Swimming Suppresses Cognitive Decline of HFD-Induced Obese Mice through Reversing Hippocampal Inflammation, Insulin Resistance, and BDNF Level.

Obesity is an important public health problem nowadays. Long-term obesity can trigger a series of chronic diseases and impair the learning and memory function of the brain. Current studies show that scientific exercise can effectively improve learning and memory capacity, which also can provide benefits for obese people. However, the underlying mechanisms for the improvement of cognitive capacity under the status of obesity still need to be further explored. In the present study, the obesity-induced cognition-declined model was established using 4-week-old mice continuously fed with a high-fat diet (HFD) for 12 weeks, and then the model mice were subjected to an 8-week swimming intervention and corresponding evaluation of relevant indicators, including cognitive capacity, inflammation, insulin signal pathway, brain-derived neurotrophic factor (BNDF), and apoptosis, for exploring potential regulatory mechanisms. Compared with the mice fed with regular diets, the obese mice revealed the impairment of cognitive capacity; in contrast, swimming intervention ameliorated the decline in cognitive capacity of obese mice by reducing inflammatory factors, inhibiting the JNK/IRS-1/PI3K/Akt signal pathway, and activating the PGC-1α/BDNF signal pathway, thereby suppressing the apoptosis of neurons. Therefore, swimming may be an important interventional strategy to compensate for obesity-induced cognitive impairment.

[Target gene panel method versus whole-exome sequencing in detection of idiopathic hypogonadotropic hypogonadism in males].

Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method. METHODS: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method. RESULTS: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%. CONCLUSIONS: For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.

[Correlation between microRNA-34b/c single nucleotide polymorphism rs4938723 and male infertility].

OBJECTIVE: To investigate the relationship between microRNA-34b/c single nucleotide polymorphism (SNP) rs4938723 and the risk of male infertility. METHODS: This case-control study included 553 males aged 19－40 (29.42 ± 5.09) years with idiopathic infertility, 153 with azoospermia and 400 with oligoasthenospermia, and another 332 normal fertile men aged 19－40 (28.5 4 ± 4.63) years as controls. We collected the clinical data and peripheral blood samples from the subjects, genotyped microRNA-34b/c rs4938723 by Sequenom MassARRAY, and analyzed the relationship between the genotypes of microRNA-34b/c rs4938723 and the risk of male infertility using the logistic regression model. RESULTS: Statistically significant differences were observed between the infertility patients and normal controls in sperm concentration (ï¼»18.71 ± 15.19ï¼½ vs ï¼»79.91 ± 43.96ï¼½ × 106/ml, P < 0.01), the percentage of progressively motile sperm (ï¼»13.27 ± 24.52ï¼½% vs ï¼»42.82 ± 8.86ï¼½%, P < 0.01) and the level of follicle stimulating hormone (ï¼»16.09 ± 17.37ï¼½ vs ï¼»12.20 ± 4.73ï¼½ IU/L, P < 0.01). Compared with the TT genotype, the TC and CC genotypes showed no correlation with male infertility, nor did the genetic locus in the subgroup analysis. CONCLUSIONS: No correlation was found between microRNA-34b/c SNP rs4938723 and male infertility, which, however, needs to be further verified by larger-sized samples.

[Detection of DPY19L2 gene mutation in 2 cases of globozoospermia].

OBJECTIVE: To investigate the mutation of the DPY19L2 gene in patients with globozoospermia. METHODS: We collected the clinical data and peripheral blood from 2 patients with globozoospermia and screened for mutation of the DPY19L2 gene by PCR amplification and DNA sequencing technology. RESULTS: The sperm from the 2 globozoospermia patients were round morphologically under the light microscope, with deeply stained nuclei but no acrosome. Electron microscopy showed the sperm with a large round head but no acrosomal structure, the nuclei enveloped by a single layer of membrane and the cytoplasm dispersed. PCR amplification revealed homozygous deletion of Exon 5, Exon6 and Exon15 in the DPY19L2 gene in both the patients. CONCLUSIONS: This study proved that the homozygous mutation of DPY19L2 could lead to globozoospermia, which has an important significance for researches on the molecular mechanisms and gene diagnosis of the disease as well as for clinicians in genetic counseling and treatment.

