Details of a Researcher - Tanaka, Mamoru

Papers - Tanaka, Mamoru

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Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus

Kasuga Y., Miyakoshi K., Tajima A., Saisho Y., Ikenoue S., Ochiai D., Matsumoto T., Arata N., Hata K., Tanaka M.

Journal of Diabetes Investigation (Journal of Diabetes Investigation) 10 ( 3 ) 817 - 826 2019.05

ISSN 20401116

© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd Aims/Introduction: Risk factors of type 2 diabetes mellitus in Japanese women with recent gestational diabetes mellitus are unknown. The objective of the present study was to investigate the clinical and genetic characteristics associated with postpartum abnormal glucose tolerance in Japanese women with gestational diabetes mellitus. Materials and Methods: A total of 213 Japanese women with recent gestational diabetes mellitus who underwent a postpartum 2-h oral glucose tolerance test were investigated. The association between antepartum clinical characteristics and postpartum abnormal glucose tolerance (diabetes or prediabetes based on the Japan Diabetes Society criteria) was examined. Frequencies of 45 known type 2 diabetes mellitus-associated genetic variants were also compared between women with and without postpartum abnormal glucose tolerance. Results: A total of 59 women showed postpartum abnormal glucose tolerance (prediabetes, n = 51; diabetes, n = 8). Plasma glucose levels at 1 or 2 h, the insulinogenic index and the insulin secretion-sensitivity index-2 of the antepartum oral glucose tolerance test were independent of postpartum abnormal glucose tolerance risk factors (P = 0.006, P = 0.00002, P = 0.01 and P = 0.006, respectively). Four genetic variants (rs266729 [ADIPOQ], rs6017317 [HNF4A], rs5215 [KCNJ11] and rs7177055 [HMG20A]) showed a nominally significant association with postpartum abnormal glucose tolerance (P < 0.05, respectively). Among these, three were related to insulin secretion. Postpartum abnormal glucose tolerance risk significantly increased with increasing risk-allele number (P = 0.0005; odds ratio 1.91). Conclusions: Clinical features and genetic variants related to impaired insulin secretion are risk factors of postpartum abnormal glucose tolerance in Japanese women with recent gestational diabetes mellitus.

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Safe and easy technique for the laparoscopic application of Seprafilm® in gynecologic surgery

Ota K., Sato K., Ogasawara J., Takahashi T., Mizunuma H., Tanaka M.

Asian journal of endoscopic surgery (Asian journal of endoscopic surgery) 12 ( 2 ) 242 - 245 2019.04

© 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd. INTRODUCTION: Laparoscopic surgery is a minimally invasive surgery, and the rate of postoperative adhesions is low. Although Seprafilm® helps to reduce adhesions, its application in the abdominal cavity during laparoscopic surgery is difficult because of its material. Therefore, we propose an easy method for applying this adhesion barrier. MATERIALS AND SURGICAL TECHNIQUE: The Seprafilm is cut into four equal pieces. The four pieces are stacked, firmly folded twice, and grasped with the forceps. The reducer sleeve is slid over the bundle of Seprafilm. The forceps with the reducer sleeve is inserted through a 12-mm trocar near the target area. The reducer sleeve is then slid down the forceps to uncover the Seprafilm. Finally, each piece of Seprafilm is applied over the suture area. In all cases, the Seprafilm was successfully applied to the intended target. There were no cases in which Seprafilm was incompletely applied or in which it could not be used because of moistening. The average application times of surgeon 1 and surgeon 2 were 4.8 min and 5.0 min, respectively; this difference was not significant. There were no postoperative complications in any case. DISCUSSION: It is safe and easy to use our simple technique to apply Seprafilm adhesion barrier laparoscopically. Further studies are warranted to prove Seprafilm's efficacy after such application.

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Distinctive subpopulations of the intestinal microbiota are present in women with unexplained chronic anovulation

Sasaki H., Kawamura K., Kawamura T., Odamaki T., Katsumata N., Xiao J.Z., Suzuki N., Tanaka M.

