Impaired cytotrophoblast cell-cell fusion is associated with reduced Syncytin and increased apoptosis in patients with placental dysfunction

• Published in: Molecular reproduction and development 2008-01, Vol.75 (1), p.175-183
• Main Authors: Langbein, Manuela, Strick, Reiner, Strissel, Pamela L., Vogt, Nicole, Parsch, Hans, Beckmann, Matthias W., Schild, Ralf L.
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis; Biological and medical sciences; Cell Fusion; cell-cell fusion; Cells, Cultured; Chorionic Gonadotropin, beta Subunit, Human - genetics; Chorionic Gonadotropin, beta Subunit, Human - metabolism; cytotrophoblast; Diseases of mother, fetus and pregnancy; Female; Fetal Growth Retardation - etiology; Fetal Growth Retardation - metabolism; Gene Expression; Gene Products, env - deficiency; Gene Products, env - genetics; Gynecology. Andrology. Obstetrics; HELLP Syndrome - metabolism; HELLP Syndrome - pathology; HELLP-syndrome; Humans; Medical sciences; Placenta - metabolism; Placenta - pathology; placentogenesis; Pre-Eclampsia - metabolism; Pre-Eclampsia - pathology; preeclampsia; Pregnancy; Pregnancy Proteins - deficiency; Pregnancy Proteins - genetics; Pregnancy. Fetus. Placenta; syncytin; Trophoblasts - metabolism; Trophoblasts - pathology
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.20729

Preeclampsia (PE), Hemolysis Elevated Liver Enzymes and Low Platelets (HELLP)‐syndrome, and intrauterine growth restriction (IUGR) are associated with abnormal placentation. In early pregnancy, placental cytotrophoblasts fuse and form multinuclear syncytiotrophoblasts. The envelope gene of the human endogenous retrovirus‐W, Syncytin, is a key factor for mediating cell–cell fusion of cytotrophoblasts. This study investigated clinical parameters of PE and HELLP‐associated IUGR and analyzed the cell–cell fusion index and β‐human chorionic gonadotropin (β‐hCG) secretion of cytotrophoblasts isolated and cultured from placentas of these patients. In addition, we performed absolute quantitation of Syncytin and determined the apoptosis rate in both cultured cytotrophoblasts and placental tissues. Cultured cytotrophoblasts from PE and HELLP‐associated IUGR correlated with a pronounced lower cell–cell fusion index, 1.8‐ and 3.6‐fold; less nuclei per syncytiotrophoblast, 1.4‐ and 2.0‐fold; a significantly decreased β‐hCG secretion, 4.3‐ and 17.2‐fold and a reduction of Syncytin gene expression, 8.1 (P = 0.019) and 222.7‐fold (P = 0.011) compared with controls, respectively. In contrast, a significantly 2.3‐fold higher apoptosis rate was observed in cultured PE/IUGR cytotrophoblasts (P = 0.043). Importantly, Syncytin gene expression in primary placental tissues of PE/IUGR was 5.4‐fold lower (P = 0.047) and in HELLP/IUGR 10.6‐fold lower (P = 0.019) along with a 1.8‐ and 1.9‐fold significant increase in the apoptosis rate compared with controls, respectively. Low Syncytin expression in both cultured cytotrophoblasts and primary tissues from pathological placentas supports an intrinsic placenta‐specific deregulation of cell–cell fusion in the formation of syncytiotrophoblasts leading to increased apoptosis. These processes could contribute to the development and severity of PE and HELLP‐associated IUGR. Mol. Reprod. Dev. 75: 175–183, 2008. © 2007 Wiley‐Liss, Inc.