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Mol. Hum. Reprod. Advance Access originally published online on July 30, 2004
Molecular Human Reproduction 2004 10(9):665-669; doi:10.1093/molehr/gah091
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Molecular Human Reproduction vol. 10 no. 9 © European Society of Human Reproduction and Embryology 2004; all rights reserved

Effect of folic acid on homocysteine-induced trophoblast apoptosis

N. Di Simone1, P. Riccardi1, N. Maggiano2, A. Piacentani1, M. D'Asta1, A. Capelli2 and A. Caruso1,3

1Department of Obstetrics and Gynecology and 2Department of Pathology, Catholic University of Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy

3 To whom correspondence should be addressed. Email: acaruso{at}rm.unicatt.it

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 µmol/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.

Key words: apoptosis/folic acid/homocysteine/placenta/trophoblast


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