Leptin and peroxisome proliferator-activated receptors: impact on normal and disturbed first trimester human pregnancy.

TY - JOUR

T1 - Leptin and peroxisome proliferator-activated receptors: impact on normal and disturbed first trimester human pregnancy.

AU - Toth, Bettina

AU - Bastug, Mehmet

AU - Scholz, Christoph

AU - Arck, Petra

AU - Schulze, Sandra

AU - Kunze, Susanne

AU - Friese, Klaus

AU - Jeschke, Udo

PY - 2008

Y1 - 2008

N2 - Recent in vitro and in vivo studies emphasize the impact of leptin, peroxisome proliferator-activated receptors (PPAR) and PPAR coactivators (retinoic X receptor a (RXR), amplified in breast cancer-3 gene (AIB3)) on placental and fetal development. Therefore, the frequency and distribution pattern of PPAR, RXR, AIB3 and leptin expression in normal human first trimester pregnancy, miscarriage and hydatidiform mole was investigated by immunohistochemistry and double immunofluorescence staining. Enhanced expression of PPAbeta/delta, RXR and AIB3 was identified in miscarried placentas. With regard to hydatidiform mole, increased expression of PPARgamma and PPARbeta/delta was observed, whereas RXR was significantly down-regulated. Leptin expression was lowest in miscarriage and highest in mole pregnancies. In contrast to trophoblast tissue, expression of leptin in glandular epithelial cells of the decidua was increased in miscarriage. PPAR and leptin expressing cells at the feto-maternal interface were identified as extravillous trophoblast (EVT) by double immunofluorescence and CK7 staining. In summary, significantly reduced leptin expression was accompanied by enhanced PPARbeta/delta, RXR and AIB3 expression in miscarried placentas. However, in mole pregnancy, up-regulation of leptin and increased expression of PPAR was detected. RXR, on the other hand, was down-regulated in mole decidua. So far, the study results implicate strong regulatory interaction of PPARs, their coactivators and leptin in human placentas. PPAR and leptin are potential targets for new treatment strategies concerning pregnancy disorders, such as miscarriage. The increasing knowledge about the role of PPARs and leptin in normal and disturbed pregnancy may help to improve pregnancy outcome.

AB - Recent in vitro and in vivo studies emphasize the impact of leptin, peroxisome proliferator-activated receptors (PPAR) and PPAR coactivators (retinoic X receptor a (RXR), amplified in breast cancer-3 gene (AIB3)) on placental and fetal development. Therefore, the frequency and distribution pattern of PPAR, RXR, AIB3 and leptin expression in normal human first trimester pregnancy, miscarriage and hydatidiform mole was investigated by immunohistochemistry and double immunofluorescence staining. Enhanced expression of PPAbeta/delta, RXR and AIB3 was identified in miscarried placentas. With regard to hydatidiform mole, increased expression of PPARgamma and PPARbeta/delta was observed, whereas RXR was significantly down-regulated. Leptin expression was lowest in miscarriage and highest in mole pregnancies. In contrast to trophoblast tissue, expression of leptin in glandular epithelial cells of the decidua was increased in miscarriage. PPAR and leptin expressing cells at the feto-maternal interface were identified as extravillous trophoblast (EVT) by double immunofluorescence and CK7 staining. In summary, significantly reduced leptin expression was accompanied by enhanced PPARbeta/delta, RXR and AIB3 expression in miscarried placentas. However, in mole pregnancy, up-regulation of leptin and increased expression of PPAR was detected. RXR, on the other hand, was down-regulated in mole decidua. So far, the study results implicate strong regulatory interaction of PPARs, their coactivators and leptin in human placentas. PPAR and leptin are potential targets for new treatment strategies concerning pregnancy disorders, such as miscarriage. The increasing knowledge about the role of PPARs and leptin in normal and disturbed pregnancy may help to improve pregnancy outcome.

M3 - SCORING: Zeitschriftenaufsatz

VL - 23

SP - 1465

EP - 1475

JO - HISTOL HISTOPATHOL

JF - HISTOL HISTOPATHOL

SN - 0213-3911

IS - 12

M1 - 12

ER -