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The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery., (© 2015 Wiley Publishing Asia Pty Ltd.)

Very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare and life-threatening disease characterized by an enzymatic defect in the fatty acid β-oxidation pathway. A nulliparous woman with VLCADD showed improvements in serum levels of the long-chain acylcarnitine moiety (C14:1) during pregnancy and successfully delivered a healthy infant vaginally. Pregnancy and vaginal delivery can be successfully completed in patients with VLCADD with careful management., (© 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.)

Objective: To investigate the differences in toll-like receptor (TLR)-mediated immune responses between human neonates and adults, focusing on the cytokine profiles of monocytes, dendritic cells (DCs), and monocyte-derived DCs (MoDCs) in cord and adult blood., Study Design: Purified monocytes, DCs, and MoDCs were stimulated with the following TLR ligands: lipopolysaccharide (TLR4), Pam3CSK4 (TLR1/2), flagellin (TLR5), zymosan (TLR2), polyinosinic:polycytidylic acid (TLR3), imiquimod (TLR7), and CpG (TLR9). Interleukin (IL)-8, IL-6, tumor necrosis factor, IL-1β, and IL-10 concentrations were analyzed in culture supernatants., Results: Compared with the effects in adult blood, lipopolysaccharide-, Pam3CSK4-, flagellin-, and polyinosinic:polycytidylic acid-stimulated inflammatory cytokine production in cord blood was generally weak in monocytes, comparable in DCs, and elevated in MoDCs. CpG- and imiquimod-stimulated cytokine production in DCs was comparable in cord blood and adult blood, but cytokine production was almost absent in monocytes and MoDCs in both cord blood and adult blood. In contrast, zymosan stimulation produced comparable inflammatory cytokine profiles in the monocytes, DCs, and MoDCs of cord blood and adult blood., Conclusion: The immaturity of TLR-mediated innate immunity in neonates depends on monocytes rather than on DCs. Our results indicate that zymosan-mediated TLR2 signaling may be useful for developing a neonatal vaccine adjuvant., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: We aimed to construct reference ranges for time intervals of each component of cardiac flow velocity waveforms in normal fetuses, comparing those variables between right and left ventricles., Methods: In 359 fetuses at the gestational age of 17-38 weeks, the durations of atrioventricular (AV) valve opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A) waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E-wave, dec-A for A-wave, and dec-ET for ejection time) were studied cross sectionally., Results: Both right and left acc-E showed the strongest correlations with gestational age (r = 0.478 and r = 0.519, respectively). Left AVVO showed a stronger correlation (r = 0.474) than right AVVO (r = 0.282) and, conversely, right AVVC showed a stronger correlation (r = 0.399) than left AVVC (r = 0.195) with gestational age. Significant differences (all P values <0.001) were observed for all right and left parameters other than total-A and acc-E., Conclusions: Characteristic differences between right and left ventricles were found in the reference ranges, suggesting the developmental properties of the fetal heart. © 2014 John Wiley & Sons, Ltd., (© 2014 John Wiley & Sons, Ltd.)

The Urogynecology Committee of the Asia and Oceania Federation of Obstetrics and Gynaecology (AOFOG) has held seminars and workshops on various urogynecological problems in each country in the Asia-Oceania area in order to encourage young obstetricians and gynecologists. In 2013, we organized the operative seminar for obstetrical anal sphincter injuries (OASIS) in which we prepared porcine models to educate young physicians in a hands-on workshop at the 23rd Asian and Oceanic Congress of Obstetrics and Gynaecology in Bangkok, Thailand. Laceration of the anal sphincter mostly occurs during vaginal delivery and it can develop into anal sphincter deficiency, which causes fecal incontinence, if an appropriate suture is not performed. OASIS has become an important issue, especially in developing countries. The prevalence of OASIS of more than the third degree is around 5% in primary parous women and the frequency is higher when detected by ultrasonographic evaluation. Several risk factors, such as macrosomia, instrumental labor, perineal episiotomy and high maternal age, have been recognized. In a society where pregnant women are getting older, OASIS is becoming a more serious issue. An intrapartum primary appropriate stitch is important, but the 1-year outcome of a delayed operation after 2 weeks postpartum is similar. A randomized controlled study showed that overlapping suture of the external sphincter is better than that of end-to-end surgical repair. The Urogynecology Committee of the AOFOG would like to continue with educative programs about the appropriate therapy for OASIS., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor β, showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower β-tubulin levels and comparatively higher p53/β-tubulin or CAR /β-tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells.

Objective: To evaluate the clinical outcomes of traditional surgical approaches to pelvic organ prolapse., Methods: From January 20, 2000, to March 24, 2009, 182 patients underwent traditional prolapse surgery at Osaka City University Graduate School of Medicine, Osaka, Japan, after prolapse assessment by the pelvic organ prolapse quantification system. Incontinence, defined as more than 2 g of urine leaked in a 1-hour pad test; posterior urethrovesical angle, using chain cystography; and quality of life (QOL), using a face visual analog scale, were assessed 1, 3, 6, and 12 months postoperatively, and then annually for 2 more years, in the 167 patients who completed follow-up. The presence of lower urinary tract symptoms was determined preoperatively and postoperatively., Results: The anatomic and subjective recurrence rates were 21.0% and 6.0%. There was a significant difference in time to recurrence between anatomic and subjective prolapse. The posterior urethrovesical angle was improved postoperatively. The prevalence of lower urinary tract symptoms was 67.1% preoperatively and decreased to 28.2%, 17.2%, 16.2%, 15.6%, and 15.6% at 1 month, 6 months, 1 year, 2 years, and 3 years, respectively, and QOL was improved postoperatively regardless of anatomic recurrence., Conclusion: Anatomic support and QOL were satisfactory after traditional prolapse surgery., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objectives: To investigate time intervals of ductus venosus (DV) flow velocity waveforms (FVW) in correlation to fetal heart rate and gestational age and to construct reference ranges for the second and third trimester. Furthermore, we investigate time intervals of FVW through the tricuspid valve., Methods: Flow velocity waveforms of the DV and through the tricuspid valve were recorded in 135 normal singleton fetuses between 17 and 38 weeks' gestation. Time intervals for systolic (S) and early diastolic (D) peaks were analyzed regarding acceleration time (acc-S for S, acc-D for D) and deceleration time (dec-S for S, dec-D for D), respectively. Similarly, time intervals for both peaks of right ventricular inflow were analyzed regarding acceleration time (acc-E for E-wave, acc-A for A-wave) and deceleration time (dec-E for E-wave, dec-A for A-wave), respectively., Results: In the DV, acc-D and dec-D increased significantly with gestational age. In tricuspid valve, acc-E and acc-A showed a significant increase with gestational age. All parameters except acc-S showed significant negative correlations with fetal heart rate., Conclusion: With advancing gestational age, prolongation of the diastolic phase of DV-FVW and of the E-wave of tricuspid flow was observed, suggesting maturation of ventricular diastolic function. Time-related analysis of Doppler signals of DV-FVW may provide detailed insights into fetal cardiac function., (© 2012 John Wiley & Sons, Ltd.)

Aim: The connective tissue located between the uterine cervix and sacrospinous ligament (the uterospinous connective tissue; USCT) has recently been noted as the level 1 supportive tissue instead of the classical uterosacral ligament. We examined whether or not the USCT changes its histological architecture by vaginal delivery in correlation with the levels 2 and 3 supportive tissues., Methods: In the pelvic floors of 17 female cadavers (9 nuliparous and 8 multiparous), we compared histological architectures among the USCT, arcus tendineus fasciae pelvis (ATFP) and perineal membrane (PM)., Results: The USCT was evident as a string-like tissue structure in multiparous women or a thick mesh in nuliparous women. It consistently contained fewer elastic and smooth muscle fibers than other levels. In contrast, the ATFP usually contained abundant elastic fibers and smooth muscle. Likewise, the PM also displayed a constant morphology., Conclusion: Although all three sites were likely to be injured by delivery, the USCT seemed to be more severely damaged and/or more difficult to be recovered than the ATFP and PM., (© 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.)

A 64-year-old woman presented with severe infection accompanied by iliosacral arthritis and retroperitoneal abscess after tension-free vaginal mesh reconstruction using polypropylene meshes (GyneMesh; Gynecare, Ethicon, Somerville, NJ, USA) for pelvic organ prolapsed quantification of stage 3 pelvic organ prolapse. Three weeks after the operation, she complained of high fever (39 degrees C) and sharp pain from the left buttock down to the left lower limb. Computed tomography revealed a retroperitoneal abscess and osteolysis caused by iliosacral arthritis. Because the infection was not resolved by drainage and antibiotic therapy, the left portion of the mesh was removed. She recovered after mesh removal, and no recurrent abscess was observed in the CT after a 6-month follow-up. However, the patient complained of sporadic discomfort in the left buttock, and a blood examination performed during this period, revealed a slight elevation in the C-reactive protein level. Although this symptom was resolved by oral antibiotics, further follow-up was required.

The aims of this study were, using fixed and fresh cadavers, to clarify how closely the pelvic splanchnic nerve, levator ani nerve (LAN), and sacrospinous ligament (SSL) are located and to examine how to avoid nerve injury during the posterior tension-free vaginal mesh procedure (TVMP), in which mesh is applied through the SSL. Macroscopic dissection of fixed cadavers demonstrated that the LAN crossed the inside of the SSL at a point 0-18 mm medial to the ischial spine and entered the muscle at a point 12-26 mm inferior to the ischial spine and 40-55 mm anterolateral to the coccyx. Dissection after TVMP of fresh cadavers revealed that the point of penetration of mesh through the SSL was close to the LAN. To preserve the LAN, penetration of the SSL should be within 5 mm of the lower margin at a point 20-25 mm medial to the ischial spine.

Female perineal structures located around the perineal body were histologically examined using semiserial sections obtained from 15 elderly female cadavers. The smooth muscle content of the perineal body was greater in multiparous women. The connective tissue of the perineal body extended inferolaterally and provided a fibromuscular mass that was 10-30 mm long mediolaterally and 3-15 mm long superoinferiorly. The lateral extension (LEX) of the perineal body occupies a space that is surrounded by the vestibular bulb, internal anal sphincter, and levator ani slings. The LEX did not directly connect to the ischiopubic bony rami but did connect indirectly via the vestibular bulb and ischiocavernosus. Thus, the LEX appears to play a critical role for maintaining the topographical relationship between the vagina and the rectum. The surgical approximation of bilateral LEX instead of levator ani may be of key importance when doing a perineorrhaphy. As pudendal nerve branches run along the inferior margin of the LEX, a mediolateral episiotomy may not be the best option.

Glucose transporter-1 (GLUT1), one of the key functional indicators of placental differentiation, has an important role in placental glucose transport. We previously showed that the protein levels of GLUT1 and nuclear transcription factor specificity protein-1 (Sp1) in rat choriocarcinoma cells (Rcho-1 cells) decreased during the differentiation of these cells to giant cells. We also showed that Sp1 was involved in the regulation of GLUT1 gene expression during this process. RelA-associated inhibitor (RAI) is an inhibitor of nuclear factor-kappaB that was identified by a yeast two-hybrid screen and is preferably expressed in human placenta and heart. RAI was also found to interact with Sp1 and exert an inhibitory effect against the DNA-binding activity of Sp1. We first show here that RAI mRNA expression increased as gestation proceeded and that RAI was localized mainly in the syncytiotrophoblast throughout pregnancy. The chloramphenicol acetyltransferase activity assay in Rcho-1 cells revealed that cotransfection of RAI expression vector resulted in decreased activity of the rat GLUT1 promoter but not in that of a mutated rat GLUT1 promoter lacking the Sp1 binding site. Furthermore, the protein level of RAI increased during differentiation. In addition, transfection of RAI expression vector promoted the morphological differentiation of Rcho-1 cells, and RAI knockdown using RAI-specific small interfering RNA reveals inhibitory effects on the morphological differentiation, as assessed by photomicroscopy. Taken together, these findings suggest that RAI may be involved in the regulation of trophoblast differentiation via interaction with Sp1.

To get support from morphological findings to develop a novel surgical procedure for posterior vaginal defect repair, we histologically examined the rectum-vagina interface tissues obtained from 20 elderly female cadavers. The rectovaginal septum (RVS) was defined here as an elastic fiber-rich plate (EFRP) along the posterior vaginal wall. It lined the posterior surface of the vein-rich zone of the vaginal wall and extended between the bilateral paracolpiums. The septum was more evident in the lower half of the interface than in the upper half. The RVS was often thin and interrupted. Since the RVS was not so clearly demonstrated in the upper vagina histologically, augmentation using some implant is considered to be necessary for the enterocele and high rectocele. Since the thickness and tightness of the RVS vary with the case in the lower vagina, surgical procedures for low rectocele repair should be individualized, including implant-augmentation.

Up- and down-regulation of various genes in the placenta, decidua and amnion has been reported during the mid-late period of pregnancy and in pregnancy-related complications, such as preeclampsia and preterm labor. However, whether this gene regulation at the feto-maternal interface directly influences the physiology/pathophysiology of disease remains unknown. In order to study this problem, transient gene transfer into the pregnant uterus at mid-late term would be a useful tool. We injected exogenous plasmid entrapped using a commercially available Hemagglutinating Virus of Japan Envelope (HVJ-E) vector system (GenomONE Neo, Ishihara Sangyo) into the extra-amniotic space of the upper part of the pregnant mouse uterus on day 14.5 post-coitus (p.c.). Luciferase activity driven by the cytomegalovirus promoter was detectable for 3 days after transfection in the upper, middle and lower part of the uterus. beta-Galactsidase activity was localized in the basal lamina of the placenta, the decidual membrane and the fetal membrane. Exogenous plasmid was not transmitted to the fetus. The course of pregnancy was not disturbed by this procedure; rupture of membranes, intrauterine fetal growth restriction and preterm birth were not observed. Thus, we demonstrated that this transient gene transfer method is highly efficient and minimally invasive, and expect that this procedure will be a useful tool to analyze the pathophysiology of pregnancy-related disorders.

Objective: Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. The aim of the present study was to examine whether there is an association between the SLPI concentration in the cervicovaginal secretion (CS) and vaginal complaints of post-menopausal women., Methods: Uterine cervix tissues and CS of peri- or post-menopausal women were obtained. SLPI was assayed by ELISA. To determine the level of SLPI mRNA and the localization of SLPI protein in the uterine cervix, we performed RT-PCR and immunochemical staining, respectively., Results: The levels of SLPI in the CS of post-menopausal women with vaginal complaints were significantly lower that those of post-menopausal women without vaginal complaints. The levels of SLPI in the CS of post-menopausal women were lower that those of peri-menopausal women and post-menopausal women treated with hormone replacement therapy. Positive staining was observed in epithelial cells of the cervix of elderly women, however, the intensity was weaker than that in peri-menopausal women. Positive staining was also observed in gland cells of the cervix of peri-menopausal women, but not in those of post-menopausal women. SLPI transcripts were detected in the cervix of post-menopausal women. The treatment of post-menopausal women with vaginal estrogen increased the concentrations of SLPI in CS of post-menopausal women., Conclusions: The present findings suggest that the decreased amount of SLPI in the CS of post-menopausal women might be one of the causes of the symptoms of post-menopausal women and contribute to the immunodefense mechanisms of the elderly women.

Choroid plexus cysts (CPC) are a well-known ultrasound aneuploidy marker easily detectable at second-trimester ultrasound examination. However, their genetic etiology is totally unknown. We report two cases of Japanese mothers who carried two and three siblings respectively; all the fetuses that had CPC were noticed at second trimester. Genetic amniocentesis revealed that each fetus had different karyotypes, that is, trisomy 18 and 46,XX in the case of one mother, and trisomy 18, 46,XY and trisomy 21 in the case of the other. These observations indicate that the genetic basis of the cysts is not linked to abnormal chromosomes. We propose that careful ultrasound observation and genetic counseling of the siblings should be offered to patients who have previously had a baby with CPC, despite that baby having a normal karyotype.

