Kazuhide Ogita

Mouse model of human infertility : Transient and local inhibition of endometrial STAT-3 activation results in implantation failure

Embryo implantation involves a series of biochemical reactions and its failure is an important therapeutic target of infertility treatment. We established an infertile mouse model using transient and local suppression of signal transducer and activator of transcription‐3 (STAT‐3) activity by STAT‐3 decoy transfer into the uterine cavity during implantation, resulting in <30% implantation. This infertility is caused by suppression of decidualization, which is indispensable for implantation, and independent of progesterone. These conditions may mimic clinically unexplained infertility. Our results suggest that STAT‐3 could be a useful target for diagnosis and therapy of human implantation failure.

NF‐κB Activation at Implantation Window of the Mouse Uterus

Problem:  Nuclear factor kappa B (NF‐κB) is one candidate transcriptional modulator, which might regulate many kinds of molecules that play sequential roles at implantation in the endometrium. However, temporal and spatial activation of NF‐κB at implantation window is unknown.

Immunisation with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes in saline suppresses rodent fertility

Research into active immunisation against gonadotrophin releasing hormone (GnRH-I) has gained widespread acceptance as a means of controlling reproduction and behaviour of farm, companion and wild animals. Many studies describe the use of multiple copies of the self-peptide in linear alignment and conjugation with a large carrier protein to increase the immune response to the peptide. However, problems resulting from carrier protein epitope suppression have seen a diversion of interest into the use of genetic materials to elicit an optimum immune response. In this study, a 533-bp long DNA vaccine was constructed in pcDNAV5-HisB coding for 18.871 kDa GnRH-I-T-helper-V5 epitopes fusion protein. COS1 cells transfected with the vaccine construct were found to release fusion protein into culture supernatant. The vaccine construct (100 microg/mice) in saline solution administered into the anterior quadriceps muscle of ICR male and female mice stimulated antigen-specific IgG antibody responses. Testosterone levels in the vaccinated male mice were significantly (p = 0.021) reduced. A significant reduction in uterine implants were noted following mating between immunised males and control females (p = 0.028), as well as between immunised females and control males (p = 0.004). Histological examination of both the male and female gonads in study week 13 showed atrophy of the seminiferous epithelium and suppression of folliculogenesis.

Balloon tamponade during cesarean section is useful for severe post-partum hemorrhage due to placenta previa

Aim:  Severe post‐partum hemorrhage during cesarean section due to placenta previa is still one of the leading causes of maternal mortality. The aim of this study was to evaluate the efficiency of intrauterine tamponade with a Sengstaken‐Blakemore tube (SB‐tube) for the treatment of severe post‐partum hemorrhage in cases of placenta previa.

Effectiveness of Hormonal Tourniquet by Vasopressin during Myomectomy through Vasopressin V1a Receptor Ubiquitously Expressed in Myometrium

To elucidate the mechanism by which myometrial vasopressin injection promotes hemostasis during myomectomy, we examined the expression of vasopressin V1a receptor transcripts in the myometrium. Vasopressin V1a receptor expression was ubiquitous, and the transcripts were detected in the myometrium not only of cycling and pregnant patients, but also of postmenopausal or GnRH agonist-treated patients. Based on these observations, we applied intraoperative myometrial vasopressin injection during myomectomy in a non-randomized study in a total of 84 patients. Vasopressin injection significantly reduced the intraoperative blood loss and postoperative hemoglobin fall in patients without and with GnRH agonist pretreatment. No serious complications occurred on account of the vasopressin injection. We conclude that intraoperative vasopressin injection is effective as a hormonal tourniquet even in GnRH agonist-pretreated myomectomy.

Calcineurin/NFAT pathway: a novel regulator of parturition.

Problem  The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR‐deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized.

ORIGINAL ARTICLE: Calcineurin/NFAT Pathway: A Novel Regulator of Parturition

Problem  The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR‐deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized.

Rapid detection of trisomy 21 by gene dosage analysis using quantitative real‐time polymerase chain reaction

Aim:  Rapid detection of fetal aneuploidy helps inform a mother’s choice about the course of her pregnancy. Obtaining results by fluorescent in situ hybridization (FISH) requires more than 24 h, and thus a more rapid method is needed.

Molecular analysis of parturition via oxytocin receptor expression

In daily obstetric practice, oxytocin is one of the most frequently used drugs to stimulate uterine contraction. However, uterine sensitivity to oxytocin is profoundly different among pregnant women, which may reflect oxytocin receptor (OTR) expression in the uterus. We review here the literature focusing on OTR regulation in the human uterus. Recent progress in molecular biology has augmented our knowledge about OTR regulation in the uterus at the transcription level, although the totality of preparation for labor through OTR expression is still obscure.

Differential Expression and Localization of Decorin in Human Choriodecidual Membrane during Preterm and Term Pregnancy

Problem:  This study was aimed to isolate cDNAs for genes whose expression levels are dynamically regulated at the feto‐maternal interface around parturition.