Adrenomedullin antagonist treatment during early gestation in rats causes fetoplacental growth restriction through apoptosis

Biology of Reproduction
Josthna PenchalaneniChandrasekhar Yallampalli

Abstract

Adrenomedullin (AM), a potent vasorelaxant peptide, has been shown to function as an angiogenic and growth factor. The present study investigated whether antagonism of endogenous AM in rats during early gestation results in diminished placental and fetal growth and whether this occurs through induction of apoptosis. Rats on Gestational Day 8 were implanted s.c. with osmotic minipumps delivering 125 and 250 microg rat(-1) day(-1) of AM(22-52) and were killed on Gestational Day 15. In AM(22-52)-treated rats, both placental and fetal weights were dose-dependently inhibited, with 50% reduction in the group receiving 250 microg rat(-1) day(-1). In these animals, fetal resorption sites were also increased. Apoptosis was demonstrated in placenta and uterus by the TUNEL method. Apoptotic changes were more apparent in trophoblast cells in the labyrinth zone of placenta and uterine decidua of AM(22-52)-treated rats when compared with vehicle-control rats. Immunoreactivity to active caspase-3 protein was abundant in the placenta and uterus of the AM(22-52)-treated group. Western blot analysis demonstrated that in homogenates of both the placenta and uterus of AM(22-52)-treated rats, levels of active caspase-9 and -3 as well as of Poly ADP...Continue Reading

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Citations

Sep 19, 2006·The Journal of Clinical Investigation·Manyu LiKathleen M Caron
Jul 16, 2013·Reproductive Biology and Endocrinology : RB&E·Ken-Go HayashiToru Takahashi
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Apr 9, 2014·Autonomic Neuroscience : Basic & Clinical·Rafik HachaniKamel Kacem
Jul 26, 2014·Biology of Reproduction·Haijun GaoChandra Yallampalli

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Methods Mentioned

BETA
light microscopy

Software Mentioned

SigmaGel

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