Reproductive BioMedicine Online (Reproductive BioMedicine Online) 38 ( 4 ) 570 - 578 2019.04

ISSN 14726483

© 2018 The Authors Research question: Do gut microbiota associate with the ovulatory cycle in women showing normogonadotrophic anovulation? In humans, the gut microbiota affects diverse physiological functions and dysbiosis (microbial imbalance) may lead to pathological syndromes. However, there is comparatively little information on the relevance of gut microbiota to reproductive functions in women. Here, a group of women with idiopathic chronic anovulation were examined, who do not exhibit any apparent endocrinological disorder, as they are suitable for investigating the relationship between intestinal bacteria and ovulatory disorders. Design: A prospective observational cohort study was performed on two groups of women who did not exhibit apparent endocrinological disorders but showed either irregular menstrual cycles (IMC group) or normal menstrual cycles (controls). The bacterial composition of faeces from rectal swabs from the women was analysed using next-generation sequencing based on bacterial 16SrRNA genes. Results: A metagenomic analysis indicated that the two groups of women had significant differences in 28 bacterial taxa in their faeces. Prevotella-enriched microbiomes were more abundant in the IMC group, whereas Clostridiales, Ruminococcus and Lachnospiraceae (butyrate-producing bacteria) were present at lower levels in the IMC group. Conclusions: Distinctive subpopulations of intestinal microbiota were identified in women with unexplained chronic anovulation. The results indicate that gut microbiota could be associated with ovarian functions.

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National survey of uterine rupture in Japan: Annual report of Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2018

Makino S., Takeda S., Kondoh E., Kawai K., Takeda J., Matsubara S., Itakura A., Sago H., Tanigaki S., Tanaka M., Ikeda T., Kanayama N.

Journal of Obstetrics and Gynaecology Research (Journal of Obstetrics and Gynaecology Research) 45 ( 4 ) 763 - 765 2019.04

ISSN 13418076

© 2019 Japan Society of Obstetrics and Gynecology Aim: To clarify the frequency of occurrence of uterine rupture and its prognosis, a nationwide survey was performed. Methods: Cases of uterine rupture recorded for a period of 5 years were included. Results: There were 152 cases of uterine rupture with an incidence rate of 0.015%. The scarred uterine rupture cases were found to have a significantly earlier occurrence of uterine ruptures in comparison to the unscarred cases: unscarred 39.0 weeks, cesarean section 37.0 weeks, myomectomy 32 weeks and adenomyomectomy 30–32 weeks. And it became apparent that the frequency of hysterectomy, cerebral palsy and neonatal death were higher in the cases of uterine rupture during labor than before delivery. Among the cases of scarred uterine rupture, neonatal prognosis was poorer in cases of pregnancy after myomectomy or adenomyomectomy in comparison with postcesarean section cases. Conclusion: This survey revealed the current incidence of uterine rupture in Japan.

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Membrane protein CD9 is repositioned and released to enhance uterine function

Iwai M., Hamatani T., Nakamura A., Kawano N., Kanai S., Kang W., Yoshii N., Odawara Y., Yamada M., Miyamoto Y., Saito T., Saito H., Miyado M., Umezawa A., Miyado K., Tanaka M.

Laboratory Investigation (Laboratory Investigation) 99 ( 2 ) 200 - 209 2019.02

ISSN 00236837

© 2018, United States & Canadian Academy of Pathology. Tetraspanin CD9 is essential for sperm–egg fusion and also contributes to uterine repair through microexosome formation. Microexosomes share CD9 with exosomes and are released from eggs and uterine epithelial cells. However, the mechanism for the formation of microexosomes remains unknown. To address this issue, we examined membrane localization and extracellular release of CD9 proteins using uterine epithelial cells and secretions in mice and humans. In mice, CD9 localized predominantly on the basal region of the plasma membrane and relocated to the apical region upon embryo implantation. Furthermore, extracellular CD9 proteins were detected in uterine secretions of mice and women undergoing infertility treatment, but were below detectable levels in supernatants of pluripotent stem cells. Ultrastructural analysis demonstrated that membrane projections were shortened and the number of mitochondria was reduced in uterine epithelial cells lacking Cd9 genes. Our results suggest that CD9 repositioning and release affect both membrane structures and mitochondrial state in the uterus, and contribute to female fertility.

