Starmerella kisarazuensis f.a., sp. nov., a novel yeast isolated from Trifolium pratense flowers.

Three yeast isolates, NBRC 115909T, NBRC 115910 and NBRC 116270, were isolated from Trifolium pratense (red clover) flowers collected from Kisarazu, Chiba, Japan. Analysis of the sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions revealed that these isolates represent a single novel species within the genus Starmerella. Also, no ascospore formation was observed. The yeast isolates were closely related to Starmerella vitae UWOPS 00-107.2T and Starmerella bombi NRRL Y-17081T. They differed from S. vitae, the most closely related species with a validly published name, by ten nucleotide substitutions with two gaps in the D1/D2 domains and 20 nucleotide substitutions in the ITS region. Moreover, the three isolates exhibited distinct phenotypic characteristics from the closely related species. Therefore, we suggest that these three isolates represent a novel species, designated as Starmerella kisarazuensis f.a., sp. nov. The holotype is NBRC 115909T (isotype: CBS 18485T).

A 41-Year-Old Woman with Spontaneous Hemoperitoneum in Pregnancy at 28 Weeks.

BACKGROUND Spontaneous hemoperitoneum in pregnancy (SHiP), defined as nontraumatic, acute intra-abdominal bleeding during pregnancy or the postpartum period, is a serious life-threatening complication to mother and child. Endometriosis is a major risk factor for SHiP. This study presents the case of a 41-year-old woman with adenomyosis who developed hemoperitoneum due to endometriosis at 28 weeks of pregnancy. CASE REPORT The patient was a 41-year-old woman (gravida 1, para 0) who conceived via artificial insemination. She had diffuse adenomyosis in the posterior uterine wall and was admitted to our hospital at 12 weeks of gestation with persistent lower abdominal pain. She had started treatment with hydroxyprogesterone caproate to reduce the focal inflammation of adenomyosis. At 28 weeks of gestation, she developed severe lower abdominal pain, and ultrasonography revealed prolonged fetal heart rate deceleration. An emergency cesarean delivery was performed, and a 907 g female infant with an Apgar score of 2/3 was delivered. Umbilical artery blood pH was 7.15. Bleeding from the veins surrounding an endometriotic lesion on the posterior wall of the uterus was observed, and SHiP was diagnosed. CONCLUSIONS Pregnancies complicated by endometriosis or adenomyosis require perinatal management, considering the possibility of SHiP complication. If acute abdominal pain and fetal heart rate deceleration occur during pregnancy, a search for intra-abdominal bleeding should be performed and emergent open hemostasis or cesarean delivery should be considered.

Impact of maternal late hospital arrival on adverse outcome of offspring affected by placental abruption: A regional multicenter nested case-control study in Japan.

AIMS: To elucidate the influence of the time-intervals between the onset and arrival (TIME 1), onset and delivery (TIME 2), and the decision to deliver and delivery (TIME 3) on severe adverse outcomes of offspring born to mothers complicated by placental abruption outside the hospital. METHODS: This is a multicenter nested case-control study about placental abruption at Fukui Prefecture, a regional area in Japan, through 2013 to 2017. Multiple pregnancy, fetal or neonatal congenital abnormality, and unknown detailed information at onset of placental abruption were excluded. A composite of perinatal death and cerebral palsy or death at 18-36 months of corrected age was defined as the adverse outcome. The relationship between time-intervals and the adverse outcome was analyzed. RESULTS: The 45 subjects for analysis were divided into two groups, including a group with and without adverse outcome (poor, n = 8; and good, n = 37). TIME 1 was longer in the poor group (150 vs. 45 min, p < 0.001). A subgroup analysis targeted to 29 cases with preterm birth at the third trimester indicates that TIME 1 and TIME 2 were longer in the poor group (185 vs. 55 min, p = 0.02; and 211 vs. 125 min, p = 0.03), while TIME 3 was shorter in the poor group (21 vs. 53 min, p = 0.01). CONCLUSIONS: Long time-intervals between onset and arrival or onset and delivery may be correlated with perinatal death or cerebral palsy in surviving infants affected by placental abruption.

Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging.

The ovarian microenvironment is critical for follicular development and oocyte maturation. Maternal conditions, including polycystic ovary syndrome (PCOS), endometriosis, and aging, may compromise the ovarian microenvironment, follicular development, and oocyte quality. Chronic low-grade inflammation can induce oxidative stress and tissue fibrosis in the ovary. In PCOS, endometriosis, and aging, pro-inflammatory cytokine levels are often elevated in follicular fluids. In women with obesity and PCOS, hyperandrogenemia and insulin resistance induce ovarian chronic low-grade inflammation, thereby disrupting follicular development by increasing oxidative stress. In endometriosis, ovarian endometrioma-derived iron overload can induce chronic inflammation and oxidative stress, leading to ovarian ferroptosis and fibrosis. In inflammatory aging (inflammaging), senescent cells may secrete senescence-associated secretory phenotype factors, causing chronic inflammation and oxidative stress in the ovary. Therefore, controlling chronic low-grade inflammation and fibrosis in the ovary would present a novel therapeutic strategy for improving the follicular microenvironment and minimizing ovarian dysfunction.

Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast.

During placentation, placental cytotrophoblast (CT) cells differentiate into syncytiotrophoblast (ST) cells and extravillous trophoblast (EVT) cells. In the placenta, the expression of various genes is regulated by the Hippo pathway through a transcription complex, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-TEA domain transcription factor (TEAD) (YAP/TAZ-TEAD) activity. YAP/TAZ-TEAD activity is controlled by multiple factors and signaling, such as cAMP signaling. cAMP signaling is believed to be involved in the regulation of trophoblast function but is not yet fully understood. Here we showed that YAP/TAZ-TEAD expressions and their activities were altered by cAMP stimulation in BeWo cells, a human choriocarcinoma cell line. The repression of YAP/TAZ-TEAD activity induced the expression of ST-specific genes without cAMP stimulation, and transduction of constitutively active YAP, i.e. YAP-5SA, resulted in the repression of 8Br-cAMP-induced expressions of ST-specific genes in a TEAD-dependent manner. We also investigated the role of YAP/TAZ-TEAD in maintaining CT cells and their differentiation into ST and EVT cells using human trophoblast stem (TS) cells. YAP/TAZ-TEAD activity was involved in maintaining the stemness of TS cells. Induction or repression of YAP/TAZ-TEAD activity resulted in marked changes in the expression of ST-specific genes. Using primary CT cells, which spontaneously differentiate into ST-like cells, the effects of YAP-5SA transduction were investigated, and the expression of ST-specific genes was found to be repressed. These results indicate that the inhibition of YAP/TAZ-TEAD activity, with or without cAMP stimulation, is essential for the differentiation of CT cells into ST cells.

Laparoscopic surgery-associated massive subcutaneous emphysema requiring mechanical ventilation in a patient with endometriosis: a case report.

Although subcutaneous emphysema is a common benign complication of laparoscopic surgery, airway obstruction can occur due to pharyngeal emphysema when it extends to the neck. Here, we report a case of subcutaneous emphysema extending to the neck that required mechanical ventilation in a 51-year-old patient with endometriosis and severe adhesions during total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. Although surgical or disease-specific risk stratification has not yet been established, the severe adhesions due to endometriosis and massive peritoneal defect due to the procedure might lead to the fragility of the subcutaneous tissue, resulting in a massive subcutaneous emphysema. This study highlights the importance of preoperative risk assessment in addition to intraoperative and postoperative monitoring for ventilation disorders and subcutaneous emphysema.

Acute type B aortic dissection in a pregnant woman with undiagnosed Marfan syndrome: A case report and review of the literature.