[Correlation between CFTR 5T polymorphisms and the risk of congenital bilateral absence of the vas deferens].

OBJECTIVE: To investigate the association between the 5T site polymorphism of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the risk of congenital bilateral absence of the vas deferens (CBAVD). METHODS: This case-control study included 40 male patients with isolated CBAVD in the experimental group and 104 healthy men as controls. We used the Sanger sequencing method to encode the CFTR gene intron 9 (TG) m-n(T) and type the haplotypes, followed by a review and meta-analysis of the data obtained from the experiment and relevant literature from the PubMed, Web of science, Medline, CNKI and an exploration of the correlation between 5T mutation and the risk of CBAVD. RESULTS: Sanger sequencing revealed 6 genotypes in the CBAVD patients, including TG11-5T, TG12-5T, TG13-5T, TG11-7T, TG12-7T and TG11-9T, and 7 in the healthy controls, which were TG11-5T, TG12-5T, TG10-7T, TG11-7T, TG12-7T, TG13-7T and TG11-9T. Compared with the controls, the CBAVD patients showed obviously increased rates of the TG12-5T haplotype (4.81% ［10/208］ vs 16.25% ［13/80］) and the TG13-5T haplotype (0% vs 7.5% ［6/80］), but no significant difference in the TG11-5T haplotype (1.92% ［4/208］ vs 2.50% ［2/80］). There was a statistically significant difference between the experimental and control groups in the TG12_13-5T haplotype (OR = 7.40, 95% CI: 4.83－11.34, P < 0.01). The TG12_13-5T haplotype was found to be highly correlated with CBAVD. CONCLUSIONS: The haplotype of TG12_13-5T increases the risk of CBAVD in men, which has provided a theoretical basis for male reproduction.

[Correlation of single nucleotide polymorphisms rs995030 and rs4474514 of the KITLG gene with male infertility].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms rs995030 and rs4474514 of the tyrosine kinase receptor-specific ligand (KITLG) gene with the risk of male infertility. METHODS: This study included 360 patients with idiopathic male infertility and 338 healthy fathers as controls, all from the surrounding areas of Nanjing. According to the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, we divided the infertility patients into an azoospermia (n = 143), a severe oligozoospermia (n = 159), and an oligozoospermia group (n = 58). We obtained the basic clinical data on all the subjects, collected genomic DNA from the peripheral blood of the patients, determined the genotypes of the KITLG gene rs995030 and rs4474514 by sequence mass-array, and analyzed the correlation between the two-point gene polymorphism and male infertility by logistic regression analysis. RESULTS: Statistically significant differences were observed between the infertility patients and normal fertile controls in sperm concentration (ï¼»13.23 ± 24.52ï¼½ vs ï¼»78.74 ± 61.25ï¼½ ×106/ml, P < 0.01), the percentage of progressively mobile sperm (ï¼»18.71 ± 15.19ï¼½% vs ï¼»39.36 ± 9.75ï¼½%, P < 0.01), and the level of FSH (ï¼»16.09 ± 17.31ï¼½ vs ï¼»4.56 ± 2.41ï¼½ IU/L, P < 0.01), but not between the genotypes and male infertility, and no correlation was found in subgroup analysis. CONCLUSIONS: The single nucleotide polymorphisms rs995030 and rs4474514 of the KITLG gene were not significantly correlated with male infertility, which is to be further verified by more studies with samples of larger size and expanded selection range.

[Correlation of the single nucleotide polymorphism rs662 of PON1 with the risk of male infertility].

Objective: To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility. METHODS: This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model. RESULTS: Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (ï¼»16.30 ± 17.76ï¼½ vs ï¼»4.72 ± 2.51ï¼½ U/L, P < 0.01) but a decreased percentage of progressively motile sperm (PMS) (ï¼»7.40 ± 14.17ï¼½ % vs ï¼»41.93 ± 9.06ï¼½ %, P < 0.01) and sperm concentration (ï¼»2.74 ± 3.64ï¼½ vs ï¼»75.83 ± 63.66ï¼½ ×106/ml, P < 0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63－1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56－1.34, P = 0.525). CONCLUSIONS: The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.

