AB215. Variants in the SRD5A2 gene are associated with quality of semen
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ABSTRACT:
SUBMITTER: Zhao D
PROVIDER: S-EPMC4708336 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
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Project description:The 5-alpha-reductase type 2 deficiency (5ARD2) is an autosomal recessive condition associated with impairment in the conversion of testosterone to dihydrotestosterone. This condition leads to undervirilisation in 46,XY individuals. To date, there have been more than 100 variations identified in the gene responsible for 5ARD2 development (steroid 5-alpha-reductase 2, SRD5A2). However, few studies have examined the molecular characterisation of Indonesian 5ARD2 cases. In the current study, we analysed 37 subjects diagnosed with 46,XY DSD (disorders of sex development) with confirmed variations in the SRD5A2 gene. We examined results from testosterone/dihydrotestosterone (T/DHT) and urinary etiocholanolone/androsterone (Et/An) ratios, as well as from molecular and clinical analyses. Twelve variants in the SRD5A2 gene were identified, and 6 of which were novel, namely, c.34-38delGinsCCAGC, p.Arg50His, p.Tyr136 ? , p.Gly191Arg, p.Phe194Ile, and p.Ile253Val variants. Moreover, we determined that 20 individuals contained harmful mutations, while the remaining 17 variants were benign. Those containing harmful mutations exhibited more severe phenotypes with median external genitalia masculinisation scores (EMS) of 3 (1.5-9) and were more likely to be diagnosed at a later age, reared as female, and virilised at pubertal age. In addition, the respective sensitivities for detecting severe 5ARD2 cases using T/DHT (cutoff: 10) and urinary Et/An ratios (cutoff: 0.95) were 85% and 90%, whereas mild cases were only identified with 64.7% and 47.1% sensitivity, respectively. Although we were unable to identify clear correlations between genotypic and phenotypic characteristics in this study, we clearly showed that individuals who were homozygous or compound heterozygous for any of the harmful mutations were more likely to exhibit classic 5ARD2 phenotypes, lower EMS, female assignment at birth, and virilisation during puberty. These results serve to inform the development of improved clinical and molecular 5ARD2 diagnostic approaches, specifically in Indonesian patients.
| S-EPMC6914983 | biostudies-literature
Project description:Background: The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the SRD5A2 gene, which encodes this enzyme, are responsible for 46,XY DSD. Objective: The objective of the study was to investigate the genetic etiology of 46,XY DSD in two Mexican families with affected children. Materials and methods: The SRD5A2 gene of the parents and affected children was screened in both families via polymerase chain reaction amplification and DNA direct sequencing. The role of genetic variants in enzymatic activity was tested by site-directed mutagenesis. Results: Subject 1 presented two variants: p.Glu197Asp and p.Pro212Arg. Subject 2 was homozygous for the variant p.Glu197Asp. The two variants were reported in early studies. The directed mutagenesis study showed that the p.Glu197Asp and p.Pro212Arg variants lead to a total loss of enzymatic activity and, consequently, abnormal genitalia development in the patients. Conclusion: These results suggest that p.Glu197Asp and p.Pro212Arg are pathogenic variants that lead to the phenotypic expression of DSD. 5α-RD2 is of extreme importance not only because of its frequency (it is rare) but also because of its significance in understanding the mechanism of androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior.
| S-EPMC8829113 | biostudies-literature
Project description:PurposeCell-free mRNAs (cfmRNAs) were quantitatively measured in human seminal plasma and its relationship with semen quality was investigated.MethodsHerein, a prospectively, controlled investigation was performed to study seminal plasma HSPA2 and uPA cfmRNA alterations between 21 asthenozoospermic patients and 16 normozoospermic individuals. Standard semen analysis was performed and seminal plasma cfmRNAs content was measured by real-time quantitative PCR. In addition, the regression analysis between seminal plasma cfmRNAs expression and semen parameters was performed.ResultsSeminal plasma HSPA2, but not uPA cfmRNA indicated significant difference between normozoospermia and asthenozoospermia men (P?=?0.02444 and 0.07811, respectively). Negative correlation between HSPA2 cfmRNA and sperm motility (R (2)?=?0.213, P?=?0.004) as well as sperm concentration (R (2)?=?0.133, P?=?0.026) were revealed. However, no correlation was found between seminal plasma uPA cfmRNA content and semen parameters.ConclusionsOur data suggest that seminal plasma HSPA2 cfmRNA is different between asthenozoospermic and normozoospermic individuals and it might be an indicator for semen quality.
