Hydrogen sulfide (H2S) is a gaseous signaling molecule produced in the body by three enzymes: cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S is crucial in various physiological processes associated with female mammalian reproduction. These include estrus cycle, oocyte maturation, oocyte aging, ovulation, embryo transport and early embryo development, the development of the placenta and fetal membranes, pregnancy, and the initiation of labor. Despite the confirmed presence of H2S-producing enzymes in all female reproductive tissues, as described in this review, the exact mechanisms of H2S action in these tissues remain in most cases unclear. Therefore, this review aims to summarize the knowledge about the presence and effects of H2S in these tissues and outline possible signaling pathways that mediate these effects. Understanding these pathways may lead to the development of new therapeutic strategies in the field of women's health and perinatal medicine.

• Keywords
• cystathionine beta synthase, cystathionine gamma lyase, early embryo development, female reproduction, gravidity, hydrogen sulfide, oocyte physiology, uterus,
• Publication type
• Journal Article MeSH
• Review MeSH

Oxidative stress impairs the correct course of meiotic maturation, and it is known that the oocytes are exposed to increased oxidative stress during meiotic maturation in in vitro conditions. Thus, reduction of oxidative stress can lead to improved quality of cultured oocytes. The gasotransmitter carbon monoxide (CO) has a cytoprotective effect in somatic cells. The CO is produced in cells by the enzyme heme oxygenase (HO) and the heme oxygenase/carbon monoxide (HO/CO) pathway has been shown to have an antioxidant effect in somatic cells. It has not yet been investigated whether the CO has an antioxidant effect in oocytes as well. We assessed the level of expression of HO mRNA, using reverse transcription polymerase chain reaction. The HO protein localization was evaluated by the immunocytochemical method. The influence of CO or HO inhibition on meiotic maturation was evaluated in oocytes cultured in a culture medium containing CO donor (CORM-2 or CORM-A1) or HO inhibitor Zn-protoporphyrin IX (Zn-PP IX). Detection of reactive oxygen species (ROS) was performed using the oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate. We demonstrated the expression of mRNA and proteins of both HO isoforms in porcine oocytes during meiotic maturation. The inhibition of HO enzymes by Zn-PP IX did not affect meiotic maturation. CO delivered by CORM-2 or CORM-A1 donors led to a reduction in the level of ROS in the oocytes during meiotic maturation. However, exogenously delivered CO also inhibited meiotic maturation, especially at higher concentrations. In summary, the CO signaling molecule has antioxidant properties in porcine oocytes and may also be involved in the regulation of meiotic maturation.

• Keywords
• Carbon monoxide, Heme oxygenase, Meiotic maturation, Oocyte, Oxidative stress,
• Publication type
• Journal Article MeSH

The role of hydrogen sulfide (H2S) is addressed in Xenopuslaevis oocytes. Three enzymes involved in H2S metabolism, cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase, were detected in prophase I and metaphase II-arrested oocytes and drove an acceleration of oocyte meiosis resumption when inhibited. Moreover, meiosis resumption is associated with a significant decrease in endogenous H2S. On another hand, a dose-dependent inhibition was obtained using the H2S donor, NaHS (1 and 5 mM). NaHS impaired translation. NaHS did not induce the dissociation of the components of the M-phase promoting factor (MPF), cyclin B and Cdk1, nor directly impacted the MPF activity. However, the M-phase entry induced by microinjection of metaphase II MPF-containing cytoplasm was diminished, suggesting upstream components of the MPF auto-amplification loop were sensitive to H2S. Superoxide dismutase and catalase hindered the effects of NaHS, and this sensitivity was partially dependent on the production of reactive oxygen species (ROS). In contrast to other species, no apoptosis was promoted. These results suggest a contribution of H2S signaling in the timing of amphibian oocytes meiosis resumption.

• Keywords
• Xenopus laevis, cell cycle, hydrogen sulfide, meiosis, oocyte,
• MeSH
• Apoptosis drug effects   MeSH
• Cyclin B metabolism   MeSH
• Cystathionine beta-Synthase antagonists & inhibitors   metabolism   MeSH
• Cystathionine gamma-Lyase antagonists & inhibitors   metabolism   MeSH
• Cytoplasm metabolism   MeSH
• Maturation-Promoting Factor metabolism   MeSH
• cdc25 Phosphatases metabolism   MeSH
• Catalase metabolism   MeSH
• Meiosis drug effects   MeSH
• Metaphase drug effects   MeSH
• Oocytes chemistry   enzymology   metabolism   MeSH
• Meiotic Prophase I drug effects   MeSH
• Protein Kinases metabolism   MeSH
• Cell Cycle Proteins metabolism   MeSH
• Xenopus Proteins metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Hydrogen Sulfide metabolism   MeSH
• Sulfides metabolism   pharmacology   MeSH
• Sulfurtransferases antagonists & inhibitors   metabolism   MeSH
• Superoxide Dismutase metabolism   MeSH
• Cell Survival drug effects   MeSH
• Xenopus laevis MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 3-mercaptopyruvate sulphurtransferase MeSH Browser
• CDC25C protein, human MeSH Browser
• CDK1 protein, Xenopus MeSH Browser
• Cyclin B MeSH
• Cystathionine beta-Synthase MeSH
• Cystathionine gamma-Lyase MeSH
• Maturation-Promoting Factor MeSH
• cdc25 Phosphatases MeSH
• Catalase MeSH
• Protein Kinases MeSH
• Cell Cycle Proteins MeSH
• Xenopus Proteins MeSH
• Reactive Oxygen Species MeSH
• sodium bisulfide MeSH Browser
• Hydrogen Sulfide MeSH
• Sulfides MeSH
• Sulfurtransferases MeSH
• Superoxide Dismutase MeSH

