OBJECTIVE: Nodal is a member of the transforming growth factor beta (TGF-beta) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury. MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells. RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha). CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.

Male infertility is mostly caused by spermatogenic failure. Currently, routine genetic analyses of unexplained azoospermia or oligozoospermia are limited to the investigation of Y chromosomal microdeletions and chromosome karyotype analyses. The aim of this study was to find spermatogenic failure genes in patients with chromosomal abnormalities and unexplained azoospermia caused by copy number variations in order to provide a theoretical basis for further research. Spermatogenic failure patients consisting of 13 males with chromosomal abnormalities and 20 with unexplained azoospermia were enrolled. The subjects underwent high-throughput genome-wide sequencing to find copy number variants (CNVs), and the results were analyzed using the Database of Genomic Variants, Online Mendelian Inheritance in Man database, and PubMed. The results showed that 16 CNVs were detected in 11 patients with chromosome abnormalities, and 26 CNVs were found in 16 males with azoospermia. Our data showed CNV-involved loci including: three times on 11p11.12 and 14q11.2 and twice on 6p21.32, 13q11, 15q11.11, 16p12.2, and 21q22.3. Some CNVs may involve changes in genetic structure and function or gene mutations, which may affect gene expression in testicular tissues and lead to spermatogenic failure. The involved genes include EDDM3A, EDDM3B, HLA-DRB1, HLA-DQA1, POTE B, GOLGA8C, DNMT3L, ALF, NPHP1, NRG1, RID2, ADAMTS20, TWF1, COX10, MAK, and DNEL1. By applying high throughput genome-wide sequencing to determine CNVs, we provide a number of candidate genes possibly contributing to spermatogenic failure.

A reciprocal translocation between the short arm of chromosome 1 and the long arm of chromosome 3 was observed in a pedigree of three carriers (proband, and his brother and mother).In this study, the three carriers had different clinical manifestations: the proband with infertility, his brother with spousal miscarriages, and his mother with no adverse reproductive history.Cytogenetic analysis of metaphase chromosomes was performed, and triple-color fluorescence in situ hybridization was applied to the detection of aneuploidy sperm related to the interchromosomal effect (ICE).An increase of aneuploidy of chromosome 21 in the proband and aneuploidy of chromosomes 13, 21, and Y in the brother were observed.Since patients with reciprocal translocations and spermatogenetic impairment are candidates, with their partners, for intracytoplasmic sperm injection, the study of the level of sperm aneuploidy rates would provide useful information for couples at risk, as well as contributing to a better understanding of the ICE.

Successful sperm retrieval from ejaculates of nonmosaic Klinefelter's syndrome (KS) patients by using semen cytology examination was described in this report. The clinical parameters of KS patients with sperm compared to patients without sperm were described. One hundred and fifty-one patients were proven to suffer from KS by chromosomal analysis using G-banding. Spermatozoa were obtained from 10 patients (10/151, 6.6%) using semen analysis. After semen cytology examination, 32 patients (32/151, 21.2%) were found to have sperm or germ cell in their ejaculate. The patients with successful sperm retrieval were significantly younger (27.1 ± 3.7 years) than the patients for whom sperm retrieval failed (28.9 ± 4.2 years). The mean serum testosterone level and the mean T/LH ratio of KS patients with successful sperm retrieval were significantly higher in men with sperm than in men without sperm (testosterone: 3.2 ± 2.1 ng/mL vs 2.7 ± 1.5 ng/mL; T/LH ratio: 0.2 ± 0.3 vs 0.1 ± 0.1). In conclusion, semen cytology examination should be performed to identify sperm and germ cells in the ejaculate of KS patients if no sperm can be detected by traditional semen analysis. The serum testosterone level and T/LH ratio revealed an association between impaired Leydig cell function and impaired spermatogenesis in KS males. KS patients should receive earlier diagnosis and treatment.

