Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts†.

The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.

Manual vacuum aspiration for postpartum pyometra.

Postpartum pyometra is rare; however, it may lead to sepsis. The main initial symptoms are fever, lower abdominal pain and foul-smelling lochia. The treatment includes antibiotic administration and surgical drainage. This is a report of postpartum pyometra following a caesarean section that was successfully treated with manual vacuum aspiration, a simple and minimally invasive option. Other treatment options include pyometra reduction using placenta forceps and the placement of an intrauterine drainage catheter.

Optimized protocol for naive human pluripotent stem cell-derived trophoblast induction.

Human trophoblasts arise from the morula as trophectoderm, which differentiates into cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast after implantation. Here, we present a robust step-by-step protocol to induce trophectoderm (TE) from naive human pluripotent stem cells (PSCs) corresponding to pre-implantation epiblast. Our culture system (TE induction and ACE condition) mimics the entire trophoblast development including the molecular events. For complete details on the use and execution of this protocol, please refer to Io et al. (2021).

Capturing human trophoblast development with naive pluripotent stem cells in vitro.

Trophoblasts are extraembryonic cells that are essential for maintaining pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs), composing the placenta. Here we show that naïve, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naive PSC-derived TE and CTs (nCTs) recreated human and monkey TE-to-CT transition. nCTs self-renewed as CT stem cells and had the characteristics of proliferating villous CTs and CTs in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (BMP4, A83-01, and PD173074 [BAP]-treated primed PSCs [pBAPs]), pBAPs were distinct from nCTs and human placenta-derived CT stem cells, exhibiting properties consistent with the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naive human PSCs. Our system provides a platform to study the molecular mechanisms underlying trophoblast development and related diseases.

Severe fetal anemia as a consequence of extra-abdominal umbilical vein varix: A case report and review of the literature.

Umbilical vein varix is associated with a high incidence of fetal anomalies and perinatal complications. There are two types of umbilical vein varix: fetal intra-abdominal and extra-abdominal. Herein, a case is reported of severe fetal anemia with extra-abdominal umbilical vein varix. A 33-year-old primigravida was referred to our hospital for fetal growth restriction, fetal cardiomegaly, and decreased fetal movements at 26 weeks' gestation. A Doppler assessment showed an elevated middle cerebral artery peak systolic velocity at 2.2 MoM, suggesting fetal anemia. Umbilical vein varix had caused intermittent turbulent flow, provoking hemolytic anemia. Intrauterine transfusion improved fetal circulatory failure and anemia and prolonged gestational period. At 33 weeks' gestation, the patient underwent cesarean delivery due to nonreassuring fetal status. Pathological analysis revealed focal loss of vascular smooth muscle of the umbilical vein. Extra-abdominal umbilical vein varix has been reported in 14 cases including this case. The antenatal diagnosis rate is reported to be 79%; fetal heartbeat abnormalities and fetal deaths were reported as 50% and 14%, respectively. Eighty-six percent of patients had intra-umbilical cord thrombosis, but currently this is the only case of hemolytic anemia. Furthermore, extra-abdominal umbilical vein varix may present as fetal hydrops with anemia. During ultrasound examination of fetal anemia, umbilical cord screening should be performed with caution.

New era of trophoblast research: integrating morphological and molecular approaches.

