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.