Yoshihito Sasaki

Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest

AbstractGenetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Mouse meiotic mutant mei1 (meiosis defective 1) was isolated by a screening of infertile mice. Male mei1 mice have azoospermia due to meiotic arrest, and the mouse Mei1 gene is responsible for the mei1 phenotype. To investigate whether human MEI1 gene defects are associated with azoospermia by meiotic arrest, we isolated the human MEI1 cDNA based on the mouse Mei1 amino acid sequence. MEI1 is expressed specifically in the testis. Mutational analysis by direct sequencing of all MEI1 coding regions was performed in 27 men (13 European Americans, 13 Israeli and 1 Japanese) having azoospermia due to complete early meiotic arrest. This identified four novel, coding single-nucleotide-polymorphisms (cSNPs), i.e., SNP1 (T909G), SNP2 (A1582G), SNP3 (C1791A) and SNP4 (C2397T) in exons 4, 8, 9 and 14, respectively. Using these cSNPs, an association study was carried out between 26 non-Japanese patients with azoospermia and two sets of normal control men (61 normal European Americans and 60 Israelis). Consequently, SNP3 and SNP4 were shown to be associated with azoospermia among European Americans (P =0.0289 and P =0.0299 for genotype and allele frequencies at both the polymorphic sites, respectively), although no such association was observed among Israelis (P >0.05). Haplotype estimation revealed that the frequencies of SNP3-SNP4 (C-T), SNP3-SNP4 (A-C) and SNP3-SNP4 (A-T) were higher in the European American patients, and the frequency of SNP3-SNP4 (A-T) was also higher than in both control groups. These results suggest that MEI1 may play a role in meiosis during spermatogenesis, especially in European Americans.

VIBE MRI for Evaluating the Normal and Abnormal Gastrointestinal Tract in Fetuses

OBJECTIVE The great potential of MRI for assessing gastrointestinal abnormalities in fetuses has been described. T1-weighted images may add additional information to T2-weighted images in diagnosing fetal gastrointestinal abnormalities. The objective of this study was to assess the performance of a 3D volumetric interpolated breath-hold sequence (VIBE) in evaluating the normal and abnormal fetal gastrointestinal tract. CONCLUSION VIBE provides high-quality T1-weighted and 3D MR colonography images for the evaluation of the normal and abnormal gastrointestinal tract in fetuses, and 3D MR colonography provides excellent delineation of the meconium.

Association of antenatal corticosteroids and the mode of delivery with the mortality and morbidity of infants weighing less than 1,500g at birth in Japan.

Objective: This study aimed to re-evaluate the effectiveness of antenatal corticosteroids (ACS) and to analyze the association between ACS and the mode of delivery in the context of perinatal morbidity and mortality in very-low-birth-weight (VLBW) infants. Study Design: This retrospective cohort study involved 15,765 VLBW infants born between 2003 and 2008 at less than 34 weeks of gestation and weighing less than 1,500 g at birth. Data were obtained from the Japanese neonatal research network database. Univariate and multivariate logistic regression analyses were performed to evaluate the impact of ACS and mode of delivery on the risk of infant mortality and morbidity. Results: Administration of ACS was associated with decreases in mortality rate, intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP), and was not associated with the incidence of respiratory distress syndrome (RDS), periventricular leukomalacia or necrotizing enterocolitis (NEC). When the administration of ACS was analyzed in the context of different modes of delivery, the incidence of IVH and ROP tended to decrease with cesarean section deliveries, whereas the incidence of RDS tended to decrease and the incidence of NEC tended to increase for infants delivered vaginally. The incidence of chronic lung disease tended to increase in association with both delivery methods. Conclusions: This large cohort study reconfirms that ACS treatment is associated with decreases in infant mortality and severe morbidity. Furthermore, the delivery method may be associated with severe morbidity in VLBW infants exposed to ACS.

