Systems Biology in Reproductive Medicine最新文献

Sperm antigenicity has been implicated as a regulatory factor for acquiring fertilizing competence in the female reproductive tract. Overt immune response against the sperm proteins leads to idiopathic infertility. Hence, the aim of the study was to evaluate the influence of the auto-antigenic potential of sperm on the antioxidant status, metabolic activities and reactive oxygen species (ROS) in bovine. Semen from Holstein-Friesian bulls (n = 15) was collected and classified into higher (HA, n = 8) and lower (LA, n = 7) antigenic groups based on micro-titer agglutination assay. The neat semen was subjected to the evaluation of bacterial load, leukocyte count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lipid peroxidation (LPO) levels. Antioxidant activities in seminal plasma and intracellular ROS levels in the post-thawed sperm were estimated. The number of leukocytes was lower (p < .05) in the HA than the LA semen. The percentage of metabolically active sperm was higher (p < .05) in HA than the LA group. The activities of total non-enzymatic antioxidant, superoxide dismutase (SOD) and catalase (CAT) were higher (p < .05) while glutathione peroxidase activity was lower (p < .05) in the seminal plasma of LA group. The LPO levels of neat sperm and the percentage sperm positive for intracellular ROS in the cryopreserved sample were lower (p < .05) in the HA group. Auto-antigenic levels were positively correlated with the percentage of metabolically active sperm (r = 0.73, p < .01). However, the seminal auto-antigenicity was negatively (p < .05) correlated with the levels of SOD (r=-0.66), CAT (r=-0.72), LPO (r=-0.602) and intracellular ROS (r=-0.835). The findings were represented in graphical abstract. It is inferred that the higher auto-antigenic levels protect the quality of bovine semen by promoting sperm metabolism and lowering ROS and LPO levels.

Environmental aluminum intoxication has shown increasingly alarming negative consequences on reproductive health. This needs mechanistic exploration and preventive management using medicines like herbal supplementation. The ameliorative effects of naringenin (NAR) against AlCl₃-induced reproductive toxicity were thus evaluated in this study by assessing testicular dysfunction in albino male mice. A group of mice was treated with AlCl₃ (10 mg/kg b.w./day) and then with NAR (10 mg/kg b.w./day) for a total of sixty-two days. Results show that treatment of AlCl₃ significantly reduced the body weight and testis weight of mice. AlCl₃ caused oxidative damage in mice as evidenced by an increase in the concentration of nitric oxide, advanced oxidation of protein product, protein carbonylation, and lipid peroxidation. Furthermore, diminished activity of antioxidant moieties included superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, and oxidized glutathione. Several histological changes, such as spermatogenic cell degeneration, germinal epithelium detachment, and structural abnormalities in seminiferous tubules, were observed in AlCl₃-treated mice. Oral administration of NAR was found to restore body weight and testes weight and ameliorated reproductive dysfunctions. NAR decreased oxidative stress, replenished the antioxidant defense system, and improved histopathological alterations in the AlCl₃-treated testes. Therefore, the present study suggests that the supplementation of NAR may be a beneficial strategy to mitigate AlCl₃-induced reproductive toxicity and testicular dysfunction.

Azoospermia can be diagnosed with spermiogram analysis, and karyotyping is the golden standard to explain the etiology. In this study, we investigated two male cases with azoospermia and male infertility for chromosomal abnormalities. Their phenotypes and physical and hormonal examinations were both normal. In karyotyping G-banding and NOR staining, a rare ring chromosome 21 abnormality was detected in the cases and no microdeletion in chromosome Y. Ring abnormality, deletion size, and deleted regions were shown with subtelomeric FISH (.ish r(21)(p13q22.3?)(D21S1446-)) and array CGH analyses. Due to the findings, bioinformatics, protein, and pathway analyses were done to detect a candidate gene through common genes in two cases' deleted regions or ring chromosome 21.

