Autophagy in Normal and Abnormal Early Human Pregnancies

Abstract

Autophagy is an inducible catabolic process by which cells degrade and recycle materials to survive stress, starvation, and hypoxia. The aim of this study was to evaluate autophagy at the fetal-maternal interface, to assess autophagy involvement during the early phase of human gestation, and to explore autophagic modification in case of early abnormal pregnancy outcome. Specimens were collected from first-trimester normal gestations undergoing legal termination of pregnancy and first-trimester sporadic spontaneous miscarriages. Autophagy was studied in villous and decidual samples by transmission electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. Autophagy markers were found in cytotrophoblast, syncytiotrophoblast, extravillous trophoblast, and decidual stromal cells. Autophagy is physiologically involved in early normal gestation. Compared with normal pregnancy, spontaneous miscarriage presents an increase in autophagy expression in villous specimens due to an increment in concentration of autophagic vacuole in syncytiotrophoblast, suggesting a cytoprotective mechanism of the cells to respond to microenvironmental challenge.

Evidence of Placental Autophagy during Early Pregnancy after Transfer of In Vitro Produced (IVP) Sheep Embryos

“…However, in both case, data were obtained from third trimester placenta while we focused on early development when a correct feto-maternal interaction is necessary for normal pregnancy proceeding. To our knowledge, there is only one study that reported an increased autophagy during early pregnancy in villous sample collected from spontaneous miscarriage [ 19 ]. However is not determined if autophagy has been induced as consequence of fetal demise, whereas in our study all analysed samples were collected from alive foetuses.…”

“…starvation, hypoxia) affecting both normal and complicated pregnancies. In human placentae, expression of autophagic marker has been detected throughout the normal gestation, from the early stage until delivery [ 17 – 19 ]. High autophagic activity was also reported in placentae (collected at delivery) from pregnancies complicated by IUGR [ 20 – 22 ] and pre-eclampsia [ 23 – 25 ], suggesting an important role for autophagy in normal and abnormal placentation.…”

Autophagy in the placenta

“…Recently, a study by Avagliano et al [91] demonstrated that enhanced expression of LC3-II in villous trophoblasts in spontaneous abortion with increased HIF-1α and cleaved caspase 3 in decidual tissue. Given the fact that the trophoblasts in human placenta have to adapt to the change in microenvironment at the maternal fetal interphase over nine months, gestational age-dependent change in placenta should not be underestimated.…”

Cell death and cell proliferation in human spina bifida

“…Immunofluorescence was performed as previously reported (Avagliano et al, , ; Pryor et al, ). Briefly, paraffin‐embedded 5‐µm tissue sections were deparaffinized in xylene and rehydrated through a graded series of alcohols.…”