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.

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 exposure to low doses of BPS. Four-week-old ICR females ( = 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 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.

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BackgroundThe histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD+-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development.ResultsOur results show that SIRT1 activators resveratrol and BML-278 increased H3K9 methylation and suppressed H3K9 acetylation in both the paternal and maternal pronucleus. Inversely, SIRT1 inhibitors nicotinamide and sirtinol suppressed methylation and increased acetylation of pronuclear H3K9. Evaluation of early embryonic development confirmed positive effect of selective SIRT1 activation on blastocyst formation rate (5.2 ± 2.9% versus 32.9 ± 8.1% in vehicle control and BML-278 group, respectively; P ≤ 0.05). Stimulation of SIRT1 activity coincided with fluorometric signal intensity of ooplasmic ubiquitin ligase MDM2, a known substrate of SIRT1 and known limiting factor of epigenome remodeling.ConclusionsWe conclude that SIRT1 modulates zygotic histone code, obviously through direct deacetylation and via non-histone targets resulting in increased H3K9me3. These changes in zygotes lead to more successful pre-implantation embryonic development and, indeed, the specific SIRT1 activation due to BML-278 is beneficial for in vitro embryo production and blastocyst achievement.Electronic supplementary materialThe online version of this article (10.1186/s40104-017-0214-0) contains supplementary material, which is available to authorized users.

A range of substances that are released into the environment, foodstuffs and drinking water as a result of human activity were originally considered relatively harmless, and it was only later that their adverse effects were discovered. In general the use of such substances is currently restricted, and they are often replaced by other substances. This applies also in the case of a range of endocrine disruptors. These substances have the capacity to disturb the balance of physiological functions of the organism on the level of hormonal regulation, and their pleiotropic spectrum of effects is very difficult to predict. Endocrine disruptors include the currently intensively studied bisphenol A (BPA), a prevalent environmental pollutant and contaminant of both water and foodstuffs. BPA has a significantly negative impact on human health, particularly on the regulation mechanisms of reproduction, and influences fertility. The ever increasingly stringent restriction of the industrial production of BPA is leading to its replacement with analogues, primarily with bisphenol S (BPS), which is not subject to these restrictions and whose impacts on the regulation of reproduction have not yet been exhaustively studied. However, the limited number of studies at disposal indicates that BPS may be at least as harmful as BPA. There is therefore a potential danger that the replacement of BPA with BPS will become one of the cases of regrettable substitution, in which the newly used substances manifest similar or even worse negative effects than the substances which they have replaced. The objective of this review is to draw attention to ill-advised replacements of endocrine disruptors with substances whose effects are not yet tested, and which may represent the same risks for the environment, for the reproduction of males and females, and for human health as have been demonstrated in the case of the originally used substances.

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