Evaluation of the holding-up uterus technique for placenta accreta spectrum cesarean hysterectomy in shocked patients with a high shock index: a case series study.

BACKGROUND: Placenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the "Holding-up uterus" surgical technique with a shock index (S.I.) > 1.5. METHODS: Twelve patients who underwent PAS cesarean hysterectomy were included in the study. RESULTS: Group I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5. CONCLUSIONS: The study found that the "Holding-up uterus" technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.

Prognostic value of 18F-FDG PET in uterine cervical cancer patients with stage IIICr allocated by imaging.

The effect on survival of radiographic lymph node metastasis in uterine cervical cancer patients is more important than before, even though its prognostic value not been well investigated. The aim of our study is to evaluate the prognostic potential of 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) compared with Computed Tomography (CT) in uterine cervical cancer patients with stage IIICr allocated by imaging. Fifty-five patients with biopsy-proven primary cervical cancer underwent definitive radiation therapy for stages IIB-IVB of The International Federation of Gynecology and Obstetrics (FIGO) 2018 classifications. The prognostic performance of pretreatment 18F-FDG PET and CT for assessing lymph node metastasis was evaluated by two experienced readers. The PET and CT findings were correlated with the risk of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier survival curves showed that PFS was significantly worse in patients with positive lymph nodes on 18F-FDG PET than in those patients with negative lymph nodes on 18F-FDG PET (p = 0.003), whereas there was no significant difference in PFS between patients with lymph nodes sized ≥ 1 cm and those sized < 1 cm (p = 0.140). Univariate analysis showed that positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006), whereas lymph node size was not significantly associated with poor PFS (p = 0.145). In multivariate analysis, positive lymph nodes on 18F-FDG PET was significantly associated with poor PFS (p = 0.006) and was an independent prognostic factor for PFS. 18F-FDG PET offers high prognostic value for patients with stage IIICr allocated by imaging compared with CT, suggesting that 18F-FDG PET might be useful in clinical staging decisions and thus promote optimal diagnostic and therapeutic strategies.

Longitudinal changes in attention bias to infant crying in primiparous mothers.

Introduction: Infant stimuli attract caregiver attention and motivate parenting behavior. Studies have confirmed the existence of attentional bias toward infant face stimuli; however, relatively little is known about whether attentional bias exists for infant cry stimuli, which are as important as faces in child-rearing situations. Furthermore, scarce longitudinal evidence exists on how attentional bias toward infant crying changes through the postpartum period. Methods: In the present study, we conducted an experiment to assess bias toward infant crying at two postpartum time points: at Time 1 (Mean = 75.24 days), 45 first-time mothers participated and at Time 2 (Mean = 274.33 days), 30 mothers participated. At both time points, the mothers participated in a Stroop task with infant crying and white noise as the stimuli. They were instructed to answer the color out loud as quickly and accurately as possible, while ignoring the sound. Four types of audio stimuli were used in this task (the cry of the mother's own infant, the cry of an unfamiliar infant, white noise matched to the cry of the mother's own infant, and white noise matched to the cry of an unfamiliar infant), one of which was presented randomly before each trial. Response time and the correct response rate for each condition were the dependent variables. Results: For response time, the main effect of familiarity was significant, with longer response times when the participant's infant's cry was presented. In addition, response times were lower at Time 2 than at Time 1 in some conditions in which crying was presented. Discussion: The results suggest that mothers may be less disturbed by infant crying as they gain more experience. Elucidating the characteristics of postpartum mothers' changes in cognitive performance related to infants' cries would be useful in fundamental and applied research to understand the process of parents' adaptation to parenting.

Impact of visiting restrictions on Edinburgh postnatal depression scale screening scores at one month postpartum during the spread of COVID-19: a single-center case-control study in Japan.