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Human amniotic fluid stem cells have a unique potential to accelerate cutaneous wound healing with reduced fibrotic scarring like a fetus

Fukutake M., Ochiai D., Masuda H., Abe Y., Sato Y., Otani T., Sakai S., Aramaki-Hattori N., Shimoda M., Matsumoto T., Miyakoshi K., Kanai Y., Kishi K., Tanaka M.

Human Cell (Human Cell) 32 ( 1 ) 51 - 63 2019.01

ISSN 09147470

© 2018, Japan Human Cell Society and Springer Japan KK, part of Springer Nature. Adult wound healing can result in fibrotic scarring (FS) characterized by excess expression of myofibroblasts and increased type I/type III collagen expression. In contrast, fetal wound healing results in complete regeneration without FS, and the mechanism remains unclear. Amniotic fluid cells could contribute to scar-free wound healing, but the effects of human amniotic fluid cells are not well characterized. Here, we determined the effect of human amniotic fluid stem cells (hAFS) on FS during wound healing. Human amniotic fluid was obtained by amniocentesis at 15–17 weeks of gestation. CD117-positive cells were isolated and defined as hAFS. hAFS (1 × 10 6 ) suspended in PBS or cell-free PBS were injected around wounds created in the dorsal region of BALB/c mice. Wound size was macroscopically measured, and re-epithelialization in the epidermis, granulation tissue area in the dermis and collagen contents in the regenerated wound were histologically analyzed. The ability of hAFS to engraft in the wound was assessed by tracking hAFS labeled with PKH-26. hAFS fulfilled the minimal criteria for mesenchymal stem cells. hAFS injection into the wound accelerated wound closure via enhancement of re-epithelialization with less FS. The process was characterized by lower numbers of myofibroblasts and higher expression of type III collagen. Finally, transplanted hAFS were clearly observed in the dermis until day 7 implying that hAFS worked in a paracrine manner. hAFS can function in a paracrine manner to accelerate cutaneous wound healing, producing less FS, a process resembling fetal wound healing.

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The neurorestorative effect of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic–ischemic encephalopathy in mice

Otani T., Ochiai D., Masuda H., Abe Y., Fukutake M., Matsumoto T., Miyakoshi K., Tanaka M.

Pediatric Research (Pediatric Research) 85 ( 1 ) 97 - 104 2019.01

ISSN 00313998

© 2018, International Pediatric Research Foundation, Inc. Background: Hypoxic–ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE. Methods: hAFS were isolated from AF cells as CD117-positive cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or phosphate‐buffered saline at 10 days post HI and were harvested for histological analysis after functional tests at 21 days post HI. We also implanted PKH26-positive hAFS to assess their migration to the brain. Finally, we determined gene expressions of trophic factors in hAFS co-cultured with HI brain extract. Results: hAFS improved sensorimotor deficits in HIE by gray and white matter restoration and neuroinflammation reduction followed by migration to the lesion. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions in hAFS were elevated when exposed to HI-induced brain extract. Conclusion: hAFS induced functional recovery by exerting neurorestorative effects in HIE mice, suggesting that intranasal administration of hAFS could be a novel treatment for HIE, especially in the chronic phase.

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Chemotactic behavior of egg mitochondria in response to sperm fusion in mice

Iwai M., Harada Y., Miyabayashi R., Kang W., Nakamura A., Kawano N., Miyamoto Y., Yamada M., Hamatani T., Miyado M., Yoshida K., Saito H., Tanaka M., Umezawa A., Miyado K.

Heliyon (Heliyon) 4 ( 11 ) 2018.11

ISSN 24058440

© 2018 The Authors Mitochondria are the powerhouses of eukaryotic cells and their positioning contributes to fertilization and early developmental processes. We report that sperm fusion triggers Ca2+ oscillations and mitochondrial movement toward fused sperm (mitochondrial chemotaxis) in mouse eggs. Mitochondria functioned in Ca2+ storage and were colocalized with endoplasmic reticulum (ER) during Ca2+ oscillations. Mitochondria then moved toward the fused sperm. Sperm extracts lacking nuclei induced Ca2+ oscillations, but did not promote mitochondrial chemotaxis. Our results suggest that sperm fusion motivates Ca2+ oscillation-independent mitochondrial chemotaxis. This phenomenon indicates that egg mitochondria interact with sperm materials, presumably nuclear substances, and their network tethers egg and sperm nuclei at the early stage of zygote formation.