To clarify the effect of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) combined with trophectoderm (TE) biopsy on the pregnancy outcomes of idiopathic recurrent pregnancy loss (iRPL) and idiopathic recurrent implantation failure (iRIF), we conducted a retrospective cohort study of 212 iRPL couples and 66 iRIF couples who underwent PGT-A or conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. The implantation rate (IR) per transfer (64.2%), clinical pregnancy rate (CPR) per transfer (57.5%), and live birth rate (LBR) per transfer (45%) of iRPL couples of the PGT-A treatment group were significantly higher (p < 0.05) than those of the conventional IVF/ICSI group (IR per transfer,38.2%; CPR per transfer,33.3%; LBR per transfer, 28.4%), whereas the pregnancy loss rate (PLR) per transfer was similar between the two groups. These effects were also significant (p < 0.05) in iRPL couples with advanced maternal age (AMA, ≥35 years), whereas no significant differences were found in clinical outcomes between the PGT-A and conventional IVF/ICSI groups in younger iRPL couples (<35 years). The cumulative clinical outcomes of iRPL couples were comparable between the PGT-A and conventional IVF/ICSI groups. No significant differences were found in any clinical outcomes between the PGT-A and conventional IVF/ICSI groups for young or AMA couples with iRIF. In conclusion, NGS-based PGT-A involving TE biopsy may be useful for iRPL women to shorten the time to pregnancy and reduce their physical and psychological burden, especially for iRPL women with AMA; however, couples with iRIF may not benefit from PGT-A treatment. Considering the small sample size of the iRIF group, further investigations with a larger sample size are needed to verify our findings.

Oligoasthenozoospermia is becoming a serious problem, but effective prevention or treatment is lacking. Hyperoside, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. In this study, we used cyclophosphamide (CTX: 50 mg/kg) to establish a mouse model of Oligoasthenozoospermia to investigate the therapeutic effect of hyperoside (30 mg/kg) on CTX-induced oligoasthenozoospermia. All mice were divided into four groups: blank control group (Control), treatment control group (Hyp), disease group (CTX) and treatment group (CTX + H). Mice body weight, testicular weight, sperm parameters and testicular histology were used to assess the reproductive capacity of mice and to explore the underlying mechanism of hyperoside in the treatment of oligoasthenozoospermia by assessing hormone levels, protein levels of molecules related to hormone synthesis and transcript levels of important genes related to spermatogenesis. Treatment with hyperoside significantly improved sperm density, sperm viability and testicular function compared to untreated oligoasthenozoospermia mice. In mechanism, treatment with hyperoside resulted in significant improvement in pathological changes in spermatogenic tubules, with an increase in testosterone production, and upregulations of Protein Kinase CAMP-Activated Catalytic Subunit Beta (PRKACB), Steroidogenic Acute Regulatory Protein (STAR), and Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) for testosterone production. Hyperoside also promoted the cell cycle of germ cells and up-regulated meiosis and spermatogenesis-related genes, including DNA Meiotic Recombinase 1 (Dmc1), Ataxia telangiectasia mutated (Atm) and RAD21 Cohesin Complex Component (Rad21). In conclusion, hyperoside exerted protective effects on oligoasthenozoospermia mice by regulating testosterone production, meiosis and sperm maturation of germ cells.

The differential expression and direct targeting of mRNA by miRNA are two main logics of the traditional approach to constructing the miRNA-mRNA network. This approach, could be led to the loss of considerable information and some challenges of direct targeting. To avoid these problems, we analyzed the rewiring network and constructed two miRNA-mRNA expression bipartite networks for both normal and primary prostate cancer tissue obtained from PRAD-TCGA. We then calculated beta-coefficient of the regression-model when miR was dependent and mRNA independent for each miR and mRNA and separately in both networks. We defined the rewired edges as a significant change in the regression coefficient between normal and cancer states. The rewired nodes through multinomial distribution were defined and network from rewired edges and nodes was analyzed and enriched. Of the 306 rewired edges, 112(37%) were new, 123(40%) were lost, 44(14%) were strengthened, and 27(9%) weakened connections were discovered. The highest centrality of 106 rewired mRNAs belonged to PGM5, BOD1L1, C1S, SEPG, TMEFF2, and CSNK2A1. The highest centrality of 68 rewired miRs belonged to miR-181d, miR-4677, miR-4662a, miR-9.3, and miR-1301. SMAD and beta-catenin binding were enriched as molecular functions. The regulation was a frequently repeated concept in the biological process. Our rewiring analysis highlighted the impact of β-catenin and SMAD signaling as also some transcript factors like TGFB1I1 in prostate cancer progression. Altogether, we developed a miRNA-mRNA co-expression bipartite network to identify the hidden aspects of the prostate cancer mechanism, which traditional analysis -like differential expression- was not detect it.

