D-chiro-inositol phosphoglycan expression in human placenta at term in diabetes

Abstract

We present a histological assessment of diabetic placenta for the localization of some insulin mediators that were reported to play a major role for lipid/glycogen metabolism in human placenta. Placental metabolism is fundamental to fetal wellbeing. In fact, all maternal metabolic alterations have a profound effect on placental development with a subsequent definite impact on pregnancy outcome and fetal growth [1]. We have previously reported abnormalities in expression and activation of specific insulin-like growth factor-I receptor signaling molecules and multiple members of the MAP kinase family in human placentas of fetuses with intra-uterine growth restriction [2]. Subsequent studies on placental metabolism have focused on a family of insulin mediators, namely inositol phosphoglycans that were found to be highly expressed in diabetic and preeclamptic placentas [3]. These molecules play a major role in the regulation of the disposal of glucose by oxidative and non-oxidative routes of storage by glycogen synthesis [4]. In fact, the complexity and specificity of insulin action are determined by an integrated signaling network of independent intracellular pathways with several downstream effectors that have been shown to modulate the signal amplitude and frequency for both shortand longterm effects. Specific acquired alterations in activation of proteins involved in insulin signaling in preeclamptic placenta were shown to be associated with the accumulation of D-chiro-inositol phosphoglycan and to play a role in the insulin-resistant state that occurs in preeclampsia [5]. A disturbed insulin signaling was demonstrated in these cases and associated to low activation of insulin receptor effectors through multiple serine phosphorylations in both IRS-1 and IRS-2 [5]. In this study, placental specimens from six healthy and diabetic women at term were assessed for chiro-inositol using antibodies (mouse anti-D-chiro-inositol phosphoglycan), kindly provided by Professor Eduardo Martinez (Pamplona, Spain). A standard procedure was used for the immunohistochemical staining. The primary anti-D-chiroinositol phosphoglycan antibody was diluted 1:100 in antibody diluent (Dako, USA) and incubated for 60 min at room temperature. The percentage of positive stained controls was used as a reference for comparison. In control cases (Fig. 1a), a clear immunostaining of the syncytiotrophoblast was found (p = 0.11) with a little activity within the villous stroma (p = 0.43). The endothelium of placental vessels shows a localization of D-chiro-inositol phosphoglycan in normal placenta while in diabetic samples is weakly stained (p \ 0.01, Fig. 1b). The extravillous trophoblast in the basal plate of diabetic cases reveals also staining (p = 0.23, Fig. 1c, d). In both cases, a weak staining was found in maternal plasma, while a strong staining was found in fetal plasma. According to these findings, we may hypothesize that the placenta uptakes D-chiro inositol phosphoglycan from M. Scioscia (&) Department of Obstetrics and Gynecology, Sacro Cuore Don Calabria General Hospital, Via Don A. Sempreboni, 5, 37024 Negrar, VR, Italy e-mail: marco.scioscia@sacrocuore.it