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Degradation of phosphate polymer polyP enhances lactic fermentation in mice

Nakamura A., Kawano N., Motomura K., Kuroda A., Sekiguchi K., Miyado M., Kang W., Miyamoto Y., Hanai M., Iwai M., Yamada M., Hamatani T., Saito T., Saito H., Tanaka M., Umezawa A., Miyado K.

Genes to Cells (Genes to Cells) 23 ( 10 ) 904 - 914 2018.10

ISSN 13569597

© 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd In bacteria, a polymer of inorganic phosphate (Pi) (inorganic polyphosphate; polyP) is enzymatically produced and consumed as an alternative phosphate donor for adenosine triphosphate (ATP) production to protect against nutrient starvation. In vertebrates, polyP has been dismissed as a “molecular fossil” due to the lack of any known physiological function. Here, we have explored its possible role by producing transgenic (TG) mice widely expressing Saccharomyces cerevisiae exopolyphosphatase 1 (ScPPX1), which catalyzes hydrolytic polyP degradation. TG mice were produced and displayed reduced mitochondrial respiration in muscles. In female TG mice, the blood concentration of lactic acid was enhanced, whereas ATP storage in liver and brain tissues was reduced significantly. Thus, we suggested that the elongation of polyP reduces the intracellular Pi concentration, suppresses anaerobic lactic acid production, and sustains mitochondrial respiration. Our results provide an insight into the physiological role of polyP in mammals, particularly in females.

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Retrospective multicenter study of leaving the placenta in situ for patients with placenta previa on a cesarean scar

Miyakoshi K., Otani T., Kondoh E., Makino S., Tanaka M., Takeda S.

International Journal of Gynecology and Obstetrics (International Journal of Gynecology and Obstetrics) 140 ( 3 ) 345 - 351 2018.03

ISSN 00207292

© 2017 International Federation of Gynecology and Obstetrics Objective: To investigate maternal outcomes after leaving the placenta in situ for placenta accreta spectrum (PAS) disorders in patients with placenta previa on a cesarean delivery scar. Methods: The present retrospective study reviewed medical records from women with placenta previa on a cesarean scar underwent perinatal care at secondary- or tertiary-level perinatal centers in Japan between January 1, 2010, and December 31, 2014. Perinatal management was conducted based on each leading obstetrician's discretion. The primary outcome was success of the leaving the placenta in situ approach for PAS disorders (defined as preserving the uterus without hysterectomy). Results: Of 178 eligible centers, 126 (71%) participated in this study; data from 613 patients were included. Of these, 41 had the placenta left in situ owing to PAS disorders and follow-up data were available for 36 women. Leaving the placenta in situ was successful in 25 (69%) patients, with placental resorption occurring postpartum (median 89 days; range 6–510). Hysterectomy was performed for 11 patients, primarily owing to hemorrhage and/or infection (median 30 days; range 0–95 days, postpartum). Conclusion: Leaving the placenta in situ, with close postpartum follow-up for at least several months, could be a uterus-preserving option for patient with PAS disorders.

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Cover Image, Volume 176A, Number 1, January 2018

Ikenoue S., Miyakoshi K., Ishii T., Sato Y., Otani T., Akiba Y., Kasuga Y., Ochiai D., Matsumoto T., Ichihashi Y., Matsuzaki Y., Tachikawa K., Michigami T., Nishimura G., Ikeda K., Hasegawa T., Tanaka M.

American journal of medical genetics. Part A (American journal of medical genetics. Part A) 176 ( 1 ) 2018.01

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Discordant fetal phenotype of hypophosphatasia in two siblings

American Journal of Medical Genetics, Part A (American Journal of Medical Genetics, Part A) 176 ( 1 ) 171 - 174 2018.01

