TY - JOUR
T1 - Effect of folic acid on homocysteine-induced trophoblast apoptosis
AU - Di Simone, Nicoletta
AU - Riccardi, Patrizia
AU - Maggiano, Nicola Giuseppe
AU - Piacentani, A.
AU - D'Asta, Marco
AU - Capelli, Arnaldo
AU - Caruso, Alessandro
PY - 2004
Y1 - 2004
N2 - In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 micromol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.
AB - In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 micromol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.
KW - effect of folic acid
KW - trophoblast apoptosis
KW - effect of folic acid
KW - trophoblast apoptosis
UR - http://hdl.handle.net/10807/21307
U2 - 10.1093/molehr/gah091
DO - 10.1093/molehr/gah091
M3 - Article
SN - 1360-9947
VL - 10
SP - 665
EP - 669
JO - Molecular Human Reproduction
JF - Molecular Human Reproduction
ER -