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Background: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs).Methods: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay.Results: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males.Conclusions: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs. [ABSTRACT FROM AUTHOR]

Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial ceils transplanted beneath the kidney capsule of NOD/SCID/γcnull immunodeficient mice. In addition to the endometrium-like structure hormone-dependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed non-invasively and quantitatively by in vivo bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule. [ABSTRACT FROM AUTHOR]

Preimplantation development is marked by four major events: the transition of maternal transcripts to zygotic transcripts, compaction, the first lineage differentiation into inner cell mass and trophectoderm, and implantation. The scarcity of the materials of preimplantation embryos, both in size (diameter < 100 m) and in quantity (only a few to tens of oocytes from each ovulation), has hampered molecular analysis of preimplantation embryos. Recent progress in RNA amplification methods and microarray platforms, including genes unique to preimplantation embryos, allow us to apply global gene expression profiling to the study of preimplantation embryos. Our gene expression profiling during preimplantation development revealed the distinctive patterns of maternal RNA degradation and embryonic gene activation, including two major transient waves of de novo transcription. The first wave corresponds to zygotic genome activation (ZGA). The second wave, mid-preimplantation gene activation (MGA), contributes dramatic morphological changes during late preimplantation development. Further expression profiling of embryos treated with inhibitors of transcription or translation revealed that the translation of maternal RNA is required for the initiation of ZGA, suggesting a cascade of gene activation from maternal RNA/protein sets to ZGA gene sets and thence to MGA gene sets. To date, several reports of microarray experiments using mouse and human preimplantation embryos have been published. The identification of a large number of genes and multiple signaling pathways involved at each developmental stage by such global gene expression profiling accelerates understanding of molecular mechanisms underlining totipotency/pluripotency and programs of early mammalian development. [ABSTRACT FROM AUTHOR]

The birth announced in 1997 of Dolly, the lamb cloned from the somatic mammary cells of an adult ewe, and the discovery of human embryonic stem cells in 1998 have been the most exciting developments in the biological sciences in the past decade. Reproductive somatic cell nuclear transfer (SCNT) in additional species has been inefficient in that relatively few births, harmful side effects and high fetal and neonatal death rates have resulted from many attempts. Ongoing debates about the ethics of reproductive SCNT have revealed that some researchers regard human reproductive SCNT as morally unacceptable in all circumstances, others see merit in reproductive SCNT in certain circumstances and others await more information before making judgment about the ethical status of the procedure. Regenerative medicine and emerging biotechnologies started to revolutionize the practice of medicine. Advances in stem cell biology, including embryonic and postnatal somatic stem cells, have made the prospect of tissue regeneration a potential reality. Mammal cloning experiments have provided new impetus to the prospect of regenerative medicine through stem cell research. The procedure of SCNT could be used to create the raw material to replace defective or senescent tissue as a natural extension of the biology of stem cells. Researchers working in reproductive medicine should consider the potential hope given to many patients against the requisite and ethically contentious creation of human blastocysts for therapeutic intent. [ABSTRACT FROM AUTHOR]

Human uterine endometrium repeats proliferation, differentiation (decidualization) and tissue breakdown during the menstrual period. Appropriate secretion of ovarian steroid hormones regulates these sequential endometrial remodeling cycles. While progesterone replacement therapy is adopted for endometrial dysfunction of differentiation, including recurrent impairment of implantation, no obvious effective results are obtained. Histone reversible acetylation, regulated by histone acetyltransferases and histone deacetylases plays a pivotal role in gene transcription. Although, in cells cultured with histone deacetylase inhibitors (HDACI), the expression of only about 2% of expressed genes is changed twofold or more compared with untreated control cells. Numerous previous works have demonstrated that HDACI affect cell proliferation/apoptosis in a variety of types of cells. To date, several HDACI are in phase I or phase II clinical trials as anti-cancer drugs. However, no reports have been found that HDACI is useful for transdifferentiation in human endometrium. Recently, we reported that HDACI could induce the expression of differentiation marker proteins, morphological change and functional cytodifferentiation in both human endometrial stromal and epithelial cells. In this review, we summarize the effect of HDACI against the human endometrial cytodifferentiation, indicating the possibility that HDACI can be used not only as an anticancer drug, but also as a transdifferentiation reagent, based on a new strategy. [ABSTRACT FROM AUTHOR]