Many pregnancy complications are the result of dysfunction in the placenta. The pathogenic mechanisms of placenta-mediated pregnancy complications, however, are unclear. Abnormal placental development in these conditions begins in the first trimester, but no symptoms are observed during this period. To elucidate effective preventative treatments, understanding the differentiation and development of human placenta is crucial. This review elucidates the uniqueness of the human placenta in early development from the aspect of structural characteristics and molecular markers. We summarise the morphogenesis of human placenta based on human specimens and then compile molecular markers that have been clarified by immunostaining and RNA-sequencing data across species. Relevant studies were identified using the PubMed database and Google Scholar search engines up to March 2020. All articles were independently screened for eligibility by the authors based on titles and abstracts. In particular, the authors carefully examined literature on human placentation. This review integrates the development of human placentation from morphological approaches in comparison with other species and provides new insights into trophoblast molecular markers. The morphological features of human early placentation are described in Carnegie stages (CS), from CS3 (floating blastocyst) to CS9 (emerging point of tertiary villi). Molecular markers are described for each type of trophoblast involved in human placental development. We summarise the character of human trophoblast cell lines and explain how long-term culture system of human cytotrophoblast, both monolayer and spheroid, established in recent studies allows for the generation of human trophoblast cell lines. Due to differences in developmental features among species, it is desirable to understand early placentation in humans. In addition, reliable molecular markers that reflect normal human trophoblast are needed to advance trophoblast research. In the clinical setting, these markers can be valuable means for morphologically and functionally assessing placenta-mediated pregnancy complications and provide early prediction and management of these diseases.

Placenta Accreta in a Woman with Childhood Uterine Irradiation: A Case Report and Literature Review.

The pregnancies of childhood cancer survivors who have received uterine irradiation are associated with a high risk of several obstetrical complications, including placenta accreta. The present case was a 26-year-old pregnant woman with a history of myelodysplastic syndrome treated with umbilical cord blood transplantation following chemotherapy and total body irradiation at the age of 10. Despite every possible measure to prevent preterm labor, uterine contractions became uncontrollable and a female infant weighing 892 g was vaginally delivered at 27+4 weeks of gestation. Under the postpartum ultrasonographic diagnosis of placenta accreta, we selected to leave the placenta in situ. Although emergency bilateral uterine artery embolization was required, complete resorption of the residual placenta was accomplished on the 115th day postpartum. Our experience highlighted the following points. (1) The expectant management of placenta accreta arising in an irradiated uterus may not only fulfill fertility preservation, but may also reduce possible risks associated with cesarean hysterectomy. (2) Due to extreme thinning of and a poor blood supply to the myometrium, reaching an antepartum diagnosis of placenta accreta in an irradiated uterus is difficult. (3) The recurrence of placenta accreta in subsequent pregnancies needs to be considered after successful preservation of the uterus.

Moyamoya Disease in Pregnancy: A 20-Year Single-Center Experience and Literature Review.

BACKGROUND: Pregnancy is a potential risk factor for stroke in women with Moyamoya disease. However, the rarity of the disease has limited clinical expertise to ensure a healthy pregnancy. The aim of the present study was to explore the possible risk factors for hemorrhagic and ischemic stroke in pregnant women with Moyamoya disease. METHODS: A retrospective review of cases in our hospital during a 20-year period and a review of the reported data were conducted to investigate pregnancy-related cerebrovascular events in women with Moyamoya disease. RESULTS: Thirty pregnancies in 20 women with Moyamoya disease were identified in the case review of our hospital. All were previously diagnosed cases, and no stroke had occurred during the study period. In the reported data review, pregnancy-related stroke in women with Moyamoya disease was identified in 54 (44 intracranial hemorrhage and 10 cerebral infarction). Intracranial hemorrhage occurred most commonly during the antepartum period (n = 39; 88.6%), with most events occurring at ≥24 weeks. Of the intracranial hemorrhage cases, 7 (15.9%) were complicated by hypertensive disorders of pregnancy, and 8 patients (18.2%) died of stroke. The onset of cerebral infarction was either in the antepartum (n = 4; 40.0%) or postpartum (n = 6; 60.0%) period. All postpartum cases occurred within 3-7 days after delivery. CONCLUSION: Pregnancy-related stroke in patients with Moyamoya disease might be susceptible to gestational age. Intracranial hemorrhage is prone to occur during the antepartum period, especially at ≥24 weeks, and cerebral infarction tends to occur postpartum.

An experience of second-trimester anhydramnios salvaged by single amnioinfusion.

