immunostaining. In particular, mating and two-cell embryo flushing were performed. We observed that BPS decreases the amount of ovarian follicles and BPS2 (0.1 ng.g/bw/day) affects the volume of antral follicles. Accordingly, ovarian proteome is affected after BPS2 treatment. While BPS2 dosing results mainly in cytoskeletal damage in matured oocytes, the effects of BPS3 and BPS4 seem to be due instead to epigenetic alterations in oocytes. Arguably, these changes lead to observed affection of in vivo fertilization rate after BPS3 and BPS4 treatment. BPS significantly affects female reproduction astoundingly in extremely low doses. These findings underline the necessity to assess the risk of ongoing BPS exposure for public health.

• MeSH
• choriogonadotropin farmakologie   MeSH
• endokrinní disruptory aplikace a dávkování   MeSH
• fenoly aplikace a dávkování   MeSH
• fertilizace účinky léků   MeSH
• gonadotropiny koňské farmakologie   MeSH
• imunohistochemie MeSH
• myši inbrední ICR MeSH
• myši MeSH
• oocyty účinky léků   metabolismus   MeSH
• ovariální folikul účinky léků   metabolismus   MeSH
• ovarium účinky léků   metabolismus   MeSH
• proteom účinky léků   MeSH
• rozmnožování účinky léků   MeSH
• sulfony aplikace a dávkování   MeSH
• tandemová hmotnostní spektrometrie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• regretable substitution, politovánihodná náhrada, bisfenol S, bisfenol A,
• MeSH
• benzhydrylové sloučeniny farmakologie   škodlivé účinky   toxicita   MeSH
• endokrinní disruptory * farmakologie   škodlivé účinky   MeSH
• fenoly * farmakologie   škodlivé účinky   toxicita   MeSH
• látky znečišťující životní prostředí škodlivé účinky   MeSH
• lidé MeSH
• rozmnožování * účinky léků   MeSH
• sulfony farmakologie   škodlivé účinky   toxicita   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• znečištění životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

Bisphenol A (BPA), a chemical component of plastics, is a widely distributed environmental pollutant and contaminant of water, air, and food that negatively impacts human health. Concerns regarding BPA have led to the use of BPA-free alternatives, one of which is bisphenol S (BPS). However, the effects of BPS are not well characterized, and its specific effects on reproduction and fertility remain unknown. It is therefore necessary to evaluate any effects of BPS on mammalian oocytes. The present study is the first to demonstrate the markedly negative effects of BPS on pig oocyte maturation in vitro, even at doses lower than those humans are exposed to in the environment. Our results demonstrate (1) an effect of BPS on the course of the meiotic cell cycle; (2) the failure of tubulin fibre formation, which controls proper chromosome movement; (3) changes in the supply of maternal mRNA; (4) changes in the protein amounts and distribution of oestrogen receptors α and β and of aromatase; and (5) disrupted cumulus cell expansion. Thus, these results confirm that BPS is an example of regrettable substitution because this substance exerts similar or even worse negative effects than those of the material it replaced.

• MeSH
• aromatasa genetika   MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• fenoly farmakologie   MeSH
• meióza účinky léků   MeSH
• messenger RNA genetika   MeSH
• oocyty cytologie   účinky léků   metabolismus   MeSH
• prasata MeSH
• receptory pro estrogeny genetika   MeSH
• sulfony farmakologie   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Žijeme v „době plastové“. Obrovské množství plastů vstupuje do životního prostředí a z tohoto materiálu se uvolňuje řada chemikálií s endokrinně disrupčními účinky. Bisfenol A (BPA) je znám jako jeden z takových účinných endokrinních disruptorů uvolňovaných z plastů. Tato látka vykazuje široké spektrum negativních efektů na zdraví zvířat i lidí. Proto bylo používání BPA v řadě lidských oborů omezeno a u mnoha výrobků je garantováno, že BPA neobsahují. BPA může v plastech chybět, jen pokud je nahrazen jinými látkami. Jako náhrada za BPA se často používá bisfenol S (BPS), i když jeho endokrinně disrupční účinky jsou prozkoumány jen velmi málo. Jako chemikálie, jejíž používání podléhá mnohem slabší legislativní regulaci než její předchůdce, je nyní BPS používán v mnoha materiálech. Nově získávané poznatky ale stále jasněji ukazují, že BPS není zdaleka bezpečná látka. Nenápadná náhrada BPA za BPS může být vnímána jako zlepšení. Ale zdá se, že tomu přesně naopak. S tím, jak se BPS šíří naším „do plastu zabaleným“ světem, jsme se jen dostali z bláta do louže.

We are living in the “Age of Plastics”. A vast amount of this material enters the environment, with chemicals released from the bulk of this matter often exhibiting endocrine-disrupting effects. Bisphenol A (BPA), originating from plastics, is well-known as such a potent endocrine disruptor. This compound exhibits wide spectra of detrimental effects on animal and human health. For these reasons, the use of BPA has been limited in many human activities and bisphenol A-free products are now guaranteed. As a key compound of many plastics, BPA could not be omitted from plastics without being replaced by other chemicals. Bisphenol S (BPS) is often chosen as a substitute for BPA, although its endocrine-disruptive effects are poorly known. As a chemical facing much less stringent legislation than BPA, its forerunner, BPS is now widely used in many materials. However, an increasing volume of new knowledge indicates that BPS is far from safe. The “silent” substitution of BPA with BPS could be perceived as an improvement. However, the converse appears to be true. With BPS spreading through our “plastic-encased” world, we are going from bad to worse.

• Klíčová slova
• bisfenol S, antropocén,
• MeSH
• bisfenol A-glycidyl methakrylát toxicita   MeSH
• endokrinní disruptory MeSH
• lidé MeSH
• obezita MeSH
• rozmnožování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH