MicroRNA­155­5p inhibits trophoblast cell proliferation and invasion by disrupting centrosomal function.

Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently observed in recurrent miscarriage. Several microRNAs (miRs), including miR­155­5p, are aberrantly upregulated in recurrent miscarriage; however, the underlying molecular mechanisms remain unclear. The centrosome orchestrates microtubule networks and coordinates cell cycle progression. In addition, it is a base for primary cilia, which are antenna­like organelles that coordinate signaling during development and growth. Thus, deficiencies in centrosomal functions can lead to several disease, such as breast cancer and microcephaly. In the present study, the signaling cascades were analyzed by western blotting, and the centrosome and primary cilia were observed and analyzed by immunofluorescence staining. The results showed that overexpression of miR­155­5p induced centrosome amplification and blocked primary cilia formation in trophoblast cells. Notably, centrosome amplification inhibited trophoblast cell growth by upregulating apoptotic cleaved­caspase 3 and cleaved­poly (ADP­ribose) polymerase in miR­155­5p­overexpressing trophoblast cells. In addition, overexpression of miR­155­5p inhibited primary cilia formation, thereby inhibiting epithelial­mesenchymal transition and trophoblast cell invasion. All phenotypes could be rescued when cells were co­transfected with the miR­155­5p inhibitor, thus supporting the role of miR­155­5p in centrosomal functions. It was also found that miR­155­5p activated autophagy, whereas disruption of autophagy via the depletion of autophagy­related 16­like 1 alleviated miR­155­5p­induced apoptosis and restored trophoblast cell invasion. In conclusion, the present study indicated a novel role of miR­55­5p in mediating centrosomal function in recurrent miscarriage.

PDGF-AA activates AKT and ERK signaling for testicular interstitial Leydig cell growth via primary cilia.

Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual characteristics. Type A platelet-derived growth factor (PDGF-AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF-AA or its congenital receptor PDGFR-α leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF-AA/PDGFR-α signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR-α are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF-AA/PDGFR-α signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF-AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF-AA-activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF-AA/PDGFR-α signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.

A de novo partial trisomy 9p with Dandy-Walker malformation and ventriculomegaly.

OBJECTIVE: We present a female neonate with de novo trisomy 9p24.3-q21.2 presented with a neurological anomaly. CASE REPORT: Her birth length was 41 cm (<3rd percentile), birth body weight was 1600 g (<5th percentile), and head circumference was 29.5 cm (<5th percentile). She had low-set ears, deep and wide-set eyes with downslanting palpebral fissures, and a full nasal bridge with a globular nose. In addition, a rocker bottom foot was noted after further evaluation. Congenital heart anomalies, including patent ductus arteriosus (0.43 cm), large atrial septal defect, and malalignment ventricular septal defect (0.64 cm) were also confirmed. Brain magnetic resonance imaging showed partial agenesis of the cerebellum and corpus callosum. Furthermore, severe bilateral communicating hydrocephalus was found. CTG-banded chromosome analysis revealed 47, XX, +mar. CONCLUSION: DNA analysis may be mandatory for small gene segments. In trisomy 9p, we proposed further delineation of the critical region correlating to neurological malformations.

Prophylactic Intraoperative Uterine Artery Embolization During Cesarean Section or Cesarean Hysterectomy in Patients with Abnormal Placentation: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effectiveness and safety of prophylactic intraoperative uterine artery embolization (UAE) performed immediately after fetal delivery during planned cesarean section or cesarean hysterectomy in patients with placenta accreta spectrum disorder or placenta previa. METHODS: A systematic search was conducted on Ovid MEDLINE and Embase, PubMed, Web of Science, and Cochrane databases. Studies were selected using the Population/Intervention/Comparison/Outcomes (PICO) strategy. The intraoperative blood loss and the rate of emergent peripartum hysterectomy (EPH) were the primary outcomes, whereas the length of hospital stay and volume of blood transfused were the secondary outcomes. A random-effects model was employed to pool each effect size. The cumulative values of the primary outcomes were calculated using the generic inverse variance method. RESULTS: Eleven retrospective cohort studies and five case series were included, recruiting 421 women who underwent prophylactic intraoperative UAE (UAE group) and 374 women who did not (control group). Compared with the control group, the UAE group had significantly reduced intraoperative blood loss (p = 0.020) during cesarean section or cesarean hysterectomy. Furthermore, the EPH rate was also significantly decreased (p = 0.020; cumulative rate: 19.65%), but not the length of hospital stay (p = 0.850) and volume of pRBC transfused (p = 0.140), after cesarean section in the UAE group. The incidence of major complications was low (3.33%), despite two patients with uterine necrosis. CONCLUSION: The currently available data provides encouraging evidence that prophylactic intraoperative UAE may contribute to hemorrhage control and fertility preservation in women with abnormal placentation. REGISTRATION: PROSPERO registration code: CRD42021230581. https://clinicaltrials.gov/ct2/show/CRD42021230581 LEVEL OF EVIDENCE: Level 2a, systematic review of retrospective cohort studies.