Infertility is clinically defined as the inability to achieve pregnancy within 12 months of regular unprotected sexual intercourse and affects 15% of couples worldwide. Therefore, the identification of novel biomarkers that can accurately predict male reproductive health and couples' reproductive success is of major public health significance. The objective of this pilot study is to test whether untargeted metabolomics is capable of discriminating reproductive outcomes and understand associations between the internal exposome of seminal plasma and the reproductive outcomes of semen quality and live birth among ten participants undergoing assisted reproductive technology (ART) in Springfield, MA. We hypothesize that seminal plasma offers a novel biological matrix by which untargeted metabolomics is able to discern male reproductive status and predict reproductive success. The internal exposome data was acquired using UHPLC-HR-MS on randomized seminal plasma samples at UNC at Chapel Hill. Unsupervised and supervised multivariate analyses were used to visualize the differentiation of phenotypic groups classified by men with normal or low semen quality based on World Health Organization guidelines as well as by successful ART: live birth or no live birth. Over 100 exogenous metabolites, including environmentally relevant metabolites, ingested food components, drugs and medications, and metabolites relevant to microbiome-xenobiotic interaction, were identified and annotated from the seminal plasma samples, through matching against the NC HHEAR hub in-house experimental standard library. Pathway enrichment analysis indicated that fatty acid biosynthesis and metabolism, vitamin A metabolism, and histidine metabolism were associated sperm quality; while pathways involving vitamin A metabolism, C21-steroid hormone biosynthesis and metabolism, arachidonic acid metabolism, and Omega-3 fatty acid metabolism distinguished live birth groups. Taken together, these pilot results suggest that seminal plasma is a novel matrix to study the influence of the internal exposome on reproductive health outcomes. Future research aims to increase the sample size to validate these findings.

There is a correlation between teratozoospermia and production of reactive oxygen species leading to poor assisted reproductive techniques outcomes. This study aimed to examine the effect of plasma-rich in growth factors (PRGF) on teratozoospermic samples. Twenty-five teratozoospermic samples were included in this study. After sperm preparation, it was divided into four groups, including 0 (control), 1, 5, and 10% PRGF. Sperm motility, viability (eosin-nigrosin staining), morphology (Papanicolaou staining), DNA fragmentation (sperm chromatin dispersion test), mitochondrial membrane potential (JC-1 staining by flow cytometry), and lipid peroxidation (measurement of malondialdehyde, MDA) were evaluated before and after 1 h of incubation with or without PRGF. Our results showed that after 1 h of incubation, the addition of 1% PRGF improved sperm progressive motility (47.72 ± 13.76%) compared to the control group (17.36 ± 8.50%) (p < 0.001). Also, 1% PRGF preserved the sperm's total motility (77.50 ± 13.28% vs. 65.63 ± 19.03%, for 1% PRGF and control, respectively) and viability after incubation. The rate of normal sperm morphology was the same between different groups. Higher mitochondrial membrane potential and lower DNA fragmentation were also observed in sperm treated with different concentrations of PRGF compared to the control group, but the differences were non-significant. The MDA levels were significantly decreased in PRGF-treated groups compared to the control group (0.99 ± 0.62, 0.95 ± 0.33, 0.95 ± 0.79, and 1.49 ± 0.27 for 1% PRGF, 5% PRGF, 10% PRGF and control, respectively). Based on our results, it seems that PRGF incubation can improve sperm parameters and especially decrease the level of malondialdehyde as an indicator of oxidative stress, which is one of the main problems of teratozoospermic samples.