Melatonin plays a critical role in a variety of mammalian reproductive processes not only acting on the central nervous system but also behaving as a peripheral physiologic regulator. To address the relevance of melatonin to the maintenance of pregnancy at the feto-maternal interface, we investigated the expression of two types of membrane melatonin receptors, MT1 and MT2, as well as arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), the two enzymes required for the conversion of serotonin to melatonin, in the human placenta and the effect of melatonin on the release of human chorionic gonadotropin (hCG) from cultured human trophoblast cells. RT-PCR analysis and DNA sequencing revealed that transcripts of MT1, MT2, AA-NAT, and HIOMT were present in the first-trimester human placenta. We also found that melatonin significantly potentiated hCG secretion at optimal concentrations. These results suggest that melatonin may regulate human placental function in a paracrine/autocrine manner, providing evidence for a novel role in human reproduction. [ABSTRACT FROM AUTHOR]

A case of non-communicating rudimentary uterine horn is presented and is a characteristic example of the way that surgical treatment can exacerbate dysmenorrhea by blocking retrograde menstruation. There is always some risk of missing the true diagnosis in cases of uterine abnormalities, even by direct inspection, but intraoperative laparoscopic ultrasonography can be an invaluable tool in defining anatomy. As laparoscopic resection has become the standard procedure for the treatment of unicornuate uterus, laparoscopic ultrasonography can be a useful tool for providing anatomical information to the operating surgeon about the patient. [ABSTRACT FROM AUTHOR]

Acetylation of histones is cooperatively regulated by two groups of enzymes, histone acetyltransferases and histone deacetylases. Histone acetylation status plays a fundamental role in the level of gene transcription; numerous studies have demonstrated that histone deacetylase inhibitors cause cell growth arrest, apoptosis, and differentiation in various cells including human mammary gland and endometrial cells by altering transcription of a small number of genes. A recent study has also shown that a highly acetylated histone status alters cell motility. After the present review of the published reports on the mechanisms underlying histone acetylation andin vitroeffects of histone deacetylase inhibitors, we conclude that this class of agents may have potential not only as anticancer drugs, but also as inducers of differentiation and/or motility for benign gynecologic conditions such as endometriosis and disorders of endometrial differentiation and dysfunction. (Reprod Med Biol 2005;4: 115–122) [ABSTRACT FROM AUTHOR]

Purpose: Color Doppler imaging permits the accurate localization of vessels and high-frequency pulsed Doppler ultrasonography has improved the resolution of flow velocity waveforms. In this study, intraovarian arterial blood flow before and after follicle rupture in the natural cycle was examined using transvaginal color flow Doppler imaging and changes in intraovarian arterial resistance in relation to the outcome of infertility treatment was analyzed. Methods: In a prospective study, 227 spontaneous cycles in 118 infertile patients who were undergoing infertility treatment at the division of Reproductive Medicine in our center were recruited in this study. The impedance to flow in intraovarian vessels was measured by means of transvaginal color flow Doppler imaging during the periovulatory period in the natural cycle of all patients. The pulsatility index (PI) of intraovarian arterial blood flow and pregnancy rate was evaluated. Results: On the basis of PI values before and after follicular rupture, 227 cycles were classified into severely decreased (113 cycles) and not severely decreased groups (114 cycles). The pregnancy rate per cycle in the severely decreased group was 18.6% (21/113), significantly higher than that in the not-severely decreased group (7/114; 6.1%, p = 0.004). The miscarriage rate was similar in the two groups. Conclusions: A reduction in intraovarian blood vessel resistance is necessary to achieve pregnancy in a natural cycle. [ABSTRACT FROM AUTHOR]

Cyclic ovarian follicular development is a complex process that involves proliferation, differentiation, and death of follicle cells. Gonadotropins produced by the pituitary gland have a central role in the regulation of these processes. In addition, a wide range of paracrine and autocrine factors produced in the reproductive organs have been proposed as regulators of reproductive functions. Components of the insulin-like growth factors (IGF) system are widely expressed in the female reproductive tract. The IGFs and their binding proteins play a significant role in several processes of reproductive physiology, including ovarian follicular development, oogenesis and oocyte maturation, ovulation, luteal function, follicular atresia, and testicular function. The majority of these physiological actions of the IGFs are believed to occur via activation of the IGF-I receptor, although the IGF-I effects are modulated by IGF binding proteins (IGFBPs). As much of the data obtained to date have been in the rodent reproductive organs, it may not be possible to directly extrapolate the results to the primate organs. There is a distinct species-difference in the gene expression and functional roles of the IGF-IGFBP system in reproductive organs. However, the disturbance of the IGF-IGFBP system in human reproductive physiology may lead to anovulation, disorders of androgen excess, infertility associated with implantation failure, and male infertility. Further research is needed in domestic animals to determine if manipulation of the IGF-IGFBP system may result in improved reproductive efficiency. As our understanding of the IGF-IGFBP system increases, the uses of human recombinant IGF peptides and IGFBPs as clinical therapy for disease states is becoming a reality. (Reprod Med Biol 2003; 2: 1–24). [ABSTRACT FROM AUTHOR]

