The ageing placenta and still birth (#275)
Back ground: Almost 1% of pregnancies end in still-birth, amounting to 2188 dead babies in Australia in 2008 (AIHW national perinatal statistic report, 2008), where the fetus is discovered to be dead, usually without warning and, in most cases without an identifiable cause. Globally, there are three million stillbirths each year.
Hypothesis: We propose the novel hypothesis that unexplained intrauterine death is related to placental aging.
Experimental Design: We have tried to compare biochemical sign of ageing between term and post-dated placentas.-We have collected placental tissues from normal term and post-dated (more than 41weeks) caesarean section. Some of placentas were frozen in liquid nitrogen for extraction of protein and some were fixed in paraformaldehyde for preparation of paraffin block.We have checked for sign of oxidative damage in protein and DNA in placental samples due to ageing. We also examined the length of telomere which is found to shorten due to ageing, in placentas by real time PCR. Additionally we have checked acetylation of histone-3 in placental samples by westernblot. We also investigated the accumulation of lysosome by specific marker lamp-2 and by immunohistochemistry in placental tissue sections.
Results: The Oxyblot showed that post-dated placentas (n=5) have higher levels of oxidised proteins than term placentas (n=5). We have also detected oxidised DNA by using an antibody against 8-hydroxy guanosine and fluorescent immunohistochemistry. Post-dated placentas showed higher DNA damage than term placentas. Real time PCR data showed that telomere lenghth is significantly shorter in post-dated (n=9) than term placentas (n=11). Additionally, we found that lysosome is accumulated in the basal part of syncitio-trophoblast and colocalized with mammalian target of rapamycin (mTOR) in post-dated placentas. The last phenomenon is very common to cellular ageing.
Conclusion: Overall our data showed considerable sign of ageing in post-dated placentas. We think that ageing placenta is unable provide to nutrition, gas and immunological support to growing fetus. This study may help us to provide an insight to unexplained stillbirth.