ISSN 15524825

© 2017 Wiley Periodicals, Inc. Hypophosphatasia (HPP) is an autosomal recessive metabolic disorder with impaired bone mineralization due to mutations in the ALPL gene. The genotype-phenotype correlation of this disorder has been widely described. Here, we present two affected siblings, whose fetal phenotypes were discordant. A 31-year-old Japanese woman, G0P0, was referred to our institution because of fetal micromelia. After obstetric counseling, the pregnancy was terminated at 21 weeks’ gestation. Post-mortem radiographs demonstrated severely defective mineralization of the skeleton. The calvarial, spinal, and tubular bones were mostly missing. Only the occipital bones, mandible, clavicles, ribs, one thoracic vertebra, ilia, and tibia were relatively well ossified. The radiological findings suggested lethal HPP. Genetic testing for genomic DNA extracted from the umbilical cord identified compound heterozygous mutations in the ALPL gene (c.532T>C, p.Y178H; c.1559delT, p.Leu520Argfs*86). c.532T>C was a novel variant showing no residual activity of the protein by the functional analysis. The parents were heterozygous carriers. In the next pregnancy, biometric values on fetal ultrasonography at 20 and 26 weeks’ gestation were normal. At 34 weeks, however, a small chest and shortening of distal long bones came to attention. The neonate delivered at 41 weeks showed serum ALP of <5U/L. Radiological examination showed only mild thoracic hypoplasia and metaphyseal mineralization defects of the long bones. ALP replacement therapy was introduced shortly after birth, and the neonate was discharged at day 22 without respiratory distress. Awareness of discordant fetal phenotypes in siblings with HPP precludes a diagnostic error, and enables early medical intervention to mildly affected neonates.

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Human amniotic fluid stem cells: Therapeutic potential for perinatal patients with intractable neurological disease

Ochiai D., Masuda H., Abe Y., Otani T., Fukutake M., Matsumoto T., Miyakoshi K., Tanaka M.

Keio Journal of Medicine (Keio Journal of Medicine) 67 ( 4 ) 57 - 66 2018

ISSN 00229717

© 2018 by The Keio Journal of Medicine. Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis. In vitro culture of these autologous AFS during pregnancy would make them available for use soon after birth. Hypoxic-ischemic encephalopathy (HIE) and myelomeningocele (MMC) are neonatal conditions that cause permanent neurological disability, for which the treatment options are extremely limited. Experiments using animal models of HIE and MMC and human clinical trials have demonstrated that MSCs, including AFS, have beneficial effects on the central nervous system through paracrine influences, indicating that autologous AFS treatment may be applicable for intractable neurological diseases, including HIE and MMC, during the perinatal period. In this review, we focus on recent research related to the therapeutic potential of AFS for perinatal neurological diseases such as HIE and MMC.

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Lower serum total bilirubin concentration is associated with higher prevalence of gestational diabetes mellitus in Japanese pregnant women

Nishimura T., Tanaka M., Saisho Y., Miyakoshi K., Tanaka M., Itoh H.

Endocrine Journal (Endocrine Journal) 65 ( 12 ) 1199 - 1208 2018

ISSN 09188959

©The Japan Endocrine Society. We aimed to clarify the pathophysiological significance of total bilirubin (TB) in gestational diabetes mellitus (GDM). This was a cross-sectional study that included 616 pregnant Japanese women (368 normal glucose tolerance [NGT] and 248 GDM). Serum TB concentration, homeostasis model assessment of insulin resistance (HOMA-IR), and other clinical parameters were compared in NGT and GDM women. TB concentration was also compared according to the number of abnormal OGTT values. Logistic regression analysis was used to evaluate the association between TB and GDM prevalence. A multiple linear regression model was used to evaluate the association between TB and HOMA-IR. TB concentrations were significantly lower in GDM women than in NGT women. This result did not change after adjustments for TB sampling timing were made. Out of 248 GDM women, the prevalences of 1-and 2/3-abnormal OGTT values (1-and 2/3-AV) GDM were 72.2% (n = 179) and 27.8% (n = 69), respectively. In the multiple comparisons, TB concentrations were significantly lower in women with 2/3-AV GDM than in women with NGT and 1-AV GDM. Multiple logistic regression analysis showed that TB was a significantly associated factor for 2/3-AV, but not for total GDM. HOMA-IR was significantly higher in GDM women than in NGT women. The univariate, but not multivariate, analysis showed that TB was a significantly associated factor for HOMA-IR. Our findings suggest that hypobilirubinemia may be involved in the pathogenesis of GDM.