| S-EPMC4974226 | biostudies-literature
Project description:BackgroundTo examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection.MethodsA total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.ResultsTwo SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis.ConclusionsThis study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.
| S-EPMC10546680 | biostudies-literature
Project description:Genetic markers have been used to assess the freezability of semen. With the advancement in molecular genetic techniques, it is possible to assess the relationships between sperm functions and gene polymorphisms. In this study, variant calling analysis of RNA-Seq datasets was used to identify single nucleotide polymorphisms (SNPs) in boar spermatozoa and to explore the associations between SNPs and post-thaw semen quality. Assessment of post-thaw sperm quality characteristics showed that 21 boars were considered as having good semen freezability (GSF), while 19 boars were classified as having poor semen freezability (PSF). Variant calling demonstrated that most of the polymorphisms (67%) detected in boar spermatozoa were at the 3'-untranslated regions (3'-UTRs). Analysis of SNP abundance in various functional gene categories showed that gene ontology (GO) terms were related to response to stress, motility, metabolism, reproduction, and embryo development. Genomic DNA was isolated from sperm samples of 40 boars. Forty SNPs were selected and genotyped, and several SNPs were significantly associated with motility and membrane integrity of frozen-thawed (FT) spermatozoa. Polymorphism in SCLT1 gene was associated with significantly higher motility and plasma membrane integrity of FT spermatozoa from boars of the GSF group compared with those of the PSF group. Likewise, polymorphisms in MAP3K20, MS4A2, and ROBO1 genes were significantly associated with reduced cryo-induced lipid peroxidation and DNA damage of FT spermatozoa from boars of the GSF group. Candidate genes with significant SNP associations, including APPL1, PLBD1, FBXO16, EML5, RAB3C, OXSR1, PRICKLE1, and MAP3K20 genes, represent potential markers for post-thaw semen quality, and they might be relevant for future improvement in the selection procedure of boars for cryopreservation. The findings of this study provide evidence indicating that polymorphisms in genes expressed in spermatozoa could be considered as factors associated with post-thaw semen quality.
| S-EPMC7084667 | biostudies-literature
Project description:There is increasing evidence from non-human animals that males adjust their ejaculate expenditure according to the risk of sperm competition. In this study we show that, after controlling for lifestyle factors known to influence semen quality, human males viewing images depicting sperm competition had a higher percentage of motile sperm in their ejaculates. Many lifestyle variables were confirmed to influence semen quality, including the recent suggestion that storage of mobile phones close to the testes can decrease semen quality.
| S-EPMC1617155 | biostudies-literature
Project description:BackgroundAmbient air pollution is associated with systemic increases in oxidative stress, to which sperm are particularly sensitive. Although decrements in semen quality represent a key mechanism for impaired fecundability, prior research has not established a clear association between air pollution and semen quality. To address this, we evaluated the association between ambient air pollution and semen quality among men with moderate air pollution exposure.MethodsOf 501 couples in the LIFE study, 467 male partners provided one or more semen samples. Average residential exposure to criteria air pollutants and fine particle constituents in the 72 days before ejaculation was estimated using modified Community Multiscale Air Quality models. Generalized estimating equation models estimated the association between air pollutants and semen quality parameters (volume, count, percent hypo-osmotic swollen, motility, sperm head, morphology and sperm chromatin parameters). Models adjusted for age, body mass index, smoking and season.ResultsMost associations between air pollutants and semen parameters were small. However, associations were observed for an interquartile increase in fine particulates ≤2.5 µm and decreased sperm head size, including -0.22 (95% CI -0.34, -0.11) µm2 for area, -0.06 (95% CI -0.09, -0.03) µm for length and -0.09 (95% CI -0.19, -0.06) µm for perimeter. Fine particulates were also associated with 1.03 (95% CI 0.40, 1.66) greater percent sperm head with acrosome.ConclusionsAir pollution exposure was not associated with semen quality, except for sperm head parameters. Moderate levels of ambient air pollution may not be a major contributor to semen quality.