[Correlation of the single nucleotide polymorphisms rs34349826 and rs6521 of the LHB gene with male infertility in Chinese men].

Objective: To study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men. METHODS: This case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software. RESULTS: There were statistically significant differences between the control and infertility groups in the semen volume (ï¼»3.51 ± 1.36ï¼½ vs ï¼»3.74 ± 1.71ï¼½ ml, P <0.05), sperm concentration (ï¼»79.21 ± 61.60ï¼½ vs ï¼»27.37 ± 30.80ï¼½ ×106/ml, P <0.01), percentage of progressively motile sperm (ï¼»39.40 ± 9.64ï¼½ % vs ï¼»11.90 ± 14.72ï¼½ %, P <0.01), and levels of serum luteinizing hormone (LH) (ï¼»3.29 ± 1.39ï¼½ vs ï¼»6.25 ± 4.83ï¼½ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (ï¼»4.56 ± 2.31ï¼½ vs ï¼»15.64 ± 17.03ï¼½ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility. CONCLUSIONS: The rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.

[Multiplex fluorescence PCR for detection of Y Chromesome microdeletions].

OBJECTIVE: Detection of azoospermia factor (AZF) microdeletions on the Y chromosome is one of the auxiliary strategies recognized at home and abroad for the examination of male infertility. Traditional PCR gel electrophoresis fails to meet the clinical needs due to its shortcomings. The purpose of this study was to explore the feasibility of multiplex fluorescence PCR in the detection of AZF microdeletions. METHODS: We collected samples of Y chromosomal AZF microdeletions from 238 patients with azoospermia or oligozoospermia and 62 normal males, identified the 14 short tandem repeat (STR) loci in the AZF region of the Y chromosome by multiplex PCR gel electrophoresis and multiplex fluorescence PCR, and analyzed the consistency in the results of the two methods by Kappa test. RESULTS: There was a perfect consistency between multiplex PCR gel electrophoresis and multiplex fluorescence PCR in the detection rate of the STR loci in the 300 samples. Kappa test showed both P and Kappa values to be 1 for the 6 loci in the AZFa, AZFb and AZFc regions of the Y chromosome, with no statistically significant difference between the two methods. CONCLUSIONS: Multiplex fluorescence PCR can save a lot of time, reduce workload and improve laboratory efficiency and therefore is preferable to multiplex PCR gel electrophoresis in detecting Y chromosome microdeletions.

Novel mutations in COL4A3, COL4A4, and COL4A5 in Chinese patients with Alport Syndrome.

Alport syndrome (AS) is a clinically and genetically heterogeneous, progressive nephropathy caused by mutations in COL4A3, COL4A4, and COL4A5, which encode type IV collagen. The large sizes of these genes and the absence of mutation hot spots have complicated mutational analysis by routine polymerase chain reaction (PCR)-based approaches. Here, in order to design a rapid and effective method for the genetic diagnosis of AS, we developed a strategy by utilizing targeted capture associated with next-generation sequencing (NGS) to analyze COL4A3, COL4A4, and COL4A5 simultaneously in 20 AS patients. All the coding exons and flanking sequences of COL4A3, COL4A4, and COL4A5 from the probands were captured followed by HiSeq 2500 sequencing. Candidate mutations were validated by classic Sanger sequencing and quantitative (q)PCR. Sixteen patients (16/20, 75%) showed X-linked inheritance, and four patients (4/20, 20%) showed autosomal recessive inheritance. None of the individuals had autosomal-dominant AS. Fifteen novel mutations, 6 known mutations, and 2 novel fragment deletions were detected by targeted capture and NGS. Of these novel mutations, 12, 3, and 2 mutations were detected in COL4A5, COL4A4, and COL4A3, respectively. A comparison of the clinical manifestations caused by different types of mutations in COL4A5 suggested that nonsense mutations and glycine substitution by an acidic amino acid are more severe than the other missense mutations. Pathogenic mutations were detected in 20 patients. These novel mutations can expand the genotypic spectrum of AS. Our results demonstrated that targeted capture and NGS technology are effective in the genetic diagnosis of AS.

