ҳ >>201409
ߣС ±԰ ¶ л л


ĿоҺڱࣨPAEsʴлˮƽ11-ǻ̴ø11-HSD2øԵĹ̽PAEsӰ̥ڷĿܻơ2012õȡڷٻIUGR33ƥ33øЧҺɫ-׷ⶨҺ4PAEsлڱᵥMBPڱᣨ2-һMEHPڱᣨ2-һ-5ǻ(MEHHP)ڱᣨ2-һ-5MEOHP3ƤʴƤͪлƤʴTHFallo-Ƥʴ(allo-THF)ƤͪTHEĺҺPAEsлˮƽ11-HSD2øԵĹ66ҺMBPMEHPMEHHPMEOHPлļʷֱΪ98%6589%5991%6091%60ĸҺMBPMEHHPMEOHPDEHPϼƣSumDEHPλֱΪ31.2024.6111.7248.67 ng/ml,ڶ飨ֱΪ17.3212.035.6828.64 ng/mlͳѧ壨Pֵ<0.05ĸ11-HSD2Ļԣ(THF+allo-THF)/THE=0.790.09 ng/mlݵڶ(THF+allo-THF)/THE=0.580.04 ng/mlݣӤĸҺMBP(¡=1.12)MEHHP(¡=1.14)MEOHP(¡=1.10)SumDEHP(¡=1.08)ĺ11-HSD2ĻԳʸأͳѧ壨Pֵ<0.05 PAEsͨ11-HSD2ĻӰ̥ڷ



ObjectiveTo study the association between phthalate esters (PAEs)  metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 211-HSD2 enzyme activity,  explore the possible mechanism of PAEs effect on fetal development. MethodsAll 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 urinemono-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 11-HSD2 enzyme activity. ResultsMBPMEHPMEHHPMEOHP metabolites can be detected in 98%65 cases,89%59 cases,91%60 cases,91%60 casesof all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP24.61 ng/ml for MEHHP11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control groupwere 17.32,12.03,5.68 and 28.64 ng/ml; 11-HSD2 activity in case group(THF+allo-THF)/THE=(0.790.09) ng/mlwas significantly lower than that of the control group((THF+allo-THF)/THE=(0.580.04) ng/ml);  PAEs metabolites MBP(¡=1.12),MEHHP(¡=1.14),MEOHP(¡=1.10),SumDEHP(¡=1.08) in baby boy mothers urine was reversely correlated to 11-HSD2 activity. ConclusionsPAEs could affect fetal development by inhibit 11-HSD2 activity.

Key words: Fetal growth retardationTetrahydrocortisolPhthalate esters;Intrauterine retarded;11ªhydroxy steroid dehydrogenase






1Ge RS, Chen GR, Tanrikut C, et al. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerationsJ. Reprod Toxicol, 2007, 23(3): 366373.
2Ma X, Lian QQ, Dong Q, et al. Environmental inhibitors of 11betahydroxysteroid dehydrogenase type 2J. Toxicology, 2011, 285(3): 8389.
3Heudorf U, MerschSundermann V, Angerer J,et al. Phthalates: toxicology and exposureJ. Int J Hyg Environ Health, 2007, 210(5): 623634.
4Foster PM. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate estersJ. Int J Androl, 2006, 29(1): 140147.
5Larsen ST, Hansen JS, Hansen EW, et al. Airway inflammation and adjuvant effect after repeated airborne exposures to di(2ethylhexyl) phthalate and ovalbumin in BALB/c miceJ. Toxicology, 2007, 235(1/2): 119129.
6Bility MT, Thompson JT, McKee RH, et al. Activation of mouse and human peroxisome proliferatoractivated receptors (PPARs) by phthalate monoestersJ. Toxicol Sci, 2004, 82(1): 170182.
7Zhang Y, Lin L, Cao Y, et al. Phthalate levels and low birth weight: a nested casecontrol study of Chinese newbornsJ. J Pediatr, 2009, 155(4): 500504.
8Benediktsson R, Lindsay RS, Noble J, et al. Glucocorticoid exposure in utero: new model for adult hypertensionJ. Lancet, 1993, 341(8841): 339341.
9Reinisch JM, Simon NG, Karow WG, et al. Prenatal exposure to prednisone in humans and animals retards intrauterine growthJ. Science, 1978, 202(4366): 436438.
10Hammer F, Stewart PM. Cortisol metabolism in hypertensionJ. Best Pract Res Clin Endocrinol Metab, 2006, 20(3): 337353.
11Shams M, Kilby MD, Somerset DA, et al. 11Betahydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restrictionJ. Hum Reprod, 1998, 13(4): 799804.
12Zhao B, Chu Y, Huang Y, et al. Structuredependent inhibition of human and rat 11betahydroxysteroid dehydrogenase 2 activities by phthalatesJ. Chem Biol Interact, 2010, 183(1): 7984.
13Hong D, Li XW, Lian QQ, et al. Mono(2ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11betahydroxysteroid dehydrogenase 2 in murine gonadotrope cellsJ. Biochem Biophys Res Commun, 2009, 389(2): 305309.
14Lin H, Lian QQ, Hu GX, et al. In utero and lactational exposures to diethylhexylphthalate affect two populations of Leydig cells in male LongEvans ratsJ. Biol Reprod, 2009, 80(5): 882888.
16ݳ. ڱ价ܼĴƷJ. ӡȾ2011281218.
17Koch HM, Calafat AM. Human body burdens of chemicals used in plastic manufactureJ. Philos Trans R Soc Lond B Biol Sci, 2009, 364(1526): 20632078.
18Hauser R, Meeker JD, Park S, et al. Temporal variability of urinary phthalate metabolite levels in men of reproductive ageJ. Environ Health Perspect, 2004, (112): 17341740.
19Zhang YH, Chen BH, Ding XC, et al. Reproductive and developmental toxicity in F1 SpragueDawley male rats exposed to dinbutyl phthalate in utero and during lactationJ. J Hyg Res. 2004, 33(1):914.
20ͣ±⣬֣. ƷڱĺJ.лԤҽѧ־2003,376429434.
22Hallmark N, Walker M,Mckinnell C, et al. Effects of monobutyl and di(nbutyl) phthalate in vitro on steroidogenesis and Leydig cell aggregation in fetal testis explants from the rat: comparison with effects in vivo in the fetal rat and neonatal marmoset and in vitro in the humanJ. Environ Health Perspect, 2007,115(3): 390396.

û 0

û ½ ע
  • 9
  • 3
  •  4 : ҳ:0/0ҳ 0¼ 5/ÿҳ
    | רҷ | Աע |
    ءַؽ69511 ʡࣺ100052
    Ȩ лҽѧἰлԤҽѧ־༭
    ICP 07035254