Min Jeong Oh

Vitamin D deficiency in gestational diabetes mellitus and the role of the placenta

OBJECTIVE The aim of this study was to evaluate the relationships between maternal vitamin D levels and gestational diabetes mellitus (GDM) and differences in the placental production of vitamin D receptor (VDR), CYP24A, and CYP27B1. STUDY DESIGN Forty normal pregnant women and 20 women with GDM were included in this study. Serum levels of 25-hydroxyvitamin D (25[OH]D) were measured with enzyme-linked immunosorbent assay. The expression and production of VDR, CYP27B1, and CYP24A1 in the placenta were evaluated with real time-polymerase chain reaction and Western blot, respectively. RESULTS We found that 27.5% of normal pregnant women and 85% of women with GDM had vitamin D deficiency, with serum 25(OH)D levels <20 ng/mL. Serum levels of 25(OH)D were lower in women with GDM than normal pregnant women (P < .01). The production of CYP24A1 protein and messenger RNA expression was significantly higher in placental tissue from patients with GDM than in those from normal pregnancies; however, the production of CYP27B1 and VDR protein and messenger RNA expression were not different between 2 the groups. CONCLUSION In this study, vitamin D deficiency was associated with GDM. Given that 25(OH)D is hydroxylated by CYP27B1 to the bioactive 1,25(OH)2D form, and CYP24A1 catabolizes both 25(OH)D and 1,25(OH)2D to the inactive metabolites, respectively, our data indicate that the elevated activity of CYP24A1 in the placenta may play a key role in the development of vitamin D deficiency in GDM.

Cytokine expression in placenta-derived mesenchymal stem cells in patients with pre-eclampsia and normal pregnancies

OBJECTIVES The aim of this study was to investigate the levels of cytokines in placenta-derived mesenchymal stem cells (MSCs) in normal pregnancies and those with pre-eclampsia. MATERIALS AND METHODS C5a, CD40 Ligand, G-CSF, GM-CSF, GROalpha, I-309, sICAM-1, IFN-gamma, IL-1alpha, IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-16, IL-17, IL-17E, IL-23, IL-27, IL-32alpha, IP-10, I-TAC, MCP-1, MIF, MIP-1alpha, MIP-1beta, Serpin E1, RANTES, SDF-1, TNFalpha, and sTREM-1 were measured in mesenchymal stem cells using the human cytokine array panel A. The soluble intracellular adhesion molecule-1 (sICAM-1), stromal-derived factor-1 (SDF-1) and monocyte chemotactic protein-1 (MCP-1) were measured by real-time PCR and confirmed by Western blot analysis. RESULTS MSCs derived from the deciduas of normal pregnancies had significantly elevated levels of sICAM (p=0.000) and SDF-1 (p=0.011), compared to the pregnancies with pre-eclampsia. The level of MCP-1 in the decidua-derived MSCs was not significantly different. No significant difference was observed between normal and pre-eclamptic pregnancies for the amnion-derived MSCs. CONCLUSIONS The decreased levels of sICAM and SDF-1 found in the decidua-derived MSCs from pre-eclamptic pregnancies might be associated with some of the immunological alterations in pre-eclampsia.

Role of Estrogen Receptor-α and -β) in Regulating Leptin Expression in 3T3-L1 Adipocytes

We investigated the effects of the estrogen receptor‐α (ERα) and ‐β (ERβ) in the regulation of leptin, resistin, and adiponectin expression in 3T3‐L1 adipocytes. Mature adipocytes were exposed to estradiol (E2), ERα agonist (PPT (4,4′,4″‐(4‐propyl‐[1H]‐pyrazole‐1,3,5‐triyl)trisphenol)), ERβ agonist (DPN (2,3‐bis(4‐Hydroxyphenyl)‐propionitrile)), E2 with ERα antagonist (MPP (1,3‐Bis(4‐hydroxyphenyl)‐4‐methyl‐5‐[4‐(2‐piperidinylethoxy)phenol]‐1H‐pyrazole dihydrochloride)), and E2 with ERβ antagonist (R, R‐THC ((R, R)‐5,11‐diethyl‐5,6,11,12‐tetrahydro‐2,8‐chrysenediol)) at different concentrations. To clarify the expression and regulation of adipokines by ER subtypes, total RNA was extracted from cells and measured using quantitative PCR. Western blot analysis was performed to evaluate the protein expression of adipokines, ERα, and ERβ. The leptin expression was significantly increased in the cells treated with high concentrations (10−5 and 10−6 mol/l) of the PPT (P < 0.01, P < 0.05). By contrast, the leptin expression decreased in a dose‐dependent manner in the MPP‐treated groups (P < 0.05). High concentrations (10−5 mol/l) of R, R‐THC with E2 (10−7 mol/l) caused a significant increase of the leptin expression (P < 0.01). The leptin mRNA levels were positively correlated with the ERα mRNA levels (r = 0.584, P < 0.01) and negatively correlated with the ERβ mRNA levels (r = −0.236, P = 0.03) in the adipocytes. The ratio of the ERα to ERβ mRNA levels in the adipocytes was significantly associated with leptin mRNA levels (r = 0.454, P < 0.01). ERα induced leptin expression and ERβ inhibited its expression in 3T3‐L1 adipocytes. The ratio of the ERα‐to‐ERβ expression in 3T3‐L1 adipocytes may be an important potential regulatory factor in leptin expression.

Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes.

Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes.

Correlations between umbilical and maternal serum resistin levels and neonatal birth weight

Objective. Resistin is a novel hormone secreted by human adipocytes and mononuclear cells. It is expressed in the human placenta, and has been postulated to play a role in the regulation of energy metabolism during pregnancy. However, correlations between umbilical and maternal serum resistin levels and neonatal birth weight remain poorly understood. The purpose of the study was to clarify the correlation between umbilical cord and maternal serum resistin levels and neonatal birth weight. Materials and methods. This study included 37 healthy mothers, neonates. Resistin levels were determined by ELISA, and compared for correlation between umbilical cord and maternal serum resistin levels and neonatal birth weight. Results. The ranges of resistin levels for umbilical and maternal sera were 10.61–40.81 and 1.14–25.54 ng/ml, respectively. Mean umbilical serum resistin level (21.34±1.07 ng/ml) was significantly higher than maternal serum resistin level (10.13±1.12) (p<0.001). Umbilical serum resistin levels were positively correlated with maternal serum resistin levels (r=0.607, p<0.001) and negatively with neonatal birth weight (r= − 0.345, p=0.037). No significant differences in resistin levels were discovered between the female and male neonates. In addition, there were no correlation between the umbilical resistin levels and maternal body mass indices, umbilical leptin levels, or insulin levels. Conclusions. It is suggested that resistin not only affects energy homeostasis by existing in high levels in the fetus, but may play an important role in controlling body weight through effective regulation of adipogenesis by negative feedback.

High-risk human papillomavirus infection is associated with premature rupture of membranes

BackgroundHuman papillomavirus (HPV) is known to be more prevalent in spontaneous abortions than in elective terminations of pregnancy. More recently, placental infection with HPV was shown to be associated with spontaneous preterm delivery. However, no study has evaluated the prevalence of HPV infection in pregnant Korean females and its association with adverse pregnancy outcomes.MethodsWe conducted a cross-sectional study of 311 females who gave birth at Korea University Medical Center. Our sample included 45 preterm deliveries, 50 cases of premature rupture of the membranes (PROM), 21 preeclampsia cases, and 8 gestational diabetes mellitus (GDM) patients. We used the Hybrid Capture II system to detect high-risk (HR)-HPV infection at six weeks postpartum.ResultsThe prevalence of HR-HPV infection was 14.1%. Women with HR-HPV infection had a higher incidence of PROM than those without HR-HPV. HR-HPV infection was associated with an increased risk of PROM (OR, 2.380; 95% CI, 1.103-5.134). The prevalence of preterm delivery, preeclampsia, or GDM was not different between the two groups.ConclusionsWe observed a high prevalence of HR-HPV infection in pregnant women. Moreover, HR-HPV infection was associated with a risk of PROM at term. Further studies are needed to evaluate mechanisms by which HR-HPV infection induces PROM.