[Single nucleotide polymorphism of the TP53 gene is not correlated with male infertility].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphism (SNP) rs1042522 of the tumor protein p53 (TP53) gene with the risk of male infertility. METHODS: This casecontrol study included 380 male patients with idiopathic infertility and 398 normal fertile men as controls from the Nanjing area. We genotyped the SNP rs1042522 of the TP53 gene by Sequence Mass Array and analyzed the correlation of the SNP with male infertility using the logistic regression model. RESULTS: Compared with the normal controls, the patients with idiopathic infertility showed significantly decreased sperm concentration (ï¼»77.34±49.24ï¼½ vs ï¼»13.13±24.96ï¼½ ×106/ml), percentage of progressively motile sperm (ï¼»42.55±9.57ï¼½ vs ï¼»10.38±5.57ï¼½%), serum testosterone level (ï¼»14.07±5.36ï¼½ vs ï¼»11.89±4.50ï¼½ nmol/L), and folliclestimulating hormone level (ï¼»16.80±18.20ï¼½ vs ï¼»4.55±7.17ï¼½ U/L) (P < 0.05) but no statistically significant differences in other parameters. No correlation was observed between the SNP frequencies and male infertility and similar results were found in the subgroups of the cases. CONCLUSIONS: SNP rs1042522 of the TP53 gene is not significantly correlated with the risk of male infertility.

[Nucleotide polymorphism rs4880 of the SOD2 gene and the risk of male infertility].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphism (SNP) rs4880 of the superoxide dismutase 2 (SOD2) gene with the risk of male infertility. METHODS: This casecontrol study included 519 male patients with idiopathic infertility (aged 19－40 ï¼»28.93±4.93ï¼½ years) in the case group and 338 fertile men (aged 19－40 ï¼»28.40±4.25ï¼½ years) in the control group. We collected the clinical data, genotyped the SNP rs4880 of the SOD2 gene by Sequenom Mass Array, and analyzed the association of different genotypes with male infertility using the logistic regression model. RESULTS: Statically significant differences were observed between the case and control groups in the level of folliclestimulating hormone (FSH) (ï¼»4.72±2.51ï¼½ vs ï¼»15.65±17.24ï¼½ U/L, P< 0.01), the percentage of progressively mobile sperm (ï¼»9.12±13.5ï¼½ vs ï¼»41.95±9.03ï¼½%, P< 0.01), and sperm concentration (ï¼»12.95±24.38ï¼½ vs ï¼»72.88±45.60ï¼½ ×106/ml, P< 0.01), but not in other parameters. No correlation was found between male infertility and the heterozygous genotype TC (OR = 0.90, 95% CI: 0.65－1.25, P = 0.516) or the homozygous genotype CC (OR=1.49, 95% CI: 0.38－5.81, P = 0.566) as compared with the wild genotype TT, and similar results were obtained in the analysis of the subgroups. CONCLUSIONS: The SNP rs4880 of the SOD2 gene was not correlated with male infertility, which, however, is to be supported by further studies with larger samples from more areas.

[Kallmann syndrome with deafness caused by SOX10 mutation: Advances in research].

The transcription factor SOX10, as a major actor in the development of the neural crest, plays a key role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation. Abnormalities of neural crest development in humans lead to a number of genetic diseases known as neurocristopathies or neural crest disorders. The mutation of SOX10 can cause Kallmann syndrome (KS), which is a clinically and genetically heterogeneous condition and defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Since then, there have been a number of related reports that mutation of SOX10 will lead to KS with deafness. This review focuses on the SOX10 gene and the advances in the diagnosis and genetic studies of KS with deafness caused by the mutatuin of SOX10.

[Relationship between the FSHR Thr307Ala-Asn680Ser gene polymorphism and male infertility: A meta-analysis].