Second-trimester anhydramnios, which is primarily caused by ruptured membranes, placental dysfunction, or congenital renal malformations, is associated with high perinatal morbidity and mortality. Although amnioinfusion temporarily increases amniotic fluid volume, it does not generally provide a fundamental solution. We describe a case of second-trimester anhydramnios with an umbilical cord factor, wherein single amnioinfusion may have successfully broken a vicious circle involving non-reassuring fetal status. A 34-year-old primigravid woman was referred to our hospital because of anhydramnios at 22 weeks' gestation. Single amnioinfusion improved the fetal circulatory failure, and the patient delivered a healthy full-term newborn. Single amnioinfusion may be a therapeutic approach to improve the prognosis of pregnancy when second-trimester anhydramnios results from umbilical cord factors.

Pneumocystis Pneumonia in Non-HIV Pregnant Women Receiving Chemotherapy for Malignant Lymphoma: Two Case Reports.

Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection that sometimes occurs in immunocompromised patients with human immunodeficiency virus (HIV). Here, we report two extremely rare cases of PCP in non-HIV pregnant women who underwent chemotherapy for malignant lymphoma. Case 1 is a 34-year-old primigravida who was diagnosed with Hodgkin's lymphoma. She received ABVD chemotherapy and developed PCP at 37 weeks of gestation. After the onset of PCP, emergent cesarean section was performed due to a nonreassuring fetal status. Case 2 is a 31-year-old multigravida with diffuse large B-cell lymphoma who was administered R-CHOP chemotherapy. At 34 weeks of gestation, she complained of dyspnea and developed PCP. She delivered her baby vaginally immediately after the onset of symptoms. Both patients were treated with sulfamethoxazole-trimethoprim (ST) and recovered shortly thereafter. The babies' courses were also uneventful. PCP remains a serious cause of death, especially in non-HIV patients, and, therefore, appropriate prophylaxis and a prompt diagnosis are imperative.

Vaginal delivery after placental abruption with intrauterine fetal death: A 20-year single-center experience.

AIM: The aim of this study was to elucidate the feasibility and safety of vaginal delivery (VD) when placental abruption causes fetal demise. METHODS: We conducted a retrospective study of women who were managed for placental abruption with intrauterine fetal death at Kyoto University Hospital during the period from 1995 to 2015. RESULTS: Sixteen cases were identified during the study period. VD was attempted in 15 cases and was accomplished in 14 (93.3%) cases. The median gestational age was 36 (24-39) weeks, and there were eight primiparas. The median Bishop score on admission was 2.5 (1-9). Eight pregnancies were complicated with pregnancy-induced hypertension. The median duration of labor was 5 h and 18 min (30 min-12 h 43 min), and the median amount of hemorrhage was 2503 (445-6808) mL. Fresh frozen plasma (≥ 20 U) and red cell concentrate (≥ 10 U) were administered in 10 (71%) and 9 (64%) cases, respectively. Two cases required uterine artery embolization for post-partum hemorrhage, while there was no case of maternal death or hysterectomy. Patients with Bishop score > 3 (n = 6) experienced shorter-duration deliveries (P = 0.020) and had significantly larger blood loss volume (P = 0.020) compared to patients with Bishop score ≤ 3. The duration of labor was negatively correlated with the amount of blood loss (R2 = -0.56, P = 0.039). CONCLUSION: After placental abruption with intrauterine fetal death, VD is feasible and safe regardless of gestational age, parity, cervical maturity, and duration of labor when intensive medical resources are available.

A Case of Ovarian Pregnancy Diagnosed by MRI.

Ovarian pregnancy is a rare form of ectopic pregnancy, causing a great diagnostic challenge. We report a case of ovarian pregnancy in a 42-year-old woman, in whom MRI successfully demonstrated the implantation in the ovary. Transvaginal ultrasonography showed an echogenic mass in the right ovary but failed to demonstrate tubal pregnancy. T2-weighted MR images disclosed a gestational sac structure in the right ovary, which exhibited heterogeneous high intensity intermingled with punctate foci of distinct low intensity. MRI may be a useful tool for diagnosing ovarian pregnancy, by demonstrating a gestational sac in the ovary.