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Successful Pregnancy After Sacrectomy Combined With Chemotherapy and Radiation for Ewing Sarcoma

Kakogawa Jun, Nako Takafumi, Kawamura Kazuhiro, Nakamura Shin, Mochiduki Ayako, Kanayama Naohiro, Tanaka Mamoru

Journal of Pediatric and Adolescent Gynecology 28 ( 3 ) e79 - e81 2015.06

ISSN 1083-3188

Ewing sarcoma is considered to have a poor prognosis. Recent advances in multidisciplinary management have resulted in a marked improvement in long-term survival. Case: We describe a case of successful pregnancy in a patient who underwent sacrectomy combined with multi-agent chemotherapy and radiotherapy for Ewing sarcoma. The patient was diagnosed with Ewing sarcoma of the sacrum at the age of 16. The ovaries were transposed, the uterus was shielded, and a gonadotropin-releasing hormone agonist was used during treatment to protect ovarian function. The patient spontaneously conceived at the age of 27. After an uneventful pregnancy, the patient delivered a healthy neonate at term by cesarean section. Summary and Conclusions: Successful pregnancy and delivery can be achieved after multi-modality treatment with pretreatment intervention for fertility preservation.

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Intracranial sonographic features demonstrating in utero development of hemorrhagic brain damage leading to schizencephaly-associated COL4A1 mutation

Matsumoto Tadashi, Miyakoshi Kei, Fukutake Marie, Ochiai Daigo, Minegishi Kazuhiro, Tanaka Mamoru

Journal of Medical Ultrasonics 2015.01

ISSN 1346-4523

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Analysis of late-onset ovarian insufficiency after ovarian surgery

Takae Seido, Kawamura Kazuhiro, Sato Yorino, Nishijima Chie, Yoshioka Nobuhito, Sugishita Yodo, Horage Yuki, Tanaka Mamoru, Ishizuka Bunpei, Suzuki Nao

PLoS ONE 9 ( 5 ) 2014.05

The primary objectives of the present study are to determine the period of onset of ovarian insufficiency after surgery and to confirm potential risk factors for ovarian insufficiency after surgery for the removal of benign ovarian cysts. Data were obtained from 75 patients who underwent surgery for benign ovarian cysts prior to the onset of ovarian insufficiency. Our analysis included 835 ovarian insufficiency patients who were referred to our institution from July 2003 to July 2013. Several epidemiological parameters of ovarian insufficiency after surgery (age at operation, period of onset of ovarian insufficiency, operation procedure, and pathological diagnosis) were investigated. Of the 835 patients who had ovarian insufficiency, 75 patients (9.0%) underwent ovarian surgery before the onset of ovarian insufficiency. Of those 75 patients, 66 patients (88.0%) underwent cystectomy. For the majority of the 75 patients the surgical indication was the presence of endometriotic cysts (57 patients; 76.0%). Twelve patients (16.0%) underwent multiple surgeries (all bilateral cystectomies). The mean age of the patients at the time of surgery was 27.8±5.5 years-old, and the mean period of onset of ovarian insufficiency was 5.8±3.8 years. In patients with cystectomy, the patient's age at the time of surgery and period of onset of ovarian insufficiency was well-correlated (coefficient of correlation; hemilateral endometriotic cystectomy: 20.64, bilateral endometriotic cystectomy: 20.61, and multiple endimetriotic cystectomy: 20.40). We found that cystectomy of endometriotic cysts is the potential risk factor for ovarian insufficiency after surgery, at times, the onset of ovarian insufficiency long after cystectomy. Therefore, it is important to monitor ovarian reserve for an extended period of time after ovarian surgery. It is particularly important to monitor ovarian reserve long-term for patients who wish to conceive in the future and to suggest a variety of infertility treatments appropriate for their ovarian reserve. © 2014 Takae et al.

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Compilation of copy number variants identified in phenotypically normal and parous Japanese women

Migita Ohsuke, Maehara Kayoko, Kamura Hiromi, Miyakoshi Kei, Tanaka Mamoru, Morokuma Seiichi, Fukushima Kotaro, Shimamoto Tomihiro, Saito Shigeru, Sago Haruhiko, Nishihama Keiichiro, Abe Kosei, Nakabayashi Kazuhiko, Umezawa Akihiro, Okamura Kohji, Hata Kenichiro