OBJECTIVE: To assess the association of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility. METHODS: We searched Pubmed, EMBASE, Web of Science, CNKI, and WANFANG databases for literature on the correlation of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility published from 2005 to the present time. According to the inclusion criteria, we included 12 epidemiological case-control studies and subjected them to a comprehensive analysis with the Stata11.0 software. RESULTS: A total of 2 893 male infertility patients and 3 312 controls were involved in the 12 studies. The Thr307Ala (rs6165) gene polymorphism was shown to be a risk factor for male infertility among the three comparison models (homozygous comparison model, hybrid comparison model and dominant comparison model), with the pooled odds ratios (OR) of 1.26 (95% CI: 1.03－1.54, P = 0.023), 1.18 (95% CI: 1.03－1.36, P = 0.018), and 1.20 (95% CI: 1.05－1.37, P = 0.006), respectively. And the Asn680Ser(rs6166) polymorphism was a risk factor for male infertility in the homozygous comparison and recessive comparison models, with the pooled ORs of 1.24, (95% CI: 1.05－1.45, P = 0.009) and 1.20 (95% CI: 1.04－1.39, P = 0.013), respectively. Layered meta-analysis showed that in the homozygous comparison model, the Thr307Ala-Asn680Ser polymorphism is a risk factor for male infertility in the white population, with the OR of 1.37 (95% CI: 1.03－1.82, P = 0.003) and 1.21 (95% CI: 1.00－1.47, P = 0.048), respectively. CONCLUSIONS: In the homozygous model (GG vs AA), the FSHRThr307Ala-Asn680Ser gene polymorphism might be a protective factor against male infertility.

[CYP1A1 rs4646422 gene polymorphisms not correlated with male infertility in Chinese Han population].

OBJECTIVE: To determine the correlation of the CYP1A1 (rs4646422) gene polymorphisms with male infertility in the Chinese Han population. METHODS: Using the Mass ARRAY iPLEX GOLD technique, we conducted a case-control study on theCYPlA1 (rs4646422) gene polymorphisms in 636 infertile males aged 21-49 years (case group) and 442 normal healthy men aged 23-47 years (control group) of the Chinese Han population. We analyzed the genotypes and allele frequencies in the two groups ofsubjects with the SPSS 20.0 software. RESULTS: Compared with the wild homozygous genotype GG, the heterozygous genotype AG (OR = 1.06, 95% CI 0.81-1.38) and homozygous genotype AA (OR = 1.11, 95% CI 0.56-2.21) showed no correlation with male infertility, nor did the mutant allele A (OR = 1.06, 95% CI 0.85-1.32) in comparison with the wild allele G. CONCLUSION: The CYP1A1 (rs4646422) gene polymorphisms might not be correlated with male infertility in the Chinese Han population.

[Single nucleotide polymorphisms of the N-acetyltransferase 2 gene not correlated with male infertility].

Objective: To investigate the correlation of the single nucleotide polymorphisms（SNPs） rs1799930 and rs1799931 of the N-acetyltransferase 2 gene（ NAT2） with the risk of male infertility in Nanjing area. Methods: We made a case-control study of 636 cases of male idiopathic infertility and 442 normal fertile men as controls. We genotyped the two SNPs by Sequenom Mass Array, analyzed the correlation of different genotypes with male infertility using the logistic regression model, and determined the association of the linkage effect of the two SNPs with male infertility by haplotype analysis. Results: Statistically significant differences were found between the case and control groups in sperm concentration（[32. 32 ± 45. 49] vs [72. 77 ± 45. 21] × 106/ ml, P < 0. 01）,the percentage of progressively motile sperm（[15. 29 ± 5. 06] vs [42. 02 ± 9. 04]%,P < 0. 01）,and the level of follicle-stimulating hormone（[14. 69 ± 12. 37] vs [4. 72 ± 2. 51] U / L,P < 0. 01), but not in other parameters. No correlation was observed between the frequencies of the two SNPs or alleles in different models and male infertility. Haplotype analysis suggested a linkage effect within rs1799930 and rs1799931（D' = 0. 998,r2= 0. 05） but no evident correlation between male infertility and genotype combination. Conclusion: The SNPs rs1799930 and rs1799931 of the NAT2 gene were not found to be correlated with the risk of idiopathic infertility in men.