Purpose: To determine whether there is any association between the expression of endometrial integrin αvβ3 and repeated IVF-ET failure and to examine the effect of danazol treatment on αvβ3 expression. Methods: This prospective study was performed using a semiquantitative immunohistochemical analysis on the staining intensity of αvβ3 in the mid-secretory endometria derived from 10 fertile women and 57 infertile patients with a history of repeated IVF-ET failures. Nine patients randomly selected from these 22 patients with unexplained infertility were then treated with oral danazol administration for 12 weeks and reexamined at the first mid-secretory phase after the danazol treatment. Result(s): The levels of endometrial αvβ3 expression were lower in 22 patients with unexplained infertility than in the fertile control and 35 patients with explained infertility. The 9 patients treated with danazol showed a significant increase in the αvβ3 staining. Conclusion(s): The significantly decreased expression of endometrial integrin αvβ3 suggested that functional, but not morphological, endometrial defect may be one of the causes for the patients with unexplained infertility. Danazol may have a therapeutic potential in improving endometrial function together with up-regulation of αvβ3. [ABSTRACT FROM AUTHOR]

We investigated the contribution of neutrophils to prostaglandin (PG)F[sub 2α]-induced luteolysis and the role of reactive oxygen species (ROS) as potential mediators of neutrophil accumulation in regressing corpora lutea of superovulated rats. On day 8 of pseudopregnancy, subcutaneous injection of PGF[sub 2α] (500 µg) significantly increased rhodamine 6G-labeled leukocyte adhesion in luteal venules, as observed by intravital microscopy. Neutrophil accumulation was confirmed by significantly increased myeloperoxidase (MPO) activity. Pretreatment with anti-leukocyte antibody (CD18-directed monoclonal antibody, WT-3) significantly inhibited the PGF[sub 2α]-induced increases in adherent leukocytes and MPO activity. Anti-leukocyte antibody also maintained serum progesterone concentrations. Pretreatment with oxygen free radical scavengers, superoxide dismutase (50,000 U/kg) and catalase (90,000 U/kg), also attenuated these PGF[sub 2α]-induced alterations. Corpora lutea preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescent indicator for determining intracellular ROS generation, exhibited an increase in fluorescence after PGF[sub 2α] treatment. These findings suggest that leukocyte-endothelium interactions mediated by ROS generation are important in PGF[sub 2α]-induced luteolysis in rats. [ABSTRACT FROM AUTHOR]

The present study was undertaken to investigate the expression and function of β[sub 1] integrins in human endometrium and decidua. Fluorescence-activated flow cytometry demonstrated the greater expression of the β[sub 1] , α[sub 1] , α[sub 2] , and α[sub 5] subunits of the β[sub 1] integrin family in cultured stromal cells from the midsecretory phase than in those of the early proliferative phase. The addition of estradiol (E[sub 2] ) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of β[sub 1] integrins in vitro. The immunohistochemical distribution of β[sub 1] integrins demonstrated predominantly glandular epithelial staining in the proliferative phase, and stromal and glandular staining in the midsecretory phase. Flow cytometry also demonstrated the expression of β[sub 1] , α[sub 1] , α[sub 2] , α[sub 3] , α[sub 5] , and α[sub 6] subunits of β[sub 1] integrin family in cultured decidual cells. Immunohistochemistry confirmed the β[sub 1] integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In the subsequent experiment, the effects of antibodies against specific β[sub 1] integrin heterodimers on mouse embryo attachment and spreading were tested to identify the role of β[sub 1] integrins in early implantation. We developed assays for the attachment of mouse embryos and for trophoblastic spreading on cultured human decidual cells. The addition of antibodies directed against β[sub 1] and α integrin subunits to cultured decidual cells did not affect the rates of hatching or attachment of the blastocysts, whereas the outgrowth of embryos on the decidual cells was inhibited by their antibodies in a dose-dependent manner. Thus, β[sub 1] integrin in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 31-year-old pregnant woman who was admitted to a hospital for potential cardiac anomaly on obstetric screening ultrasound during 28 weeks of gestation. Findings of Color Doppler sonography reveal a truncus arteriosus (TA) associated with interrupted aortic arch (IAA). It indicates that no remarkable changes were detected in fetal cardiac function.