Aortic dissection during pregnancy is rare but can be life-threatening to both the mother and the foetus. Marfan syndrome is a major risk factor for acute aortic dissection during pregnancy. Here, we present the case of a woman who had not been diagnosed with Marfan syndrome prior to pregnancy and who developed acute type B dissection at 32 weeks of gestation. The maternal hemodynamic status was stable, and foetal well-being was ensured. However, under conservative treatment, the dissection extended to the descending aorta, reaching the bilateral iliac artery 2 days later. Due to foetal distress, preterm delivery was performed via caesarean section. The primary treatment of type B aortic dissection is conservative medical treatment, with the goals of hemodynamic stabilisation, minimising the extent of the dissection and decreasing the risk of rupture. However, type B aortic dissection, even the uncomplicated type, in pregnant women may require early and aggressive obstetric interventions to improve maternal and foetal prognoses.

The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini-review.

BACKGROUND: The process of follicle development is tightly regulated by pituitary gonadotropins (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) and intraovarian regulators (eg, steroids, growth factors, and cytokines). METHODS: This review outlines recent findings on the mechanisms of human follicle development, based on the research on animal models such as mice, rats, cows, and sheep. MAIN FINDINGS: Phosphatidylinositol 3-kinase/protein kinase B signaling pathway and anti-Müllerian hormone are involved in primordial follicle activation during the gonadotropin-independent phase. The intraovarian regulators, such as androgen, insulin-like growth factor system, activin, oocyte-derived factors (growth differentiation factor-9 and bone morphogenetic protein 15), and gap junction membrane channel protein (connexin), play a central role in the acquisition of FSH dependence in preantral follicles during the gonadotropin-responsive phase. Antral follicle development can be divided into FSH-dependent growth and LH-dependent maturation. The indispensable tetralogy for follicle selection and final maturation of antral follicles involves (a) acquisition of LH dependence, (b) greater capacity for E2 production, (c) activation of the IGF system, and (d) an antiapoptotic follicular microenvironment. CONCLUSION: We reproductive endocrinologists should accumulate further knowledge from animal model studies to develop methods that promote early folliculogenesis and connect to subsequent gonadotropin therapy in infertile women.

Herlyn-Werner-Wunderlich syndrome with cervical atresia complicated by ovarian endometrioma: A case report.

Herlyn-Werner-Wunderlich syndrome (HWWs) is a rare congenital malformation that involves uterus dideslphys, obstructed hemivagina and ipsilateral renal agenesis. The obstructed vagina affects menstrual flow and causes related clinical features after menarche. Pelvic endometriosis is one of the common complications of HWWs. Resection of the vaginal septum can release the obstruction and result in good outcomes. However, in the case of cervical atresia, a rare variant of HWWs, ipsilateral hysterectomy is recommended because it is difficult to canalize cervical atresia surgically. Here we present a case of HWWs with cervical atresia complicated with pelvic endometriosis. She was treated with laparoscopic ovarian cystectomy followed by hormonal therapy. Six months after surgery, there is no evidence of recurrence of endometrioma.

Endovascular trophoblast expresses CD59 to evade complement-dependent cytotoxicity.

In the human placenta, extravillous trophoblasts (EVTs) invade maternal decidual tissues (interstitial trophoblasts) and maternal spiral arteries (endovascular trophoblasts). Although endovascular trophoblasts are directly exposed to maternal blood containing complement components, they are not eliminated by complement-dependent cytotoxicity (CDC). In this study, we investigated the expression and possible function of CD59, one of the membrane-bound complement regulators, in EVTs. Immunohistochemistry of early embryo implantation sites revealed that CD59 was hardly expressed on interstitial trophoblasts, whereas it was intensely expressed on endovascular trophoblasts. Using the human EVT-like cell line Swan71, we established CD59-silencing Swan71 cells (Sw_CD59sh) and non-silencing control Swan71 cells (Sw_CTRsh). In vitro cell apoptosis assay showed that Sw_CD59sh cells were significantly more susceptible to CDC as compared to Sw_CTRsh. Our results suggest that CD59 confers some protection against maternal complement attack to the endovascular trophoblasts.

Versican V1 in human endometrial epithelial cells promotes BeWo spheroid adhesion in vitro.