[Androgen receptor gene polymorphisms and male infertility].

The androgen receptor (AR), as a ligand-dependent transcription protein and a member of the steroid receptor superfamily widely present in the body, is involved in the adjustment of the function of androgens and plays an important role in spermatogenesis. Androgens participate in spermatogenesis by binding AR and initiating the expression of the target gene. The polymorphisms of the AR gene may change the structure of AR and affect its avidity of binding androgens, making their downstream target genes unable to transcribe proteins. With the development of DNA sequencing techniques, studies on the association of the polymorphisms of the AR gene with male infertility have become a hot topic.

A duplication upstream of SOX9 was not positively correlated with the SRY­negative 46,XX testicular disorder of sex development: A case report and literature review.

The 46,XX male disorder of sex development (DSD) is rarely observed in humans. Patients with DSD are all male with testicular tissue differentiation. The mechanism of sex determination and differentiation remains to be elucidated. In the present case report, an 46,XX inv (9) infertile male negative for the sex­determining region of the Y chromosome (SRY) gene was examined. This infertile male was systemically assessed by semen analysis, serum hormone testing and gonadal biopsy. Formalin­fixed and paraffin­embedded gonad tissues were assessed histochemically. The SRY gene was analyzed by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR). The other 23 specific loci, including the azoospermia factor region on the Y chromosome and the sequence-targeted sites of the SRY­box 9 (SOX9) gene were analyzed by PCR. The genes RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 were also assessed using sequencing analysis. Affymetrix Cytogenetics Whole Genome 2.7 M Arrays were used for detecting the genomic DNA from the patient and the parents. The patient with the 46,XX inv (9) (p11q13) karyotype exhibited male primary, however, not secondary sexual characteristics. However, the patient's mother with the 46, XX inv (9) karyotype was unaffected. The testicular tissue dysplasia of the patient was confirmed by tissue biopsy and absence of the SRY gene, and the other 23 loci on the Y chromosome were confirmed by FISH and/or PCR. The RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 genes were sequenced and no mutations were detected. A duplication on the 3 M site in the upstream region of SOX9 was identified in the patient as well as in the mother. The patient with the 46,XX testicular DSD and SRY­negative status was found to be infertile. The duplication on the 3 M site in the upstream region of SOX9 was a polymorphism, which indicated that the change was not a cause of 46,XX male SDS. These clinical, molecular and cytogenetic findings suggested that other unidentified genetic or environmental factors are significant in the regulation of SDS.

A patient with unusual features and a 69.5 Mb duplication from a de novo extra der (9): a case report.

Partial trisomy 9 is a common autosomal trisomy, which is characterized by non-specific psychomotor delay, mental retardation and moderately abnormal characteristic facial features. Generally, partial trisomy 9 leads to variable phenotypes depending on the size and position of the duplicated region. However, a precise genotype/phenotype map has not been determined. The present study reports the case of a 3-year-old female with certain typical features of trisomy 9p syndrome, who presented with a number of the distinctive symptoms, as well as sensorineural hearing loss, which has not previously been associated with this trisomy. Karyotype, M­FISH and OaCGH analysis were performed on the patient and her parents. The final karyotype was determined to be 47, XX, +mar.ish der (9) (wcp9+). arr cgh 9pterq21.12 (DOCK8 → LOC138225)x3. Cytogenetic results showed a de novo extra der (9) with 69.5 Mb duplication. Although the molecular mechanism underlying the hearing loss is unclear, it was proposed that the 9q13 → 9q21 region may be critical for hearing.

[FSH and FSHR gene polymorphisms and male infertility: An update].

Follicle-stimulating hormone (FSH) is synthesized and secreted by the anterior pituitary, which binds to its receptors expressed on the membrane of Sertoli cells in the testis to bring about spermatogenesis. With the development of DNA sequencing technology, FSH SNPs rs10835638 and FSHR SNPs rs6165, rs6166, and rs1394205 were detected, which might directly affect the expression of FSH and activity of FSHR, resulting in male spermatogenic dysfunction. This review focuses on the relationship of FSH and FSHR gene polymorphisms with male infertility.