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder characterized by multiple venous malformations (VMs) of the skin, gastrointestinal tract, and other organs. To date, several cases of sporadic BRBNS involving various parts of the pregnant woman's body have been reported; however, BRBNS in pregnancy with spinal epidural involvement has not been reported. Here, we describe the clinical features andmanagement of familial BRBNS in pregnancy. The patient presented withmultiple VMs on her head, neck, floor of the mouth, trunk, leg, foot, and vulva and spinal epidural lesions. The patient's mother and sister also exhibited multiple VMs similar lesions, indicating a familial formof BRBNS. Cesarean section under general anesthesia was performed, and a healthymale neonate was delivered. The mother's postoperative course was uneventful and her VMs decreased in size after delivery. Physicians should consider the possibility of systemic diseases and familial inheritance in cases of VMs. [ABSTRACT FROM AUTHOR]

Congenitally corrected transposition of the great arteries (cTGA) is an uncommon cardiac malformation characterized by discordant atrioventricular and ventriculoarterial connections. Most cases of cTGA are associated with cardiac anomalies. As the ventricular outflow tract may appear to arise correctly from the right and left ventricles, cases of cTGA with a mild associated anomaly are rarely detected prenatally. Parallel vessels are evident in cTGA, but this sign is also present in complete TGA. We report a case of cTGA diagnosed in utero at 29 weeks' gestation. The fetus was diagnosed as TGA and referred to our hospital at 28 weeks' gestation. cTGA was found at 29 weeks' gestation in our hospital, and no additional cardiac anomalies were seen prenatally. After birth, patent ductus arteriosus with bidirectional flow was present. Careful examination of the four-chamber view suggested atrioventricular discordance. Identification of a parallel course of the great vessels, with the aorta anterior and to the left of the pulmonary trunk ( l-transposition), may help accurate prenatal diagnosis of cTGA. [ABSTRACT FROM AUTHOR]

The Great Eastern Japan Earthquake of 2011 and consequent tsunami affected many IVF clinics in northeastern Japan. Twelve clinics lost at least one embryo, but all the frozen embryos stored in liquid nitrogen tanks were safe. Emergency power supply is the first priority issue in an unpredictable natural disaster. [ABSTRACT FROM AUTHOR]

We present a case of hemifacial microsomia, first detected by prenatal sonography and confirmed by ultrafast magnetic resonance (MR)imaging. A 26-year-old patient was referred to our hospital at 20 weeks of gestation because of unilateral right-sided ventriculomegaly and of a possible ventriculoseptal defect (VSD). Our sonographic examination suggested a right orbital hypoplasia and a hemiatrophy of the nose. The ultrafast T2-weighted single-shot fast-spin echo MR imaging, demonstrated a right ear hypoplasia (microtia), a right orbital hypoplasia, and a right renal hypoplasia. Epibulbar dermoid or conjunctival lipodermoid were not recognized. The fetus was prenatally diagnosed as hemifacial microsomia. Termination of pregnancy was performed at 21 weeks gestation, and a male baby weighing 342g was stillborn. The baby showed facial asymmetry, including hemiatrophy of the right nose, and right ear hypoplasia. Autopsy revealed a 2mm area of VSD, agenesis of the right kidney and ureter, pancreatic and renal aberration into right adrenal gland, thymus hypoplasia and an unfixed ascending colon without intestinal malrotation. To the best of our knowledge, this is the first report of prenatal diagnosis for hemifacial microsomia using fetal MR imaging. In our case, fetal MR imaging has evolved into a powerful diagnostic tool, for the accurate prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Massive hepatic infarction associated with pregnancy is extremely rare, but is potentially fatal. A 35-year-old primigravida with mild preeclampsia developed acute right upper quadrant pain and marked elevation of liver enzymes at 26 weeks' gestation. After emergent cesarean section, her condition was complicated by oliguric renal failure and pulmonary edema with further deterioration of hepatic function (aspartate transaminase 4339 IU/L; alanine transaminase 3489 IU/L; lactate dehydrogenase 10780 IU/L). The contrast-enhanced computed tomography revealed non-enhancing low attenuation throughout the right lobe of liver, compatible with infarction. Continuous hemodiafiltration was initiated as renal support on postpartum day one. However, excessive fluid accumulation persisted, and she developed severe edema formation in both lung and systemic body surface. To ameliorate microvascular endothelial injury, corticosteroid therapy was begun on postpartum day five. Following treatment initiation, her renal and hepatic function showed steady improvement, accompanied by drastic resolution of edema formation. She was discharged five weeks postpartum with no additional treatment, and is without sequelae six months later. Massive hepatic infarction should be considered in preeclamptic patients who present acute abdominal pain and severe hepatic dysfunction, and continuous hemodiafiltration with corticosteroid therapy may improve the maternal outcome. [ABSTRACT FROM AUTHOR]