Sesamin inhibits cervical cancer cell proliferation by promoting p53/PTEN-mediated apoptosis.

Background: Sesamin is a major bioactive compound in sesame seeds and has various biological properties, including anti-inflammatory and anticancer activities. Here, we explored whether sesamin activates p53, which is widely inhibited in cervical cancer cells, thereby inducing p53-mediated apoptosis. Methods: Human HeLa and SiHa cervical cancer cells and normal Hs68 dermal cells were used as cell models. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by the CCK-8 assay and flow cytometry using PI/Annexin V staining, respectively. Protein expression and phosphorylation were determined using western blotting. The involvement of p53 in the apoptotic cascade was assessed by a specific inhibitor. Results: Sesamin (75 and 150 µM) clearly inhibited SiHa and HeLa cell proliferation in a dose-dependent fashion, but did not affect the proliferation of Hs68 cells. Meanwhile, sesamin increased the sub-G1 phase ratio and apoptosis, up to approximately 38.5% and 37.8%, respectively. Furthermore, sesamin induced p53 phosphorylation at serine-46 and serine-15 and upregulated the levels of PUMA, Bax, and PTEN, while inhibiting AKT phosphorylation at serine-473. Inhibition of p53 by pifithrin-α significantly reduced the levels of PUMA, Bax, and PTEN but restored AKT phosphorylation in SiHa cells exposed to sesamin. Pifithrin-α also reduced apoptosis and restored the proliferation of HeLa and SiHa cells exposed to sesamin. Conclusions: These findings indicate that sesamin inhibits cervical cancer cell proliferation, and its mechanism may be attributed to the induction of p53/PTEN-mediated apoptosis. This suggests that sesamin might be useful as an adjuvant in promoting anti-cervical cancer treatments.

Acute abdomen in early pregnancy due to ovarian torsion following successful in vitro fertilization treatment.

OBJECTIVE: Ovarian torsion is an acute abdomen requiring prompt intervention. Ovarian torsion seldom occurs during pregnancy. However, with in vitro fertilization (IVF) treatments, ovarian hyperstimulation may increase the size of the ovaries and result in the occurrence of adnexal torsion. Here, we report two cases of ovarian torsion after IVF and discuss the optimal management of this emergency medical condition. CASE REPORT: The first case was a 23-year-old woman who received IVF-embryo transfer due to tubal factor infertility. Sudden-onset, lower abdominal pain developed at the 6th week of pregnancy. Conservative treatment with antibiotics was the initial approach, but a right oophorectomy had to be performed due to right ovarian torsion with hemorrhagic and gangrenous changes. The second case was a 38-year-old woman diagnosed with bilateral ovarian torsion at 8 weeks' gestation due to the sudden onset of low abdominal pain. Laparoscopy was arranged immediately after the diagnosis was confirmed. The left ovary was successfully preserved due to prompt intervention. Both pregnancies continued without problems after surgery. CONCLUSION: Ovarian hyperstimulation during IVF-embryo transfer treatment is a risk factor for developing adnexal torsion. Early diagnosis and prompt surgical intervention is the only way to protect the ovary and preserve the pregnancy. Laparoscopic surgery in early pregnancy causes no harm to the fetus and should be encouraged once the diagnosis is confirmed. Delaying surgery may induce serious infection and jeopardize the lives of both the fetus and mother.

Multidisciplinary examination for prenatal diagnosis of posterior cervical teratoma in early second trimester.

OBJECTIVE: Cervical teratomas represent approximately 3% of all congenital teratomas, which occur in approximately 1 in 20,000-40,000 live births. In this report, we present a case of congenital posterior cervical teratoma diagnosed by a two-dimensional (2D) ultrasound in the early second trimester. CASE REPORT: A 28-year-old woman, gravid 1, para 0, came to our prenatal clinic at 20 weeks of gestation for her first prenatal visit. Results of an ultrasound revealed a fetus with multiple cystic septal mass with internally calcified spots measuring approximately 3 cm over the left fetal neck. Because no other abnormality was noted at that time, magnetic resonance imaging (MRI) and amniocentesis were scheduled on the following day. At the same time, results of a 4D ultrasound revealed the mass size to be same as that measured by the 2D ultrasound; however, the location was defined on the left posterior neck and MRI showed there was no invasion to the intracranial area. The parents opted to continue the pregnancy. In the following prenatal cares, no polyhydramnios was found and the fetal body weight was within the normal growth curve. The baby was delivered by cesarean section at 38 weeks of gestation with Apgar scores of 8 (at 1 minute) and 9 (at 5 minutes). The baby was scheduled for surgical intervention 3 days after birth. Finally, results of a pathological analysis revealed the mass to be a benign cystic teratoma. CONCLUSION: Prenatal diagnosis of cervical teratoma is very crucial, allowing early detection of masses that obstruct the airway. Therefore, a multidisciplinary examination and follow-up are recommended for early prenatal diagnosis.