BACKGROUND: This study aimed to evaluate whether "visiting restrictions" implemented due to the coronavirus disease 2019 (COVID-19) pandemic are a risk factor for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS). METHODS: This case-control study participants who gave birth during the spread of COVID-19 (COVID-19 study group) and before the spread of COVID-19 (control group). Participants completed the EPDS at 2 weeks and 1 month after childbirth. RESULTS: A total of 400 cases (200 in each group) were included in this study. The EPDS positivity rate was significantly lower with visiting restrictions than without (8.5% vs.18.5%, p = 0.002). Multivariate analysis of positive EPDS screening at the 1st month checkup as the objective variable revealed that visiting restrictions (odds ratio (OR): 0.35, 95% confidence interval (CI): 0.18-0.68), neonatal hospitalization (OR: 2.17, 95% CI: 1.08-4.35), and prolonged delivery (OR: 2.87, 95% CI: 1.20-6.85) were factors associated with an increased risk of positive EPDS screening. CONCLUSION: Visiting restrictions on family during the hospitalization period for delivery during the spread of COVID-19 pandemic did not worsen EPDS screening scores 1 month postpartum, but stabilized the mental state of some mothers.

Evaluation of calcification distribution by CT-based textural analysis for discrimination of immature teratoma.

BACKGROUND: Mature and immature teratomas are differentiated based on tumor markers and calcification or fat distribution. However, no study has objectively quantified the differences in calcification and fat distributions between these tumors. This study aimed to evaluate the diagnostic potential of CT-based textural analysis in differentiating between mature and immature teratomas in patients aged < 20 years. MATERIALS AND METHODS: Thirty-two patients with pathologically proven mature cystic (n = 28) and immature teratomas (n = 4) underwent transabdominal ultrasound and/or abdominal and pelvic CT before surgery. The diagnostic performance of CT for assessing imaging features, including subjective manual measurement and objective textural analysis of fat and calcification distributions in the tumors, was evaluated by two experienced readers. The histopathological results were used as the gold standard. The Mann-Whitney U test was used for statistical analysis. RESULTS: We evaluated 32 patients (mean age, 14.5 years; age range, 6-19 years). The mean maximum diameter and number of calcifications of immature teratomas were significantly larger than those of mature cystic teratomas (p < 0.01). The mean number of fats of immature teratomas was significantly larger than that of mature cystic teratomas (p < 0.01); however, no significant difference in the maximum diameter of fats was observed. CT textural features for calcification distribution in the tumors showed that mature cystic teratomas had higher homogeneity and energy than immature teratomas. However, immature teratomas showed higher correlation, entropy, and dissimilarity than mature cystic teratomas among features derived from the gray-level co-occurrence matrix (GLCM) (p < 0.05). No significant differences were observed in the CT features of fats derived from GLCM. CONCLUSION: Our results demonstrate that calcification distribution on CT is a potential diagnostic biomarker to discriminate mature from immature teratomas, thus enabling optimal therapeutic selection for patients aged < 20 years.

Attitudes toward cancer screening in regional Japan during the COVID-19 pandemic: An anonymous survey.

The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.

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.

YAP/TAZ-TEAD is a novel transcriptional regulator of genes encoding steroidogenic enzymes in rat granulosa cells and KGN cells.

Steroidogenesis in ovarian granulosa cells is regulated by the follicle-stimulating hormone (FSH) via transcriptional regulation of its related genes. We herein showed the involvement of the Hippo pathway in this regulation. In KGN granulosa cell, repression of YAP/TAZ activity induced the expression of CYP11A1, HSD3B2, and CYP19A1 in a TEAD-dependent manner without cAMP stimulation. A selective inhibitor of p38 MAP kinase, suppressed YAP/TAZ knockdown-indued the expression of these genes, suggesting this signal could be involved. The expression of these genes was induced by 8Br-cAMP, whereas that of CYR61 and ADATS1, typical YAP/TAZ-TEAD target genes, was suppressed, suggesting that the cellular signaling of cAMP reduced YAP/TAZ-TEAD activity. The constitutively active mutant YAP canceled the FSH- and 8Br-cAMP-mediated induction of these genes in primary rat granulosa and KGN cells, respectively. Moreover, regulation of steroidogenesis-related genes by YAP/TAZ-TEAD was independent of steroidogenic factor 1, a master gene regulator of steroidogenesis. These results suggest that YAP/TAZ-TEAD is a negative regulator of steroidogenesis and that suppression of YAP/TAZ-TEAD activity by FSH is involved in ovarian steroidogenesis.