In vivo transient transfection of cDNA into uterine endometrium during the implantation period provides great opportunities to analyse the physiology/pathophysiology of implantation at the molecular level. We review here methodologies which have been applied for this purpose. Viral vectors are widely used for in vivo gene therapy models; however, there is no successful example of gene transfer into the uterus using such vectors. Cationic liposome-based technologies have produced some successful results, causing alterations in implantation physiology. We applied a haemagglutinating virus of Japan envelope (HVJ-E) vector system and showed that the transfection efficiency was much higher than that of methods based on cationic liposome. Commercial HVJ-E vector (GenomONE-Neo) is now also available. Several successful examples of in vivo gene transfer revealed that calcitonin, Hoxa 10 and NF kappaB play important roles in determining the efficiency or timing of implantation. Based on this knowledge, we should further analyse the pathophysiology of human implantation failure using human materials.

Aim: Stress urinary incontinence (SUI) is accompanied by pelvic organ prolapse (POP) in many cases. We investigate a procedure to adjust the level of suspension of the mid-urethra using tension-free vaginal tape (TVT) under general anesthesia at the time of POP repair surgery., Methods: Preliminary examination carried out prior to this study showed that the pressure stress applied by a surgeon is less than half of that induced using the cough-stress method: the manual-tapping method (MTM) showed an average intravesical urinary leak point pressure (IULPP) of 21.4 mmHg (range 19-23 mmHg), when the cough-stress method demonstrated an average IULPP >52.4 mmHg (range 45-58 mmHg; n = 3). An attempt was made to predict postoperative SUI by packing sponge gauze into the manually replaced vagina preoperatively. If SUI appeared, TVT was added to the repair operation for POP in those patients (n = 11). Lastly, the MTM was used to decide the level of urethral suspension during the TVT procedure following POP repair surgery under general anesthesia (n = 11)., Results: Eleven patients underwent the TVT procedure combined with POP repair surgery. The mean postoperative follow-up period was 23.8 months (range 9-40 months). There was no case of post-surgical ischuria. One patient showed a cystocele during the postoperative course. However, all other patients were relieved from the symptoms of POP, and none complained of SUI following the procedure., Conclusion: The MTM seems to be a more appropriate indicator by which to adjust the level of urethral suspension during the TVT procedure than the conventional method, particularly under general anesthesia. To prevent and cure perioperative SUI, the MTM as a TVT procedure combined with POP repair surgery under general anesthesia is a useful procedure.

To reinforce the support of the vagina, concurrent use of iliococcygeus fascia colpopexy with the McCall culdeplasty was scheduled for primary uterine prolapse. Forty-five women with primary uterine prolapse without stress urinary incontinence were treated by McCall culdeplasty alone or McCall culdeplasty plus iliococcygeus fascia colpopexy for suspension of the upper portion of the vagina. Recurrence of vaginal support defects were carefully followed for 15-50 months. Additional iliococcygeus fascia colpopexy did not change with the axis of the vagina obtained by McCall culdeplasty, although it prolonged total operation time by 32 min and increased blood loss by 94 ml. Two cases (8.3%) had postoperative vaginal defects in the group undergoing combined procedures and seven recurrent cases (33.3%) were observed in the group undergoing McCall culdeplasty alone. The durability of the combined procedures was superior to that of the modified McCall culdeplasty alone by Kaplan-Meier analysis. These results suggest that iliococcygeus fascia colpopexy is reasonably safe and strengthens not only the attachment of the upper part of the vagina but also that of the anterolateral vaginal wall.

Problem: Various kinds of contraction-associated molecules are up-regulated at the initiation of labor. However, expression profiling has revealed that many molecules are also down-regulated. The effect of down-regulation of molecules by protein degradation on parturition is not known., Methods of Study: We administered lactacystin, a specific proteasome inhibitor, to mouse preterm birth model induced by antiprogesterone RU486 on day 16.0 post-coitus. NF-kappaB activity, and the levels of transcripts for oxytocin receptor, prostaglandin F(2alpha) receptor (FP), cyclooxygenase-1, -2, and interleukin-1beta in the uterus were examined by electrophoretic mobility shift assay and semi-quantitative reverse transcriptase-polymerase chain reaction, respectively., Results: Administration of lactacystin significantly prolonged the time until the delivery of the first pup. FP mRNA level was solely elevated by RU486 treatment, and lactacystin significantly suppressed this up-regulation., Conclusions: Proteolysis by proteasomes in the uterus regulates the initiation of labor, at least in part, via control of contraction-associated molecules such as FP.

