Hornocysteine induces trophoblast cell death with apoptotic features
Hornocysteine induces trophoblast cell death with apoptotic features
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DOI：
10.1095/biolreprod.103.015800
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Caruso, A
中科院分区：
文献类型：
--
作者：
Di Simone, N;Maggiano, N;Caruso, A
高同型半胱氨酸血症已被认为是习惯性流产、胎盘早剥或梗死、先兆子痫和/或宫内生长迟缓妇女的一个可能的危险因素。然而，对同型半胱氨酸作用的致病机制知之甚少。本研究探讨了同型半胱氨酸在体外影响滋养细胞促性腺激素分泌和诱导细胞死亡的能力。在原代人滋养细胞中，同型半胱氨酸处理（20 μ mol/L）导致细胞变平和增大，假足延伸和细胞空泡化。细胞脱离、凋亡和坏死是有利的。通过原位缺口末端标记，我们研究了DNA降解，并使用M30 CytoDEATH对凋亡细胞的细胞质进行选择性染色。研究了细胞色素c从线粒体向细胞质溶胶的释放和琼脂糖凝胶中DNA的裂解。同型半胱氨酸，而非半胱氨酸，诱导滋养细胞凋亡并显著减少人绒毛膜促性腺激素的分泌。这些发现提示滋养细胞死亡可能是同型半胱氨酸引起胎盘疾病相关妊娠并发症的致病机制。
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 mumol/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.