Journal of Human Genetics 59 ( 6 ) 326 - 331 2014

ISSN 1434-5161

With increasing public concern about infertility and the frequent involvement of chromosomal anomalies in miscarriage, analyses of copy number variations (CNVs) have been used to identify the genomic regions responsible for each process of childbearing. Although associations between CNVs and diseases have been reported, many CNVs have also been identified in healthy individuals. Like other types of mutations, phenotypically indefinite CNVs may have been retained and accumulated during anthropogenesis. Therefore to distinguish causative variants from other variants is a formidable task. Furthermore, because previous studies have predominantly focused on European and African populations, comprehensive detection of common Asian CNVs is eagerly awaited. Here, using a high-resolution genotyping array and samples from 411 Japanese women with normal parity without significant complications, we have compiled 1043 copy number variable regions. In total, the collected regions cover 164 Mb, or up to 0.5% of the genome. The copy number differences in these regions may be irrelevant not only to infertility but also to a wide range of diseases. The utility of this resource in reducing the candidate pathogenetic variants, especially in Japanese subjects, is also demonstrated. © 2014 The Japan Society of Human Genetics. All rights reserved.

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Fetal stomach paracentesis in combined duodenal and esophageal atresia

Kadohira Ikuko, Miyakoshi Kei, Shimojima Naoki, Matsumoto Tadashi, Minegishi Kazuhiro, Tanaka Mamoru, Kuroda Tatsuo, Yoshimura Yasunori

Journal of Medical Ultrasonics 41 ( 3 ) 397 - 400 2014

ISSN 1346-4523

Fetuses with concomitant duodenal atresia (DA) and esophageal atresia (EA) might develop in utero gastric rupture as well as neonatal respiratory complication due to dilated stomach and duodenum. Our patient with the typical "double bubble" appearance was highly suspected to have DA in the second trimester. Follow-up examinations revealed a massively dilated stomach and duodenum with a dilated distal esophagus, indicating concomitant DA and EA. With advancing pregnancy, the fetal abdomen progressively increased in size by retention of fluid in the closed loop of DA and EA. To avoid gastric perforation, prenatal stomach paracentesis using an ultrasound-guided needle was performed three times until delivery. A male neonate born at 37 weeks gestation showed no respiratory complication. Perinatal clinical features and operative findings revealed combined DA and EA (gross type A). He was successfully managed with duodenoduodenostomy, followed by esophago-esophagostomy. On fetal sonography, the marked "double bubble" appearance and the cystic structure presenting peristalsis-like movement above the diaphragm were indicative of concomitant DA and EA. Fetal stomach paracentesis could contribute to the improvement of perinatal outcomes in fetuses with this pathological condition. © 2014 The Japan Society of Ultrasonics in Medicine.

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Regulation of preimplantation embryo development in mice by FMS-like tyrosine kinase 3 ligand

Nishijima Chie, Kawamura Kazuhiro, Okamoto Naoki, Sato Yorino, Kawamura Nanami, Ishizuka Bunpei, Tanaka Mamoru, Suzuki Nao

Journal of Mammalian Ova Research 31 ( 1 ) 45 - 51 2014

ISSN 1341-7738

Successful development of preimplantation embryos is essential for reproduction. Growth factors secreted by reproductive tracts are important for the development of preimplantation embryos. FMS-like tyrosine kinase 3 (FLT3) is a tyrosine kinase receptor related to colony-stimulating factor-1 receptor and c-KIT, promoting preimplantation embryo development following their ligand binding. We found expression of FLT3 ligand transcripts in the oviducts and uteri of pregnant mice. The transcripts for its receptor, FLT3, were detectable throughout the early embryonic stages with an increase after the eight-cell stage. In contrast, the expression of FLT3 ligand was negligible after the morula stage, suggesting potential paracrine actions of FLT3 ligand produced by the reproductive tracts. Treatment with FLT3 ligand promoted the development of two-cell embryos to the morula and blastocyst stages in a dose-dependent manner with increases in cell proliferation, but not inhibition of cell survival. The effects of FLT3 ligand were blocked by a FLT3 receptor inhibitor, TCS359. Studies using specific inhibitors demonstrated the potential involvement of the PI3K pathway in mediating FLT3 ligand actions. Our findings suggest that the FLT3 ligand/FLT3 signaling system plays important paracrine roles during the development of preimplantation embryos. ©2014 Japan Society for Ova Research.

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