Serum levels of YKL-40 and interleukin-18 and their relationship to disease severity in patients with preeclampsia

Preeclampsia is a disease associated with the maternal inflammatory response. YKL-40 and interleukin-18 (IL-18) are inflammatory markers involved in inflammatory states and vascular processes. The aim of this study was to evaluate serum levels of YKL-40 and IL-18 in preeclampsia. Twenty-four patients with preeclampsia and 13 healthy pregnant women were included in this study. Serum levels of YKL-40 and IL-18 were measured using an enzyme-linked immunosorbent assay (ELISA). Serum YKL-40 levels were significantly higher in patients with preeclampsia (median 75.0 ng/mL; range 45.8-125.4 ng/mL) than in normal pregnant women (median 29.3 ng/mL; range 16.2-39.5 ng/mL; p=0.000). Serum IL-18 levels were also significantly higher in patients with preeclampsia (median 159.9 pg/mL; range 125.6-193.5 pg/mL) than in normal pregnant women (median 120.2 pg/mL; range 102.2-157.9 pg/mL; p=0.018). Notably, higher serum YKL-40 levels were observed in patients with more severe proteinuria (>or=3+ by dipstick) than in patients with milder proteinuria (<or=1+ by dipstick; median 121.3 ng/mL, range 63.5-146.7 ng/mL versus median 55.4 ng/mL, range 29.4-116.3 ng/mL; p=0.022). There was, however, no significant difference in serum IL-18 levels between patients with more severe proteinuria and those with milder proteinuria. We conclude that circulating YKL-40 and IL-18 are elevated in patients with preeclampsia, and levels of YKL-40 are related to the severity of the disease.

Prophylactic Hypogastric Artery Ballooning in a Patient with Complete Placenta Previa and Increta

Abnormal attachment of the placenta (Placenta accreta, increta, and percreta) is an uncommon but potentially lethal cause of maternal mortality from massive postpartum hemorrhage. A 33-yr-old woman, who had been diagnosed with a placenta previa, was referred at 30 weeks gestation. On ultrasound, a complete type of placenta previa and multiple intraplacental lacunae, suggestive of placenta accreta, were noted. For further evaluation of the placenta, pelvis MRI was performed and revealed findings suspicious of a placenta increta. An elective cesarean delivery and subsequent hysterectomy were planned for the patient at 38 weeks gestation. On the day of delivery, endovascular catheters for balloon occlusion were placed within the hypogastric arteries, prior to the cesarean section. In the operating room, immediately after the delivery of the baby, bilateral hypogastric arteries were occluded by inflation of the balloons in the catheters previously placed within. With the placenta retained within the uterus, a total hysterectomy was performed in the usual fashion. The occluding balloons were deflated after closure of the vaginal cuff with hemostasis. The patient had stable vital signs and normal laboratory findings during the recovery period; she was discharged six days after delivery without complications. The final pathology confirmed a placenta increta.

Accessory breast tissue presenting as a vulvar mass in an adolescent girl

BackgroundThe development of an accessory breast tissue is attributed to the failure of regression of milk line remnants during embryogenesis. The accessory breasts can develop anywhere along the milk line, extending from axilla to the groin. The vulvar accessory breast is extremely rare among these.CaseWe report an 18-year-old girl presenting a solitary vulvar mass which is later pathologically confirmed to be an accessory breast tissue. On preoperative ultrasonographic examination, a lobulated echogenic mass with internal septa was seen in the subcutaneous fat layer of the mons pubis. Excisional biopsy was performed, which revealed an accessory breast tissue. She had no specific developmental abnormalities and had no familial history.ConclusionAn accessory breast in the vulva is an extremely rare case among the ectopic breasts, especially in an adolescent girl. Pathological confirmation is mandatory in this case to exclude a possibility of other tumor, including malignancy.

Secular Trends of Gestational Diabetes Mellitus and Changes in Its Risk Factors

Objective The aim of this study was to evaluate the secular trends of incidence of gestational diabetes mellitus (GDM) and insulin treatment for GDM in a Korean population and to determine the factors that contribute to the trends in the incidence of GDM. Study Design We used data collected by the Health Insurance Review & Assessment Service of Korea and analyzed data from women who had given birth from 2006 to 2010. We evaluated the trends in the incidence of GDM and GDM requiring insulin treatment and the changes in risk factors. Results There were 1,824,913 births during the study period, which included 129,666 cases of GDM, an incidence of 7.11% over this period. The incidence of GDM increased from 3.86% in 2007 to 11.83% in 2010, with a continuous increase after adjustment for age. However, the number of GDM cases that required insulin treatment decreased significantly from 13.87% in 2007 to 5.94% in 2010. The proportion of patients who were at an older age and multiparity, 2 GDM risk factors, increased during the study period. Conclusions In Korea, the incidence of GDM, especially mild GDM, increased dramatically during the period from 2006 to 2010. Further efforts are needed to monitor this trend and to identify associated factors.