Effects of prenatal ethanol exposure on rat brain radial glia and neuroblast migration.

Prenatal ethanol exposure (PEE) induces morphologic and functional alterations in the developing central nervous system. The orderly migration of neuroblasts is a key process in the development of a layered structure such as the cerebral cortex (CC). From initial stages of corticogenesis, the transcription factor Pax6 is intensely expressed in neuroepithelial and radial glia cells (RGCs) and is involved in continual regulation of cell surface properties responsible for both cellular identity and radial migration. In the present work, one month before mating, during pregnancy and lactation, a group of female Wistar rats were fed a liquid diet with 5.9% (w/w) ethanol (EtOH), rendering moderate blood EtOH concentrations. Maternal gestational weight progression and fetal CC thickness were measured. CC from E12-P3 rats were examined for expression of vimentin, nestin, S-100b, Pax6 and doublecortin using immunohistochemical assays. RGCs expressing vimentin, nestin, S-100b and Pax6 had abnormal morphologies. The migration distance through the CC and the number of doublecortin-ir neuroblasts in germinative zones were decreased. We found significant morphologic defects on RGCs, a marked delay in neuronal migration, decreased numbers of neuroblasts, and decreased numbers of Pax6-ir cells in the CC as a consequence of exposure to ethanol during development. These observations suggest a sequence of toxic events that contribute to cortical dysplasia in offspring exposed to EtOH during gestation.

Secretory and cytosolic phospholipase A2 activities and expression are regulated by oxytocin and estradiol during labor.

The release of arachidonic acid from membrane glycerophospholipids through the action of phospholipases (PLs) is the first step in the biosynthesis of prostaglandins (PGs). In reproductive tissues, the most important PLs are cytosolic PLA(2) (cPLA(2)) and types IIA and V of the secretory isoform (sPLA(2)). The aim of this work was to investigate the role of ovarian steroid hormones and oxytocin (OT) in the regulation of rat uterine PLA(2) activity and expression during pregnancy and labor. The activity of sPLA(2) increased near labor, whereas cPLA(2) activity augmented towards the end of gestation. The levels of sPLA(2) IIA and cPLA(2) mRNA showed an increase before labor (P<0.05, day 21), whereas sPLA(2) V mRNA was not regulated during pregnancy. The administration of atosiban (synthetic OT antagonist) together with tamoxifen (antagonist of estrogen receptors) was able to decrease cytosolic and secretory PLA(2) activities, diminish the expression of sPLA(2) IIA and cPLA(2), as well as decrease PGF(2 alpha) production before the onset of labor (P<0.01). The ovarian steroid did not affect PLA(2) during pregnancy. Collectively, these findings indicate that in the rat uterus, both 17beta-estradiol and OT could be regulating the activity and the expression of the secretory and the cytosolic isoforms of PLA(2), thus controlling PGF(2 alpha) synthesis prior to the onset of labor.