Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&A are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan.

The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of phase I and phase II drug-metabolizing enzymes, as well as members of the drug transporter family, including multiple drug resistance (MDR) 1, which has a major role in multidrug resistance. Previously, we have demonstrated that steroid/xenobiotics metabolism by tumor tissue through the PXR-cytochrome P-450 3A (CYP3A) pathway might play an important role in endometrial cancer. In this study, we examined which endocrine-disrupting chemicals (EDCs) and anticancer agents might be ligands for PXR and whether these chemicals enhanced PXR-mediated transcription through two different PXR-responsive elements (PXREs), CYP3A4 and MDR1, in endometrial cancer cell lines. Some steroids/EDCs strongly activated PXR-mediated transcription through the CYP3A4-responsive element compared with the MDR1-responsive element, whereas these steroids/EDCs also enhanced the CYP3A4 expression compared with the MDR1 expression. In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. We also analyzed how these ligands regulated PXR-mediated transcription through two different PXREs. In the presence of PXR ligands, there was no difference in the DNA binding affinity of the PXR/retinoid X receptor heterodimer to each PXRE, but there were different interactions of the coactivator to each PXR/PXRE complex. These data suggested that PXR ligands enhanced PXR-mediated transcription in a ligand- and promoter-dependent fashion, which in turn differentially regulated the expression of individual PXR targets, especially CYP3A4 and MDR1.

Objective Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5 < body mass index < 25) or overweight.Design A cross-sectional study of 110 pregnant Japanese women who visited the Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan.Setting Tertiary referral centre serving 2000 births.Methods Serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng), adiponectin and leptin were measured in women with pre-eclampsia and in normotensive controls matched for age, gestational week, parity and body mass index.Main outcome measures Serum levels of sFlt-1, PlGF, the sFlt-1/ PlGF ratio, sEng, adiponectin and leptin.Results The sFlt-1/PlGF ratio in early-onset pre-eclampsia was significantly higher than that in late-onset pre-eclampsia (112.0 ± 30.2 versus 45.4 ± 43.8, P = 0.037). There was a significant elevation of leptin in both subtypes relative to controls (early: 58.6 ± 18.3 ng/ml versus 26.0 ± 6.7 ng/ml, P = 0.001; late: 39.5 ± 9.2 ng/ml versus 22.0 ± 4.3 ng/ml, P = 0.005), but adiponectin was increased only in late-onset pre-eclampsia (36.5 ± 13.4 lg/ml versus 12.0 ± 4.3 lg/ml, P = 0.003). Significant differences in angiogenic factors and adiponectin were found between normal and overweight women only in late-onset pre-eclampsia.Conclusions These data suggest that there are different profiles of angiogenic factors and adipocytokines between women who develop early-and late-onset pre-eclampsia.

Estrogen has been shown to contribute greatly to growth and development in endometrial cancer. And recent research has suggested that intratumoral production of estrogen may play important roles in this cancer tissue. On the other hand, pregnane X receptor (PXR), a new member of nuclear receptors, has been shown to mediate the genomic effects of steroid hormones, including estrogen and xenobiotics. And this receptor is thought to regulate the expression of the cytochrome P-450 3A (CYP3A) gene family, which plays important roles in the metabolism of endogenous steroids and xenobiotics. Various levels of PXR expression were found in endometrial cancer tissues but not normal tissues. Tissues showing high PXR expression showed significantly high expression of CYP3A4/7 and low expression of estrogen receptor (ER) compared with levels in tissues showing low PXR expression. In endometrial cancer cell lines, HEC-1 cells, which express high PXR and low ER and progesterone receptor, show a stronger transcriptional response of the PXR-CYP3A pathway to the PXR ligands, especially endocrine-disrupting chemical, than do Ishikawa cells. These data suggest that the steroid/xenobiotics metabolism in the tumor tissue through PXR-CYP3A pathway might play an important role, especially in alternative pathway for gonadal hormone and endocrine-disrupting chemical effects on endometrial cancer expressing low ER alpha.

No abstract

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of drug-metabolizing enzymes, cytochrome P450 3A (CYP3A) family, and members of the drug transporter family, including multiple drug resistance 1 (MDR1). We demonstrated previously that steroid/xenobiotic metabolism by tumor tissue through the PXR-CYP3A pathway might play an important role in endometrial cancer and that PXR ligands enhance PXRmediated transcription in a ligand-and promoter-dependent fashion, leading to differential regulation of individual PXR targets, especially CYP3A4 and MDR1. In this study, we investigated the potential contribution of PXR down-regulation by RNA interference toward the augmentation of drug sensitivity and the overcoming of drug resistance. We observed the protein levels of both CYP3A4 and MDR1 in PXR small interfering RNA (siRNA)-transfected cells were not increased in the presence of PXR ligands, paclitaxel, cisplatin, estradiol, or medroxyprogesterone acetate (MPA) compared with control siRNA-transfected cells. There was no PXR-mediated transactivation or augmentation of transcription by coactivators in the presence of these ligands. We then found that PXR downregulation caused a significant increase in cell growth inhibition and enhancement of apoptosis in the presence of the anticancer agents, paclitaxel, cisplatin, and MPA. Finally, we demonstrated that PXR overexpression caused a significant decrease in cell growth inhibition and inhibited apoptosis in the presence of paclitaxel or cisplatin. These data suggest that PXR downregulation could be a novel therapeutic approach for the augmentation of sensitivity to anticancer agents, or to overcome resistance to them, in the treatment of endometrial cancer.Pregnane X receptor (PXR), a new member of the steroid receptor superfamily, has been shown to mediate the genomic effects of several steroid hormones, including progesterone, pregnenolone, and estrogen, and those of xenobiotics, and to bind to specific DNA sequences, PXR-responsive elements (PXREs) in the mouse, rat, and human (Kliewer et al

We propose that the primary tumor's SUVmax obtained from F-FDG PET/CT may be associated with aggressive biological characteristics in endometrial cancer.