Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia.

An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-ß and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-ß, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-ß, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-ß, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia.

A Case of Nager Syndrome Diagnosed Before Birth.

Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly.

Successful Delivery after Abdominal Radical Trachelectomy, Using Transabdominal Cerclage in Early Pregnancy.

Radical trachelectomy (RT) is a fertility-sparing surgery for cervical cancer. Postoperative pregnancies have a high risk of abortion and prematurity. To prevent this, a procedure involving transabdominal cerclage (TAC) was devised for shortened cervical canals post-RT. Here we describe the successful management of a pregnancy after abdominal RT (ART). The 34-year-old patient was gravida 1, para 0. When she was 27, she underwent ART for stage Ib1 cervical cancer, and she became pregnant 7 years later. Because her cervical canal was 16.7 mm during early pregnancy, we performed TAC at 12 weeks of pregnancy. Post-surgery, we administered an infusion of ritodrine hydrochloride for tocolysis. A selective caesarean section was performed at 36 weeks, with the delivery of a healthy infant.

Upregulation of Angiogenic Factors via Protein Kinase C and Hypoxia-induced Factor-1α Pathways under High-glucose Conditions in the Placenta.

Abnormal glucose metabolism during pregnancy is an established risk factor for preeclampsia (PE). Disruption of the balance between placental angiogenic factors is linked to PE pathophysiology. We examined whether hypoxia-induced factor-1α (HIF-1α) and protein kinase Cß (PKCß) are involved in the regulation of placental angiogenic factors under high-glucose conditions in vitro. The human choriocarcinoma cell lines BeWo and JEG-3, and the human trophoblast cell line HTR-8/SVneo were cultured with 10 and 25 mmol/L glucose [control glucose group (CG) and high-glucose group (HG), respectively]. We examined the changes in HIF-1α, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) expression in the CG and HG by real-time PCR and ELISA. PKC activation was also measured by ELISA. The expressions of HIF-1α, sFlt-1, PlGF, and VEGF were significantly higher in the HG than in the CG. PKC activity was significantly increased in the HG. High glucose affected the expression of angiogenic factors in choriocarcinoma cells via the PKCß and HIF-1α pathways, suggesting their involvement in PE pathogenesis.

Comparison of Kidney Function between Gestational Hypertension and Preeclampsia.

Although gestational hypertension (GH) is thought to be different from preeclampsia (PE), in Japan GH and PE are usually treated as the same disease (i.e., pregnancy-induced hypertension). Here we sought to determine whether there are any differences in fetal growth and maternal kidney function between pregnancies with PE and those with GH. We retrospectively analyzed 61 GH patients and 60 PE patients with singleton pregnancies who delivered at Okayama University Hospital (2008-2015). We compared maternal and perinatal outcomes and maternal kidney function parameters between the GH and PE pregnancies. The mean values of maternal age (p=0.01), gestational age at delivery (p<0.0001), placental weight (p=0.002), birth weight and height (p<0.0001, p=0.0001), and head circumference standard deviation score (p=0.007) of newborns of the GH group were significantly higher than those of the PE group. The duration until termination of PE or GH was not significantly correlated with kidney function. The birth weight percentile was significantly correlated with kidney function in PE but not GH. However, GH patients with poor kidney function and small-for-gestational age infants showed perinatal outcomes similar to those of the PE group. Monitoring kidney function is thus important for determining the severity of PE and GH.

Successful pregnancy located in a uterine cesarean scar: A case report.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Because CSP carries a high risk of uterine rupture and life-threatening bleeding, the pregnancy should be terminated upon confirmation of diagnosis. There have been few reports of CSP with successful delivery. We present a case of CSP under expectant management, with delivery via planned cesarean section at 35 weeks of gestation. This report suggests that successful pregnancy outcome can be achieved in some women with uterine cesarean scar, but further analysis and additional studies are required in order to describe the optimal protocol of expectant management in CSP.

Sex differences in early growth during the first three years of life in offspring from mothers with pregnancy-induced hypertension.

OBJECTIVES: Newborns born to mothers with pregnancy-induced hypertension (PIH) are thought to be at high risk for lifestyle-related diseases, such as obesity and hypertension, in adulthood. STUDY DESIGN: A longitudinal study of 78 pregnant women with PIH and their newborns, who visited Okayama University Hospital from 2009 to 2013. MAIN OUTCOME MEASURES: We investigated the change in growth of offspring born to mothers with PIH and compared it with the standard growth curve in Japanese to examine whether there was rapid catch-up growth during the first 3years of life. RESULTS: Subjects were 78 pregnant women with PIH and their offspring, who visited Okayama University Hospital from 2009 to 2013. Valid responses were obtained from 29 of 78 (37.1%) women. Body weight and length at birth were at the third percentile or less in females, and at the 10th percentile or less, in males. When body weight and length were compared at 6months, 18months, and 3years old between male and female toddlers, male toddlers slowly caught up until 3years old, but female toddlers rapidly caught up in the first 6months. Furthermore, in newborns with fetal growth restriction caused by the intrauterine environment of PIH, differences in physical development between male and female toddlers were more remarkable. CONCLUSIONS: There is a significant sex difference in catch-up growth during the first 3years, which might be involved in lifestyle-related diseases in adulthood, suggesting continuous follow-up is necessary, especially for female offspring.

The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters.

Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.