[11beta-hydroxysteroid dehydrogenase type 2 enzyme activity effect after exposures phthalate esters in maternal].

OBJECTIVE: To study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development. METHODS: All of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11ß-HSD2 enzyme activity. RESULTS: MBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases) , 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11ß-HSD2 activity in case group ((THF+allo-THF)/THE = (0.79 ± 0.09) ng/ml) was significantly lower than that of the control group((THF+allo-THF)/THE = (0.58 ± 0.04) ng/ml); PAEs metabolites MBP (ß' = 1.12), MEHHP(ß' = 1.14), MEOHP(ß' = 1.10), SumDEHP(ß' = 1.08) in baby boy mother's urine was reversely correlated to 11ß-HSD2 activity. CONCLUSIONS: PAEs could affect fetal development by inhibit 11ß-HSD2 activity.

Postnatal hyperoxia or DEHP exposure leads to growth restriction and delayed lung development in newborn rats.

BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in many medical devices. We previously showed that maternal DEHP exposure led to restricted growth and delayed lung maturation in newborn rats. As oxygen toxicity continues to be a major risk factor for bronchopulmonary dysplasia, the aim of this study was to examine the effect of hyperoxia, DEHP or DEHP combined with hyperoxia on the growth and lung maturation of newborn rats. METHODS: Newborn rats received DEHP injection, hyperoxia exposure or DEHP injection combined with hyperoxia exposure for one week or two weeks. A control group received an equal volume of vehicle and was maintained in room air. RESULTS: Hyperoxia and hyperoxia + DEHP exposure for one week led to growth failure in newborn rats. Pups in the hyperoxia group showed catch-up growth after being maintained in room air for an additional 7 days but this was not the case with the latter group, which continued to receive DEHP. Hyperoxia and DEHP both delayed lung development, as evidenced by decreased radial alveolar count. Quantitative RT-PCR showed that hyperoxia decreased the transcripts of VEGF, VEGFR-2 and eNOS on days 7 and 14, and DEHP exposure alone also led to decreased expression of VEGF gene in 14-day-old rat pups. CONCLUSION: Postnatal hyperoxia and/or DEHP exposure lead to growth restriction and delayed lung alveolar development. The VEGF gene expression was altered and may be involved as one of the possible molecular mechanisms.