This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Straszewski-Chavez, S. L. Articles by Mor, G. Search for Related Content PubMed PubMed Citation Articles by Straszewski-Chavez, S. L. Articles by Mor, G.

The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy

Department of Molecular, Cellular and Developmental Biology (S.L.S.-C.), Yale University, New Haven, Connecticut 06520; and Department of Obstetrics, Gynecology and Reproductive Sciences (V.M.A., G.M.), Yale University School of Medicine, New Haven, Connecticut 06520

Correspondence: Address all correspondence and requests for reprints to: Gil Mor, M.D., Ph.D., Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar Street FMB 301, New Haven, Connecticut 06520. E-mail: Gil.Mor{at}yale.edu

Apoptosis is important for normal placental development, but it may also be involved in the pathophysiology of pregnancy-related diseases. Normal placental development is dependent upon the differentiation and invasion of the trophoblast, the main cellular component of the placenta. Trophoblast apoptosis increases in normal placentas as gestation proceeds, and a greater incidence of trophoblast apoptosis has been observed in pregnancies complicated by preeclampsia or intrauterine growth retardation (IUGR). In response to different stimuli, apoptosis may be initiated extrinsically by the death receptor pathway or intrinsically by the mitochondrial pathway. The central executioners of apoptosis are the caspases, which cleave numerous vital cellular proteins to affect the apoptotic cascade. By inhibiting caspase activation, several endogenous inhibitors, including flice-like inhibitory proteins (FLIPs), inhibitors of apoptosis (IAPs), and antiapoptotic Bcl-2 family members, can prevent further propagation of the death signal. Macrophages present at the maternal-fetal interface may also contribute to trophoblast survival by removing apoptotic cells and producing cytokines and growth factors, which influence the progression of the apoptotic cascade. This review focuses on the role of apoptosis in trophoblast development and differentiation, the molecular mechanisms by which normal trophoblast apoptosis can occur, and how it is regulated to prevent excessive trophoblast apoptosis and possible pregnancy complications.

This article has been cited by other articles:

				A. MALAMITSI-PUCHNER, S. BAKA, M. BOUTSIKOU, S. LIOSI, D. GOURGIOTIS, E. PROTONOTARIOU, D. HASSIAKOS, and D. D. BRIANA Cord Blood Survivin Concentrations in Human Full-term Normal and Complicated Pregnancies In Vivo, January 1, 2009; 23(1): 139 - 142. [Abstract] [Full Text] [PDF]

				P. Laneve, U. Gioia, R. Ragno, F. Altieri, C. Di Franco, T. Santini, M. Arceci, I. Bozzoni, and E. Caffarelli The Tumor Marker Human Placental Protein 11 Is an Endoribonuclease J. Biol. Chem., December 12, 2008; 283(50): 34712 - 34719. [Abstract] [Full Text] [PDF]

				S.-Y. Oh, S.-J. Choi, Kyung Hee Kim, E. Cho, J.-H. Kim, and C.-R. Roh Autophagy-Related Proteins, LC3 and Beclin-1, in Placentas From Pregnancies Complicated by Preeclampsia Reproductive Sciences, November 1, 2008; 15(9): 912 - 920. [Abstract] [PDF]

				J. Detmar, M. Y. Rennie, K. J. Whiteley, D. Qu, Y. Taniuchi, X. Shang, R. F. Casper, S. L. Adamson, J. G. Sled, and A. Jurisicova Fetal growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and AhR-dependent changes in cell death Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E519 - E530. [Abstract] [Full Text] [PDF]

				D. A. Evseenko, P. Murthi, J. W. Paxton, G. Reid, B. S. Emerald, K. M. Mohankumar, P. E. Lobie, S. P. Brennecke, B. Kalionis, and J. A. Keelan The ABC transporter BCRP/ABCG2 is a placental survival factor, and its expression is reduced in idiopathic human fetal growth restriction FASEB J, November 1, 2007; 21(13): 3592 - 3605. [Abstract] [Full Text] [PDF]

				A.H. Taylor, C. Ang, S.C. Bell, and J.C. Konje The role of the endocannabinoid system in gametogenesis, implantation and early pregnancy Hum. Reprod. Update, September 1, 2007; 13(5): 501 - 513. [Abstract] [Full Text] [PDF]

				K. Koga and G. Mor Toll-like Receptors and Pregnancy Reproductive Sciences, May 1, 2007; 14(4): 297 - 299. [PDF]

				S. L. Straszewski-Chavez, I. P. Visintin, N. Karassina, G. Los, P. Liston, R. Halaban, A. Fadiel, and G. Mor XAF1 Mediates Tumor Necrosis Factor-{alpha}-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway J. Biol. Chem., April 27, 2007; 282(17): 13059 - 13072. [Abstract] [Full Text] [PDF]

				N. Bechi, F. Ietta, R. Romagnoli, S. Focardi, I. Corsi, C. Buffi, and L. Paulesu Estrogen-Like Response to p-Nonylphenol in Human First Trimester Placenta and BeWo Choriocarcinoma Cells Toxicol. Sci., September 1, 2006; 93(1): 75 - 81. [Abstract] [Full Text] [PDF]

				D. A. Evseenko, J. W. Paxton, and J. A. Keelan ABC drug transporter expression and functional activity in trophoblast-like cell lines and differentiating primary trophoblast Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1357 - R1365. [Abstract] [Full Text] [PDF]

				F. A. Hills, V. M. Abrahams, B. Gonzalez-Timon, J. Francis, B. Cloke, L. Hinkson, R. Rai, G. Mor, L. Regan, M. Sullivan, et al. Heparin prevents programmed cell death in human trophoblast Mol. Hum. Reprod., April 1, 2006; 12(4): 237 - 243. [Abstract] [Full Text] [PDF]