| S-EPMC5878741 | biostudies-literature
Project description:The FecXR mutation is a variant of the ovine gene BMP15 in the Rasa Aragonesa breed. Information on the physiological importance of carrying the FecX polymorphism in rams is limited. The aim of this study was to compare semen quality, testicle characteristics, and fertility rate of rams that carry the FecXR allele. Rams (n = 15) were either FecXR allele carriers (n = 10) or non-carriers, wild type (++) (n = 5). FecXR rams exhibited higher mass motility (p < 0.05), proportion of rapid sperm (p < 0.05), and a lower proportion of slow sperm (p < 0.0001) than did ++ rams. The presence of the FecXR allele was not associated with mean scrotal circumference or testicular length and diameter, although season had a significant (p < 0.05) effect on these traits. Genotype (p < 0.05) and season (p < 0.01) had a significant effect on mean fertility rate, FecXR rams had a higher proportion of pregnant ewes than did ++ rams (p < 0.05). In conclusion, the FecXR allele produced high-quality semen throughout the year, and corresponded with an improvement in some sperm parameters, particularly, mass motility and the proportion of rapid sperm.
| S-EPMC7552265 | biostudies-literature
Project description:PurposeSuperoxide dismutase (SOD) is an important component of antioxidative defense systems and plays an important role in protecting spermatozoa from oxidative damage. In this study, we assessed seminal SOD activity, its association with semen parameters, and also genetic and non-genetic factors contributing to the determination of SOD activity in infertile men.MethodsSemen samples were obtained from 435 male infertility patients. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay. Four single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 genes were genotyped using OpenArray platform.ResultsWe found that seminal SOD activity was positively associated with sperm concentration and overall motility, whereas inversely with sperm DNA fragmentation. In addition, infertile men with SOD2 rs4880 CC variants showed a low level of SOD activity when compared with TT carriers (Mean ± SD: 268.3 ± 102.3 and 342.8 ± 98.2, respectively, P = 0.005). Those who consumed vitamin C/E (≥3 times per week) had a significantly higher SOD activity level than those who did not (mean ± SD: 379.8 ± 93.3 and 332.2 ± 94.9, respectively, P = 0.001).ConclusionsSeminal SOD activity and other factors influencing SOD activity play a role in determining sperm fertilization potential and male infertility.
| S-EPMC4016371 | biostudies-literature
Project description:Study questionWhat are the relations among birthweight (BW), semen parameters and birth outcomes in a population-based sample?Summary answerBW is unrelated to semen parameters, which are in turn unrelated to birth outcomes.What is known alreadyIn clinical settings, there has been suggestion that semen parameters are related to BW when comparing fertile and infertile men; however, findings have been less clear in more general populations.Study design, size, durationQuestionnaire data and semen samples were collected at baseline from 427 male participants of the population-based Longitudinal Investigation of Fertility and the Environment (LIFE) prospective cohort study from 2005 to 2009, who were followed prospectively to assess pregnancy outcomes among 226 singleton births.Participants/materials, setting, methodsMen of at least 18 years of age who were married or in a committed relationship and trying to conceive were eligible for participation; physician-diagnosed infertility was an exclusion criterion. Participants were recruited from two geographic areas and semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure using methods including computer-aided semen analysis integrated visual optical system and sperm chromatin structure assay. Linear and mixed models were used for statistical analysis of the relations between men's BW, semen parameters, and BW, gestational age at delivery, birth length, head circumference and ponderal index of singleton births.Main results and the role of chanceNo association was observed between male BW and semen parameters or birth outcomes. Few associations were observed between semen parameters and birth outcomes, and the observed statistically significant associations were isolated and without a consistent pattern that would suggest an association between BW and birth outcomes.Limitations, reasons for cautionMen's BW was self-reported and may be subject to some imprecision. Semen analysis was performed the day after collection, an approach that impacts the assessment of motility and that may limit inference from our analyses of motility measures. In addition, inclusion criteria for selection into the cohort limits generalizability to generally healthy couples trying to conceive and without known subfertility.Wider implications of the findingsDespite suggestions from prior studies of male in utero exposures impacting BW and male reproductive health, there appears to be little support for such relations in this generally healthy population.Study funding/competing interest(s)Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358). The authors report no competing interests, and a Memo of Understanding with the National Institute of Occupational Safety and Health (NIOSH) for semen analysis.Trial registration numberNot applicable.
| S-EPMC5400075 | biostudies-literature