BACKGROUND: Hydrogen sulfide has been shown to improve the quality of oocytes destined for in vitro fertilization. Although hydrogen sulfide is capable of modulating ion channel activity in somatic cells, the role of hydrogen sulfide in gametes and embryos remains unknown. Our observations confirmed the hypothesis that the KATP and L-type Ca2+ ion channels play roles in porcine oocyte ageing and revealed a plausible contribution of hydrogen sulfide to the modulation of ion channel activity. RESULTS: We confirmed the benefits of the activation and suppression of the KATP and L-type Ca2+ ion channels, respectively, for the preservation of oocyte quality. CONCLUSIONS: Our experiments identified hydrogen sulfide as promoting the desired ion channel activity, with the capacity to protect porcine oocytes against cell death. Further experiments are needed to determine the exact mechanism of hydrogen sulfide in gametes and embryos.

• Keywords
• Gasotransmitter, Hydrogen sulfide, Ion channel, Oocyte, Oocyte ageing,
• MeSH
• Adenosine Triphosphate MeSH
• Calcium Channel Blockers pharmacology   MeSH
• Potassium Channels, Calcium-Activated drug effects   physiology   MeSH
• Phenotype MeSH
• Minoxidil pharmacology   MeSH
• Oocytes drug effects   metabolism   MeSH
• Swine MeSH
• Signal Transduction drug effects   MeSH
• Cellular Senescence physiology   MeSH
• Hydrogen Sulfide pharmacology   MeSH
• Calcium Channels drug effects   physiology   MeSH
• Verapamil pharmacology   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adenosine Triphosphate MeSH
• Calcium Channel Blockers MeSH
• Potassium Channels, Calcium-Activated MeSH
• Minoxidil MeSH
• Hydrogen Sulfide MeSH
• Calcium Channels MeSH
• Verapamil MeSH

BACKGROUND: The 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. RESULTS: Our 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. CONCLUSIONS: We 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.

• Keywords
• Embryonic development, Epigenetics, H3K9 methylation, SIRT1, Sirtuin,
• Publication type
• Journal Article 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
• Aromatase genetics   MeSH
• Cell Differentiation drug effects   genetics   MeSH
• Phenols pharmacology   MeSH
• Meiosis drug effects   MeSH
• RNA, Messenger genetics   MeSH
• Oocytes cytology   drug effects   metabolism   MeSH
• Swine MeSH
• Receptors, Estrogen genetics   MeSH
• Sulfones pharmacology   MeSH
• Gene Expression Regulation, Developmental drug effects   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aromatase MeSH
• bisphenol S MeSH Browser
• Phenols MeSH
• RNA, Messenger MeSH
• Receptors, Estrogen MeSH
• Sulfones MeSH

Creation of both gametes, sperm and oocyte, and their fusion during fertilization are essential step for beginning of life. Although molecular mechanisms regulating gametogenesis, fertilization, and early embryonic development are still subjected to intensive study, a lot of phenomena remain unclear. Based on our best knowledge and own results, we consider gasotransmitters to be essential for various signalisation in oocytes and embryos. In accordance with nitric oxide (NO) and hydrogen sulfide (H2S) physiological necessity, their involvement during oocyte maturation and regulative role in fertilization followed by embryonic development have been described. During these processes, NO- and H2S-derived posttranslational modifications represent the main mode of their regulative effect. While NO represent the most understood gasotransmitter and H2S is still intensively studied gasotransmitter, appreciation of carbon monoxide (CO) role in reproduction is still missing. Overall understanding of gasotransmitters including their interaction is promising for reproductive medicine and assisted reproductive technologies (ART), because these approaches contend with failure of in vitro assisted reproduction.

• MeSH
• Reproductive Techniques, Assisted * MeSH
• Gametogenesis physiology   MeSH
• Gasotransmitters metabolism   physiology   MeSH
• Humans MeSH
• Oocytes metabolism   physiology   MeSH
• Nitric Oxide metabolism   physiology   MeSH
• Carbon Monoxide metabolism   physiology   MeSH
• Protein Processing, Post-Translational MeSH
• Hydrogen Sulfide metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Gasotransmitters MeSH
• Nitric Oxide MeSH
• Carbon Monoxide MeSH
• Hydrogen Sulfide MeSH