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Homocysteine Induces Trophoblast Cell Death with Apoptotic Features¹

Department of Obstetrics and Gynecology³ Department of Histology,⁴ Catholic University of Sacred Heart, 00168 Rome, Italy

Hyperhomocysteinemia has been suggested as a possible risk factor in women suffering from habitual abortions, placental abruption or infarcts, preeclampsia, and/or intrauterine growth retardation. However, little is known about the pathogenic mechanisms underlying the action of homocysteine. The present study investigated the in vitro ability of homocysteine to affect trophoblast gonadotropin secretion and to induce cell death. In primary human trophoblast cells, homocysteine treatment (20 µmol/L) resulted in cellular flattening and enlargement, extension of pseudopodia, and cellular vacuolization. Cellular detachment, apoptosis, and necrosis were favored. With in situ nick end labeling, we investigated DNA degradation, and we used M30 CytoDEATH to selectively stain the cytoplasm of apoptotic cells. Cytochrome c release from mitochondria to the cytosol and DNA cleavage in agarose gel have been investigated. Homocysteine, but not cysteine, induced trophoblast apoptosis and significantly reduced human chorionic gonadotropin secretion. These findings suggest that trophoblast cell death might represent a pathogenic mechanism by which homocysteine may cause pregnancy complications related to placental diseases.

¹ Supported in part by research grants from the Catholic University of Rome (D1, year 2001) and by Farmades S.p.A. Pharmaceutical Industries (Rome, Italy).

² Correspondence: Alessandro Caruso, Department Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy. FAX: 39 6 35510031; acaruso{at}katamail.com

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