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.

Chromatin remodeling, including histone post-translational modifications, during spermatogenesis can affect sperm quality and fertility, and epigenetic marks may therefore be useful for clinical evaluations of sperm. Together with histone hyperacetylation, the dimethylation of histone H3 on lysine K4 (H3K4me2) is also required during protamination. Accordingly, we evaluated the utilization of this epigenetic mark for the identification of sperm with decrease quality and immature chromatin. In this study, 99 semen samples, including 22 normozoospermic (N), 63 asthenozoospermic (A), and 14 oligoasthenozoospermic (OA) samples, were comprehensively analyzed with respect to H3K4me2 levels, DNA damage (DNA fragmentation index, DFI), and sperm immaturity (high DNA stainability, %HDS), as determined by a sperm chromatin structure assay using flow cytometry. We detected a significant relationship between H3K4me2 and %HDS (r = 0.47; p < 0.001). Furthermore, we observed negative correlations between H3K4me2 and sperm concentration, motility, and mitochondrial activity (p < 0.05). The increase in immaturity as semen quality decreased (N > A > OA) indicates the importance of chromatin immaturity and histone code deviations in sperm evaluations. Using various approaches, our study elucidated H3K4me2 as a molecular marker of sperm quality with potential use in reproductive medicine.

Background Despite a multifactorial approach being taken for the evaluation of bull semen quality in many animal breeding centres worldwide, reliable prediction of bull fertility is still a challenge. Recently, attention has turned to molecular mechanisms, which could uncover potential biomarkers of fertility. One of these mechanisms is DNA methylation, which together with other epigenetic mechanisms is essential for the fertilising sperm to drive normal embryo development and establish a viable pregnancy. In this study, we hypothesised that bull sperm DNA methylation patterns are related to bull fertility. We therefore investigated DNA methylation patterns from bulls used in artificial insemination with contrasting fertility scores. Results The DNA methylation patterns were obtained by reduced representative bisulphite sequencing from 10 high-fertility bulls and 10 low-fertility bulls, having average fertility scores of − 6.6 and + 6.5%, respectively (mean of the population was zero). Hierarchical clustering analysis did not distinguish bulls based on fertility but did highlight individual differences. Despite this, using stringent criteria (DNA methylation difference ≥ 35% and a q-value < 0.001), we identified 661 differently methylated cytosines (DMCs). DMCs were preferentially located in intergenic regions, introns, gene downstream regions, repetitive elements, open sea, shores and shelves of CpG islands. We also identified 10 differently methylated regions, covered by 7 unique genes (SFRP1, STXBP4, BCR, PSMG4, ARSG, ATP11A, RXRA), which are involved in spermatogenesis and early embryonic development. Conclusion This study demonstrated that at specific CpG sites, sperm DNA methylation status is related to bull fertility, and identified seven differently methylated genes in sperm of subfertile bulls that may lead to altered gene expression and potentially influence embryo development.

Since sperm size and form do not necessarily provide information on internal sperm structures, novel sperm markers need to be found in order to conduct assisted reproductive therapies (ART) successfully. Currently, the priority of andrologists is not only to select those sperm able to fertilize the oocyte, but also a high quality of sperm that will guarantee a healthy embryo. Evidence of this shows us the importance of studying sperm intensively on genetic and epigenetic levels, because these could probably be the cause of a percentage of infertility diagnosed as idiopathic. Thus, more attention is being paid to posttranslational modifications as the key for better understanding of the fertilization process and its impact on embryo and offspring. Advances in the discovery of new sperm markers should go hand in hand with finding appropriate techniques for selecting the healthiest sperm, guaranteeing its non-invasiveness. To date, most sperm selection techniques can be harmful to sperm due to centrifugation or staining procedures. Some methods, such as microfluidic techniques, sperm nanopurifications, and Raman spectroscopy, have the potential to make selection gentle to sperm, tracking small abnormalities undetected by methods currently used. The fact that live cells could be analyzed without harmful effects creates the expectation of using them routinely in ART. In this review, we focus on the combination of sperm epigenetic status (modifications) as quality markers, with non-invasive sperm selection methods as novel approaches to improve ART outcomes.

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The objective of this work was to elucidate whether a sperm selection method that combines rheotaxis and microfluidics can improve the selection of spermatozoa over density gradient and swim-up. For this purpose human sperm selected by rheotaxis were compared against density gradient, swim-up and a control group of non-selected spermatozoa in split frozen-thawed (FT) and fresh (F) semen samples. Sperm quality was assessed in terms of motility, morphology, DNA fragmentation index (DFI), viability, acrosome integrity and membrane fluidity. Using a mouse model, we compared fertilisation and embryo development rates after performing ICSI with spermatozoa, sorted using rheotaxis or swim-up. Selection by rheotaxis yielded a sperm population with reduced DFI than the control (P < 0.05), improved normal morphology (P < 0.001) and higher total motility (TM; P < 0.001) than the other techniques studied in F and FT samples. Swim-up increased TM compared to density gradient and control in FT or F samples (P < 0.001), and yielded lower DFI than the control with F samples (P < 0.05). In FT samples, selection by rheotaxis yielded sperm with higher viability than control, density gradient and swim-up (P < 0.01) while acrosomal integrity and membrane fluidity were maintained. When mouse spermatozoa were selected for ICSI using rheotaxis compared to swim-up, there was an increase in fertilisation (P < 0.01), implantation (P < 0.001) and foetal development rates (P < 0.05). These results suggest that, in the absence of non-destructive DNA testing, the positive rheotaxis can be used to select a population of low DNA fragmentation spermatozoa with high motility, morphology and viability, leading to improved embryo developmental rates.

Background SIRT1 histone deacetylase acts on many epigenetic and non-epigenetic targets. It is thought that SIRT1 is involved in oocyte maturation; therefore, the importance of the ooplasmic SIRT1 pool for the further fate of mature oocytes has been strongly suggested. We hypothesised that SIRT1 plays the role of a signalling molecule in mature oocytes through selected epigenetic and non-epigenetic regulation. Results We observed SIRT1 re-localisation in mature oocytes and its association with spindle microtubules. In mature oocytes, SIRT1 distribution shows a spindle-like pattern, and spindle-specific SIRT1 action decreases α-tubulin acetylation. Based on the observation of the histone code in immature and mature oocytes, we suggest that SIRT1 is mostly predestined for an epigenetic mode of action in the germinal vesicles (GVs) of immature oocytes. Accordingly, BML-278-driven trimethylation of lysine K9 in histone H3 in mature oocytes is considered to be a result of GV epigenetic transformation. Conclusions Taken together, our observations point out the dual spatiotemporal SIRT1 action in oocytes, which can be readily switched from the epigenetic to non-epigenetic mode of action depending on the progress of meiosis. Electronic supplementary material The online version of this article (10.1186/s40104-019-0372-3) contains supplementary material, which is available to authorized users.

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.