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1.
Sci Rep ; 12(1): 11426, 2022 07 06.
Article in English | MEDLINE | ID: mdl-35794129

ABSTRACT

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 ß-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.


Subject(s)
Hydrogen Sulfide , Cystathionine gamma-Lyase/metabolism , Cysteine/metabolism , Humans , Hydrogen Sulfide/metabolism , Male , Reproduction , Semen/metabolism
2.
Toxicol Appl Pharmacol ; 413: 115409, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33476676

ABSTRACT

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.


Subject(s)
Benzhydryl Compounds/toxicity , Fertility/drug effects , Infertility, Female/chemically induced , Lactation/metabolism , Milk/metabolism , Oocytes/drug effects , Ovary/drug effects , Phenols/toxicity , Sulfones/toxicity , Animals , Animals, Suckling , Benzhydryl Compounds/metabolism , Epigenesis, Genetic , Female , Gene Expression Regulation, Developmental , In Vitro Oocyte Maturation Techniques , Infertility, Female/metabolism , Infertility, Female/pathology , Infertility, Female/physiopathology , Maternal Exposure , Mice, Inbred ICR , Oocytes/metabolism , Oocytes/pathology , Ovarian Reserve/drug effects , Ovary/metabolism , Ovary/physiopathology , Phenols/metabolism , Pregnancy , Risk Assessment , Spindle Apparatus/drug effects , Spindle Apparatus/metabolism , Spindle Apparatus/pathology , Sulfones/metabolism
3.
Mol Reprod Dev ; 85(10): 760-767, 2018 10.
Article in English | MEDLINE | ID: mdl-30098056

ABSTRACT

Genetic abnormalities have been considered a significant cause of male infertility. Increased expression of SPATA33 during the first wave of spermatogenesis indicates its possible association with the meiotic process. The aim of the current study was to investigate the genetic variations in the SPATA33 gene and its expression in patients with nonobstructive azoospermia (NOA). A total of 100 Iranian NOA men with idiopathic infertility were taken as the case group. The control group comprised 100 fertile men who had at least one child. The presence of nucleotide variations was analyzed in both groups using the standard polymerase chain reaction (PCR) sequencing technique. For mRNA and protein expression studies, testicular biopsy specimens from 27 patients were subdivided into three groups: nine obstructive azoospermic patients with hypospermatogenesis as control; nine maturation arrest (MA) and nine Sertoli cell-only syndromes (SCOS) as case groups. The expression of SPATA33 at both mRNA and protein levels was compared among these three groups using the reverse transcription PCR technique, the realtime-PCR technique, and immunohistochemistry. Mutation analysis of the SPATA33 gene revealed five nucleotide changes among the population studied. All but one showed no significant differences between the groups. The genotype distributions of rs112536073A > T in the transcription factor binding site region with heterozygote and homozygote genotypes were significantly different ( p < 0.05) between the two groups. More heterozygotes of this polymorphism were observed in patients, whereas more homozygotes were detected in controls. Accordingly, the current study illustrated that alterations in SPATA33 gene, at least those found in this study, may not impair spermatogenesis in patients with NOA. Reduction of gene expression at the level of mRNA in patients with SCOS can be interpreted by the absence of germ cells in the testicular tissue of these patients.


Subject(s)
Azoospermia/metabolism , Gene Expression Regulation , Oligospermia/metabolism , Testis/metabolism , Adult , Aged , Azoospermia/genetics , Azoospermia/pathology , Biopsy , Humans , Iran , Male , Middle Aged , Oligospermia/genetics , Oligospermia/pathology , Real-Time Polymerase Chain Reaction , Response Elements , Testis/pathology
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