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.

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.

Profiles of 5α-Reduced Androgens in Humans and Eels: 5α-Dihydrotestosterone and 11-Ketodihydrotestosterone Are Active Androgens Produced in Eel Gonads.

Although 11-ketotestosterone (11KT) and testosterone (T) are major androgens in both teleosts and humans, their 5α-reduced derivatives produced by steroid 5α-reductase (SRD5A/srd5a), i.e., 11-ketodihydrotestosterone (11KDHT) and 5α-dihydrotestosterone (DHT), remains poorly characterized, especially in teleosts. In this study, we compared the presence and production of DHT and 11KDHT in Japanese eels and humans. Plasma 11KT concentrations were similar in both male and female eels, whereas T levels were much higher in females. In accordance with the levels of their precursors, 11KDHT levels did not show sexual dimorphism, whereas DHT levels were much higher in females. It is noteworthy that plasma DHT levels in female eels were higher than those in men. In addition, plasma 11KDHT was undetectable in both sexes in humans, despite the presence of 11KT. Three srd5a genes (srd5a1, srd5a2a and srd5a2b) were cloned from eel gonads. All three srd5a genes were expressed in the ovary, whereas only both srd5a2 genes were expressed in the testis. Human SRD5A1 was expressed in testis, ovary and adrenal, whereas SRD5A2 was expressed only in testis. Human SRD5A1, SRD5A2 and both eel srd5a2 isoforms catalyzed the conversion of T and 11KT into DHT and 11KDHT, respectively, whereas only eel srd5a1 converted T into DHT. DHT and 11KDHT activated eel androgen receptor (ar)α-mediated transactivation as similar fashion to T and 11KT. In contrast, human AR and eel arß were activated by DHT and11KDHT more strongly than T and 11KT. These results indicate that in teleosts, DHT and 11KDHT may be important 5α-reduced androgens produced in the gonads. In contrast, DHT is the only major 5α-reduced androgens in healthy humans.

Mentality of pregnant women and obstetric healthcare workers about prenatal SARS-CoV-2 testing: A regional survey over the first wave of the COVID-19 pandemic in Japan.

AIM: To clarify the mentality of pregnant women and obstetric healthcare workers about prenatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing. METHODS: A multicenter questionnaire survey about prenatal SARS-CoV-2 screening testing was conducted among pregnant women, midwives and nurses (M&Ns), and obstetricians at all delivery facilities in Fukui Prefecture between June 30, 2020 and July 22, 2020. RESULTS: Of 297 pregnant women, 150 (50.5%) underwent prenatal polymerase chain reaction (PCR) testing, and 107 of them (71.3%) answered that because of prenatal PCR tests, they could give birth with relief. One hundred forty-five (48.8%) were concerned about the disadvantages of receiving positive prenatal PCR results. Of 287 M&Ns, 151 (52.6%) answered that prenatal PCR screening testing could reduce anxiety about infection to themselves; this belief was more common among M&Ns working at the nonreception facility than among those at COVID-19 reception facilities (60.7% vs. 47.1%, P = 0.02). Of 57 obstetricians, 31 (54.4%) agreed to prenatal SARS-CoV-2 PCR screening testing, the rate of which was significantly higher among obstetricians at nonreception facilities than those at reception facilities (70.3% vs. 25.0%, P < 0.01). Fourteen obstetricians (24.6%) were concerned about excessive medical treatment for asymptomatic pregnant women with false-positive PCR results. CONCLUSIONS: Pregnant women experience anxieties during the COVID-19 pandemic, and prenatal SARS-CoV-2 screening may reduce their anxiety to some extent. However, obstetrics staff at COVID-19 reception facilities are aware of the limits of prenatal screening and are concerned about excessive medical intervention due to false-positive results.