Nuclear factor kappaB (NF-kappaB) is activated in the murine endometrium during implantation period [Am. J. Reprod. Immunol. 51 (2004) 16]. Transient transfection of IkappaBalpha mutant (IkappaBalphaM) cDNA into the mouse uterine cavity using hemagglutinating virus of Japan envelope vector suppressed uterine NF-kappaB activity less than half of that observed in control on days 3.5 and 4.5 p.c. IkappaBalphaM cDNA transfection led to significant delay of implantation. After IkappaBalphaM cDNA transfection, LIF mRNA expression in the uterus was significantly suppressed on days 3.5 and 4.5 p.c. Co-transfection of LIF cDNA with IkappaBalphaM cDNA in the uterus partially rescued the delay of implantation induced by suppression of NF-kappaB activity. Taken together, these findings indicate that NF-kappaB activation determines the timing of the implantation, at least in part, via control of LIF expression.

Chorioamnionitis (CAM) is one of the causes of preterm labour. A recent study has indicated that NADPH oxidase, a reactive oxygen species (ROS)-producing enzyme, is activated in CAM. CAM is thought to be closely associated with oxidative stress. We have hypothesized that oxidative stress in CAM may induce preterm labour. The purpose of this study is to examine the effect of 4-hydroxy-2-nonenal (HNE), which is a marker of oxidative stress, on human placenta during preterm labour. We initially examined the HNE-modified proteins in human placentas by immunoblotting and immunohistochemistry using anti-HNE antibody. To examine the effect of HNE on human placenta, we stimulated human placental tissue with HNE. The expressions of cyclooxygenase-2 (COX-2) mRNA and protein were observed by RT-PCR and western blot analysis respectively. Furthermore, we measured the peroxidase activity of COX-2 by COX activity assay kit. Prostaglandin E(2) (PGE(2)) in the supernatants of placental tissue was also determined by enzyme-linked immunosorbent assay. Immunoblotting and immunohistochemistry showed that the levels of HNE-modified proteins were increased in the placentas with CAM, compared to the normal placenta. HNE induced the expression of COX-2 mRNA, protein and activity in the placental tissue culture stimulated with HNE. In addition, PGE(2) was also released into the medium in a time-dependent fashion. These findings suggest that HNE-modified proteins, which were increased in the placenta with CAM, play an important role in preterm labour.

Problem: This study was aimed to isolate cDNAs for genes whose expression levels are dynamically regulated at the feto-maternal interface around parturition., Method: The suppression subtractive hybridization (SSH) method was used to compare the gene expression patterns of human choriodecidual membranes from term elective Caesarian delivery before labor (BL) and term vaginal delivery (VD). Northern blotting, quantitative real-time RT-PCR and in situ hybridization were performed to determine temporal and spatial expression of candidate clones., Result: After SSH procedure, we selected decorin from the cDNA library of BL for further investigation. The mean level of decorin transcription tended to be higher in BL samples than in VD or preterm samples. Decorin mRNA was mainly expressed in the decidual cells. Decorin gene expression was also upregulated in the term myometrium., Conclusion: These results suggest that dynamically increased expression of decorin in the choriodecidual membrane during parturition may be a part of the uterine preparation for labor.