A 23-year-old woman who had experienced repeated stillbirths, was found to carry an additional segment on the long arm of the X chromosome. Array comparative genomic hybridization (aCGH) confirmed the origin of the 2 duplications (about 17.11 Mb). Thus, her karyotype was 46, X, dup (X) (q13.2-q21.1), dup(X) (q21.32-q22.1). We demonstrate that aCGH is a useful complementary tool to cytogenetic analysis for accurately determining banding. To our knowledge, this is the first case with normal apparently phenotype who inherited 2 duplications on Xq. Notably, after 2 stillbirths, she bore a healthy, normal female infant via natural pregnancy. Thus, a carrier of this karyotype can birth a phenotypically normal child.

The subsequent reproductive outcomes in couples with a history of recurrent pregnancy loss (RPL) associated with chromosome abnormalities or polymorphisms are generally not reported in China. Many RPL carrier couples have decided not to have children. The present study recorded the subsequent delivery, miscarriage, and unpregnancy outcomes of 113 RPL carrier couples and 226 non-carrier couples, and compared differences in reproductive outcomes between couples with different types of chromosome abnormalities or polymorphisms and chromosome normal couples. Our results showed that couples with RPL associated with parental chromosome abnormalities or polymorphisms did not have significantly lower live birth rates than non-carrier couples in China. These results suggest the current guidance given to Chinese RPL couples.

Y chromosome abnormalities are frequently associated with male infertility. Men with ring Y chromosomes can present with sexual infantilism, ambiguous genitalia, hypospadias, or azoospermia. AZF microdeletions can result in spermatogenic defects in such patients. Here, we report an unusual karyotype of 45,X/46,X,r(Y)/46,X,dic r(Y) in an azoospermic man. However, the reason for this patient's azoospermia is not an AZF microdeletion but might be the abnormal structure of the r(Y) chromosome, the 45,X cell line, mosaicism of the 3 cell lines, or another unknown cause. In such cases, if the couple wishes to reproduce, cytogenetic, molecular and fluorescent in situ hybridization evaluations should be performed, and preimplantation genetic diagnosis should be used together with assisted reproductive technology.

OBJECTIVE: To analyse the relationship between male infertility and chromosomal translocations, and the influence of different types of chromosomal translocations on semen quality, testicular volume and hormone levels. METHODS: A retrospective cohort of infertile men was recruited for chromosomal analysis using standard Giemsa stain banding. Physical examinations, semen analysis, hormonal analysis and the detection of azoospermia factor (AZF) microdeletions were carried out. Men with normal fertility were used as controls. RESULTS: Among the 1056 infertile men, 22 had chromosomal translocations (2.1%), including seven with Robertsonian translocations (0.7%), 11 with autosome-autosome reciprocal translocations (1.0%) and four with gonosome-autosome reciprocal translocations (0.4%). Left and right testicular volumes of patients with chromosomal translocations were significantly smaller than those in the fertile control group. There were no significant differences in hormone levels between patients with chromosomal translocations and fertile controls, except for significantly lower testosterone levels in patients with Robertsonian and gonosome-autosome reciprocal translocations compared with the controls. All AZF micro deletion analyses showed normal results. CONCLUSIONS: Chromosomal translocations may cause reductions in testicular volume and testosterone level, which may impact spermatogenesis, resulting in azoospermia Or oligozoospermia and male infertility.

This study investigated the effects of Ureaplasma urealyticum infection and raised seminal leucocyte levels on sperm morphology in 967 infertile males and 201 fertile healthy volunteers. U. urealyticum infection led to a significant decrease in the percentage of morphologically normal sperm in infertile males. There was a clear correlation between U. urealyticum infection, raised seminal leucocytes and abnormal sperm morphology. The percentage of morphologically normal sperm was significantly lower in U. urealyticum-positive than U. urealyticum-negative infertile males or fertile controls. The percentage of morphologically normal sperm was lowest in U. urealyticum-positive males with raised seminal leucocytes. Previous studies have found raised seminal leucocyte levels to be associated with reactive oxygen species. The authors suggest that oxidative stress contributes to the effects of U. urealyticum on sperm morphology. In conclusion, U. urealyticum infection can negatively affect sperm morphology and this study provided two possible mechanistic explanations.