The endometrium extracellular matrix (ECM) is essential for embryo implantation. Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and forms large ECM aggregates, can influence fundamental physiological phenomena, such as cell proliferation, adhesion and migration. The present study investigated the possible role of versican in human embryo implantation. Versican V1 expression and secretion in human endometrial epithelial cells (EECs) was most prominent in the mid-secretory phase. Versican expression in EECs significantly increased after treatment with estrogen and progesterone, but not by estrogen alone. We also established versican V1-overexpressing Ishikawa (endometrial cancer cell line) cells (ISKW-V1), versican V3-overexpressing (ISKW-V3) and control GFP-overexpressing (ISKW-GFP) Ishikawa cells. By the in vitro implantation model, the attachment ratio of BeWo (choriocarcinoma cell line) spheroids to the monolayer of ISKW-V1, but not of ISKW-V3, was found significantly enhanced compared with attachment to the ISKW-GFP monolayer. The conditioned medium derived from ISKW-V1 (V1-CM) also promoted the attachment of BeWo spheroids to the ISKW monolayer. However, this attachment-promoting effect was abolished when V1-CM was pretreated with chondroitinase ABC, which degrades chondroitin sulfate. Therefore, out of the ECM components, versican V1 may facilitate human embryo implantation.

Role of Versican in the Pathogenesis of Peritoneal Endometriosis.

CONTEXT: Sampson's theory cannot explain why only some cycling women develop peritoneal endometriosis. Few studies have focused on the pelvic peritoneum, which receives regurgitated endometrial tissues. We hypothesized that molecular alterations in the peritoneum are involved in the development of peritoneal endometriosis and conducted a microarray analysis to compare macroscopically normal peritoneum sampled from women with peritoneal endometriosis (endometriotic peritoneum) and those without (non-endometriotic peritoneum). Versican, a major proteoglycan component of the extracellular matrix, is one of the molecules up-regulated in endometriotic peritoneum. OBJECTIVE: To investigate the role of versican in peritoneal endometriosis. Design, Patients, and Main Outcome Measure: Endometriotic peritoneum and non-endometriotic peritoneum were subjected to RT-PCR, immunostaining, and Western blotting. The versican V1 isoform was stably transfected into Chinese hamster ovary cells (CHO-V1), and the effects of CHO-V1-derived conditioned medium (V1-CM) on primary human endometrial stromal cells were investigated with attachment, invasion, and proliferation assays. The effects of peritoneal fluid collected from endometriotic women (endometriotic PF) or cytokines/growth factors, which were shown to be elevated in endometriotic PF, on versican expression in a human peritoneal cell line (HMrSV5) were also examined. RESULTS: Versican V1 expression levels were significantly higher in endometriotic peritoneum. In vitro, V1-CM promoted attachment to the HMrSV5 cell monolayer as well as the Matrigel invasion of endometrial stromal cells. Although versican V1 expression was up-regulated by TGF-ß1 in HMrSV5 cells, it remained unchanged in endometriotic PF. CONCLUSIONS: Our results suggest the involvement of peritoneal versican in the development of peritoneal endometriosis.

Blood-brain barrier transport of an essential amino acid after cerebral ischemia reperfusion injury.

Under pathophysiological conditions such as -cerebral ischemia-reperfusion (IR), damage to cerebrovascular endothelial cells causes alterations in the blood-brain barrier (BBB) function that can exacerbate neuronal cell injury and death. Clarifying changes in BBB transport in the early period of IR is important for understanding BBB function during therapy after cerebral ischemia. The present study was aimed at clarifying changes during IR in the BBB transport of L-phenylalanine (Phe) as a substrate of L-type amino acid transporter 1. An IR model was produced in mice by blood recirculation following occlusion of the middle cerebral artery. Permeability of the BBB to [(3)H]Phe was measured after IR injury using the brain perfusion method. Confocal microscopy of the IR injury showed no brain penetration of fluorescent tracer, thus confirming BBB integrity during 45 min of ischemia. Tight junction opening was not observed at 30 min after reperfusion following ischemia for 45 min. At the time of IR, [(3)H]Phe uptake into the brain appeared saturated. The Michaelis constant and maximum transport velocity in the IR group was reduced by 22 % compared with those in controls. These results suggest that the intrinsic transport clearance of Phe is slightly decreased in the early phase of IR.