Investigating the regenerative effects of folic acid on human amniotic epithelial stem cells and amniotic pore culture technique (APCT) model in vitro using an integrated pharmacological-bioinformatic approach.

INTRODUCTION: Disruption of fetal membranes before the onset of labor is referred to as premature rupture of membranes (PROM). Lack of maternal folic acid (FA) supplementation reportedly leads to PROM. However, there is a lack of information on the location of FA receptors in the amniotic tissue. Additionally, the regulatory role and potential molecular targets of FA in PROM in vitro have rarely been investigated. METHODS: The three FA receptors (folate receptor α isoform [FRα], transporter of reduced folate [RFC], and proton-coupled folate transporter [PCFT]) in human amniotic epithelial stem cells (hAESCs) and amniotic tissue were localized using immunohistochemistry and immunocytochemistry staining. Effect and mechanism analyses of FA were performed in hAESCs and amniotic pore culture technique (APCT) models. An integrated pharmacological-bioinformatics approach was utilized to explore the potential targets of FA for the treatment of PROM. RESULTS: The three FA receptors were widely expressed in human amniotic tissue, especially in the hAESC cytoplasm. FA stimulated the amnion regeneration in the in vitro APCT model. This mimics the PROM status, in which cystathionine-ß-synthase, an FA metabolite enzyme, may play an important role. The top ten hub targets (STAT1, mTOR, PIK3R1, PTPN11, PDGFRB, ABL1, CXCR4, NFKB1, HDAC1, and HDAC2) of FA for preventing PROM were identified using an integrated pharmacological-bioinformatic approach. DISCUSSION: FRα, RFC, and PCFT are widely expressed in human amniotic tissue and hAESCs. FA aids the healing of ruptured membrane.

Influences of body size phenotype on the incidence of gestational diabetes needing prescription; analysis by Korea National Health Insurance (KNHI) claims and the National Health Screening Examination (NHSE) database.

OBJECTIVES: Although growing evidence has emphasized the pivotal role of metabolic status irrespective of body mass index (BMI), there has been no study to examine the association of body size phenotype with development of gestational diabetes that requires treatment with oral hypoglycemic agent or insulin (GDM+T) in primiparas. METHODS: Data from a total of 216,961 women who participated in the National Health Screening Examination (NHSE) between January 2007 and December 2011 and delivered their first babies within two years of the NHSE were analyzed. Body size phenotypes were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome according to the results of the NHSE. GDM+T was identified using the International Classification of Diseases-10th Revision (ICD-10) and prescription codes using Korea National Health Insurance (KNHI) claims. RESULTS: Approximately 0.39% of primiparas developed GDM+T. Compared to metabolically healthy normal weight (MHNW) women, both metabolically unhealthy normal weight (MUNW) and metabolically healthy obese (MHO) women had a significantly increased risk for developing GDM+T (odds ratio, OR: 9.53, 95% confidence interval, CI: 5.64-16.09 and OR: 3.30, 95% CI: 2.56-4.25, respectively). Specifically, MUNW individuals had a significantly higher risk of GDM+T when directly compared to MHO women even after adjusting for other GDM risk factors (OR: 2.92, 95% CI: 1.67-5.10). Furthermore, underweight women with metabolic syndrome showed a significantly increased frequency of GDM+T compared to MHNW subjects (OR: 8.87, 95% CI: 1.19-66.32). CONCLUSIONS: Pre-pregnant metabolic status is critical for development of GDM+T, regardless of their BMI. Therefore, intensive intervention for the components of metabolic syndrome may be helpful for the prevention of GDM+T even in low or normal weight women.

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.