Bone morphogenetic protein-2 enhances gonadotropin-independent follicular development via sphingosine kinase 1.

PROBLEM: Pre-ovulatory mature follicles are not readily induced from gonadotropin (Gn)-independent early follicles in the poor ovarian response (POR) state, characterized by reduced number of retrieved oocytes. Bone morphogenetic protein (BMP), which is expressed in the ovary, contributes to early folliculogenesis, but its precise underlying mechanism remains unknown. The purpose of this study was to examine the effects of BMP-2 on granulosa cells (GCs) of Gn-independent early follicles. METHOD OF STUDY: Sphingosine kinase 1 (SPHK1) localization, which produces sphingosine 1-phosphate (S1P), was examined in human early follicles by immunohistochemistry. SPHK1 mRNA levels were examined in Gn-independent bovine GCs (bGCs) and human nonluteinized granulosa cell line (HGrC1) cells. Phosphorylated Yes-associated protein (YAP) expression was evaluated by Western blot, and its localization was evaluated immunocytochemically in bGCs. Verteporfin, a selective YAP inhibitor, was used to explore the influence of YAP on BMP-2-induced bGCs proliferation. RESULTS: The expression of SPHK1 was observed in human GCs of primary and secondary follicles. BMP-2 significantly induced SPHK1 mRNA expression in bGCs and HGrC1 cells. Both BMP-2 and S1P decreased phosphorylated YAP protein levels and induced the nuclear translocation of YAP significantly, thereby increasing the number of bGCs by suppressing the Hippo pathway. This BMP-2-induced cell proliferation was completely blocked by verteporfin. CONCLUSION: This is a first report showing that BMP-2 up-regulated SPHK1 mRNA expression in GCs and promoted GCs proliferation through Hippo pathway suppression. Thus, BMP-2 contributes to Gn-independent folliculogenesis via SPHK1, suggesting a potential therapeutic strategy for the POR patients with follicular dysgenesis.

Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer.

BACKGROUND: The mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin-dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients. METHODS: Expression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0-12. The expression scores calculated were correlated with clinicopathological parameters and patient survival. RESULTS: High immunoreactivity of phospho-Drp1Ser637 was significantly correlated with high-grade serous carcinoma (HGSC) (p = 0.034), residual postoperative tumor of > 1 cm (p = 0.006), and non-responders to adjuvant chemotherapy (p = 0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] (p = 0.011) and platinum-resistant recurrence (p = 0.030). ROC curve analysis showed that Drp1, phospho-Drp1Ser637 and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1Ser637 and CaMKI levels had significantly poorer progression free survival (PFS) (p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1Ser637 was significantly associated with PFS [p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039-9.561]. CONCLUSIONS: Drp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.

Inhibition of autophagy in theca cells induces CYP17A1 and PAI-1 expression via ROS/p38 and JNK signalling during the development of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a clinical syndrome characterized by hyperandrogenism, oligo/anovulation, and polycystic ovary. Autophagy is an intracellular system that degrades cytosolic proteins and organelles. The relationship between autophagy and PCOS has not been clarified. We found that p62 and ubiquitin were significantly increased in theca cells of women with PCOS using immunohistochemistry. Autophagy inhibition by palmitic acid and chloroquine in bovine theca cells increased p62 and ubiquitin and induced the expression of cytochrome P450 17A1 (CYP17A1) and plasminogen activator inhibitor-1 (PAI-1) mRNA. Furthermore, palmitic acid and chloroquine exposure significantly increased reactive oxygen species (ROS) and activated p38 and c-Jun N-terminal kinase (JNK). Inhibition of p38 and JNK significantly reduced CYP17A1 and PAI-1 mRNA expression. We showed that inhibition of autophagy in theca cells may have contributed to the pathogenesis of PCOS, based on CYP17A1 and PAI-1 mRNA expression via the ROS/p38 and JNK signalling pathways.