Short Communication: Isolation and Expression Analysis of the Testis-Specific Gene, Human OPPO1

AbstractPurpose: To investigate human spermatogenesis, we isolated human testis-specific genes. Methods: Using mouse amino acid sequences, we found the region including homology in amino acid level in the human genome sequences. The primers encompassing introns were made and RT-PCR and RACE were carried out. The resultant PCR products were sequenced. Results: The full-length cDNA of human OPPO1 was isolated. It encodes 257 amino acid residues. The expression of the human OPPO1 was predominantly in the testis. On the other hand, partial cDNAs of ZNF8, GR194, GR219, GR093, GR046, GR163, and GR200 were expressed in the various tissues. Conclusions: Our data suggests that the human OPPO1 may play important roles in human spermatogenesis.

GATM, the human ortholog of the mouse imprinted Gatm gene, escapes genomic imprinting in placenta

The GATM gene encodes L-arginine:glycine amidinotransferase, which catalyzes the conversion of L-arginine into guanidinoacetate, the rate-limiting step in the synthesis of creatine. Since, deficiencies in creatine synthesis and transport lead to certain forms of mental retardation in human, the human GATM gene appears to be involved in brain development. Recently it has been demonstrated that the mouse Gatm is expressed during development and is imprinted with maternal expression in the placenta and yolk sac, but not in embryonic tissues. We investigated the imprinting status of the human GATM by analyzing its expression in four human placentas. GATM was biallelically expressed, thus suggesting that this gene escapes genomic imprinting in placentas, differently from what has been reported in mouse extra-embryonic tissues.

Application of the perfusion index in obstetric bleeding

Abstract Objective: We assessed the utility of the pulse oximeter perfusion index (PI) in maternal monitoring immediately after delivery. Methods: We examined 30 pregnant women without any complications using the Rad7 device at delivery. The correlations between heart rate (HR), systolic blood pressure (BP), oxygen saturation SpO2, PI, Pleth variability index (PVI), shock index and blood loss were assessed. Results: Blood loss at 20-min postpartum was not correlated with the difference in heart rate, systolic BP, SpO2, shock index or PVI taken immediately after delivery and at 20-min postpartum, but showed a strong negative correlation with the difference in the PI taken immediately after delivery and at 20-min postpartum (r = −0.70). Conclusion: PI changes were correlated with post-delivery blood loss and can be used for maternal monitoring at delivery.

The human transcript induced in spermatogenesis 50

Background and AimsRecently, a number of genes that are expressed specifically in the testis have been identified in rat and mouse. In 2002, 80 transcript induced in spermatogenesis (Tisp) genes with this specific expression were isolated in mice. In the human, however, the number of such genes isolated is much lower. The aim of this study therefore was the isolation of human genes specifically expressed in testis.MethodsWe searched for human genome region with homology to the mouse Tisp gene family at the amino acid level using GenBank. The primers were made in human homologous regions, and polymerase chain reaction analysis was performed with templates using cDNA libraries of a range of human tissues. The cDNA specifically expressed in testis were isolated and detailed expression analysis was performed.ResultsThe 28 human TISP related genes were analyzed. Five of these genes were not expressed in testis and only three, TISP50, TISP15 and TISP43 related gene, were expressed specifically in testis. The cDNA of these three genes were isolated.ConclusionExpression analysis demonstrated that there is some discrepancy between human and mouse for the TISP gene family. From expression patterns and amino acid sequences, it is suggested that the human TISP50, TISP15 and TISP43 related genes play some critical roles in spermatogenesis.

Molecular cloning and expression analysis of the mouse Spot-2 gene in pituitary development

Mouse Spot-1 is a DNA-binding protein with a domain (His-Thr) encoded by p(CA)n repeats. Spot-1 interacts with the nuclear localization signal (NLS) I of p53 through its His-Thr domain. In this study we describe the cloning and expression patterns of a novel gene encoding a protein containing a His-Thr domain, Spot-2. Spot-2 is exclusively expressed in the pituitary from stage E13.5 to E15.5. Mouse Lhx3 plays a critical role during early organogenesis in the pituitary. The Spot-2 gene appears to be a downstream gene of Lhx3. It is suggested that Spot-2 plays important roles in pituitary development.