Aim: Prostaglandin D (PGD), synthesized by lipocalin-type prostaglandin D synthase (L-PGDS), has marked effects on a number of biological processes, including the prevention of platelet aggregation and the relaxation of vascular smooth muscle. The aim of the study presented here was to examine the significance of L-PGDS in human pregnancy., Methods: We measured the concentration of plasma L-PGDS in pregnant and non-pregnant women, and the concentration of L-PGDS in the umbilical cord blood, amniotic fluid and urine of newborns by enzyme-linked immunoabsorbent assay. To determine the localization of L-PGDS, we performed immunohistochemical analysis. To evaluate the usefulness of diagnosis of rupture of membranes (ROM), we determined the concentration of L-PGDS in cervicovaginal secretions., Results: Pregnant women and non-pregnant women had similar L-PGDS concentrations (0.57 +/- 0.13 microg/mL vs 0.53 +/- 0.07 microg/mL). Umbilical cord blood, amniotic fluid and newborn urine contained higher L-PGDS concentrations (1.87 +/- 0.73 microg/mL, 2.62 +/- 0.86 microg/mL, 6.31 +/- 4.62 microg/mL, respectively) than maternal blood. The concentration of L-PGDS in amniotic fluid from 19 weeks onward was significantly greater than that at 15-18 weeks (3.201 +/- 0.384 microg/mL, n = 6 vs 1.735 +/- 0.477 microg/mL, n = 4; P < 0.05). Immunohistochemistry revealed that the amniotic cells of the placenta expressed L-PGDS. The sources of L-PGDS in amniotic fluid are fetus urine and amniotic cells. The concentration of L-PGDS in cervicovaginal secretions with rupture of membrane (ROM) were significantly higher than those without ROM., Conclusion: The measurement of L-PGDS in cervicovaginal fluid was useful in the detection of ROM during pregnancy.

Problem: Nuclear factor kappa B (NF-kappaB) 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-kappaB at implantation window is unknown., Methods: Activation of NF-kappaB in the mouse uterus was determined by electrophoretic mobility shift assays. Localization of p50 and p65, components of NF-kappaB, was analyzed by immunohistochemistry., Results: NF-kappaB was activated in the proestrus and estrus phases in non-pregnant uterus. In the pregnant uterus, NF-kappaB was activated after day 1.5 post-coitum, and the activation continued during implantation period. The immunoreactivities of p50 and p65 were mainly localized in endometrial epithelium, and were weaker in endometrial stroma cells., Conclusion: NF-kappaB activity is dynamically regulated during the sexual cycle as well as during the implantation period in the endometrium, where the biochemical interaction between mother and conceptus first occurs.

Objective: To investigate the incidence of embryonic/fetal pleural effusion in the first trimester and its pregnancy outcome., Methods: A total of 965 viable singleton pregnancies confirmed by sonography between 7 and 10 weeks were examined to estimate the incidence of embryonic/fetal pleural effusion. When initial transvaginal sonography showed pleural effusion, serial ultrasound examinations were performed., Results: Pleural effusion was detected in 12 pregnancies (incidence, 1.2%; 95% confidence interval, 0.7-2.2), which involved bilateral thoracic cavities in all cases. The pregnancy outcome was assessed among 14 cases of pleural effusion, including 2 previously reported cases from the same institution. Among these, 12 pregnancies (86%) miscarried by 14 weeks' gestation. Karyotype was abnormal in 9 (82%) of 11 cases in which chromosomal analysis was successfully performed. Of these, 6 (67%) were 45,X., Conclusions: The results suggested that embryonic/fetal pleural effusion in early pregnancy was associated with poor pregnancy outcome such as spontaneous abortion and chromosomal abnormality.

Objective: To evaluate (1) the diagnostic usefulness of oncofetal fibronectin (fFN) in the cervical fluid in unruptured ectopic pregnancy, and (2) the contribution of maternal blood contamination of the specimen to the test results., Study Design: A total of 111 cases in the first trimester of pregnancy, including 12 cases of ectopic pregnancy, 26 of spontaneous abortion and 73 of viable intrauterine pregnancy, were studied. fFN was determined with a commercial enzyme-linked immunosorbent assay kit with a threshold of 50 ng/mL in cervical fluid. To determine the effect of blood contamination on the fFN assay, the positive rate of the fFN test was examined when maternal blood in the first trimester was mixed with the dilution buffer., Results: Eighty-three percent (10/12), 38% (10/26) and 12% (9/73) of cases with ectopic pregnancy, miscarriage and normal pregnancy, respectively, were positive for fFN. The positive rate in ectopic pregnancy was significantly higher than in normal pregnancy and spontaneous abortion. The test was positive for fFN in 8% with 0.5% of blood contamination, 67% with 1% contamination and 100% with 10% contamination.