Table I.
Selected Studies of Apoptosis in Spiral Artery Remodeling and in the Placental Pathologies, Pre-eclampsia, and Intrauterine Growth Restriction (IUGR)
| Author | Year | Tissue | Method | Main findings |
|---|---|---|---|---|
| IUGR | ||||
| Smith et al. | 1997 | Villous TB | IHC, EM | TUNEL staining demonstrates an increase in apoptosis in IUGR |
| Ishihara et al. | 2002 | Villous TB | IHC, EM | Increased TUNEL-positive nuclei in pre-eclampsia in both ST and CT. BcL-2 reduced in severe pre-eclampsia and IUGR. No difference in Fas |
| Levy et al. | 2002 | Villous TB | IHC | Increased TUNEL-positive nuclei in IUGR. Increased p53 in CT of IUGR but no difference in BcL-2 family proteins |
| Crocker et al. | 2003 | Villous TB | IHC | Enhanced apoptosis in IUGR and pre-eclampsia after treatment with 3%O2 or TNFa |
| Crocker et al. | 2004 | Villous TB | IHC | Increased apoptosis in placentas from women with pre-eclampsia or IUGR exposed to TNFa or 3%O2 |
| Daayana et al. | 2004 | Villous TB | Microscopy | Reduced syncytial area in IUGR. Reduction in syncytial/villous area ratio in pre-eclampsia but not in IUGR |
| Endo et al. | 2005 | Villous TB | IHC, EM | TUNEL staining and activated caspase-3 showed increased apoptosis in IUGR vs normal. No difference in p53 or Bax |
| Kadyrov et al. | 2006 | EVT | IHC | Severely impaired trophoblast invasion in pre-eclampsia and IUGR. Increased EVT apoptosis |
| Davy et al. | 2009 | Villous TB | Southern analysis | Increase in cell senescence regulators p21, p16, and EF-1 alpha in FGR placentas |
| Pre-eclampsia | ||||
| Difederico et al. | 1999 | EVT | IHC | 15–50% EVT apoptosis in pre-eclampsia, virtually zero in control. Lack of Bcl-2 staining in preeclamptic EVT |
| Allaire et al. | 2000 | Villous TB | IHC | Increased TUNEL-positive nuclei, increased Fas and reduced FasL in the villous TB of preeclamptic patients vs controls |
| Leung et al. | 2001 | Villous TB | EM, microscopy | Increased apoptosis in placentas from women with pre-eclampsia |
| Ishihara et al. | 2002 | Villous TB | IHC, EM | Increased TUNEL-positive nuclei in pre-eclampsia in both ST and CT. BcL-2 reduced in severe pre-eclampsia and IUGR. No difference in Fas |
| Crocker et al. | 2003 | Villous TB | IHC | Enhanced apoptosis in IUGR and pre-eclampsia after treatment with 3%O2 or TNFa |
| Crocker et al. | 2004 | Villous TB | IHC | Increased apoptosis in placentas from women with pre-eclampsia or IUGR exposed to TNFa or 3%O2 |
| Daayana et al. | 2004 | Villous TB | Microscopy | Reduced syncytial area in IUGR. Reduction in syncytial/villous area ratio in pre-eclampsia but not in IUGR |
| Heazell et al. | 2005 | Villous TB | IHC | Increased expression of p53 in ST nuclei and ST cytoplasm in placentas from women with pre-eclampsia. Reduction in Mdm2 in pre-eclampsia |
| Jeschke et al. | 2006 | Villous TB | IHC, IF | p53 and ki67 elevated in HELLP syndrome but not in pre-eclampsia. p53 reduced in CT from IUGR placentas, no effect upon proliferation |
| Kadyrov et al. | 2006 | EVT | IHC | Severely impaired trophoblast invasion in pre-eclampsia and IUGR. Increased EVT apoptosis |
| De Falco et al. | 2007 | Villous TB | IHC | p21 is expressed by CT and ST in pre-eclampsia |
| Cobellis et al. | 2007 | Villous TB | IHC | Increased Bax expression in miscarriage vs termination. Reduced Bax in Cesarean section vs normal birth. Also increased Bax in pre-eclampsia |
| Vascular remodelling | ||||
| Craven et al. | 1998 | EVT | IHC | Initial spiral artery changes, such as VCAM-1 expression and smooth muscle disruption are independent of trophoblast. |
| Difederico et al. | 1999 | EVT | IHC | 15–50% EVT apoptosis in pre-eclampsia, virtually zero in control. Lack of Bcl-2 staining in preeclamptic EVT |
| Dunk et al. | 2003 | EVT | IHC | EVTs penetrate the decidua and stimulate endothelial and smooth muscle disruption. Not seen in vessels cultured in the absence of EVT |
| Ashton et al. | 2005 | EVT | IHC, WB | Endothelial cells and VSMC express Fas and FasL. Trophoblast induced apoptosis in cultured endothelial cells |
| Kadyrov et al. | 2006 | EVT | IHC | Severely impaired trophoblast invasion in pre-eclampsia and IUGR. Increased EVT apoptosis |
| Smith et al. | 2009 | EVT | IHC | 4-stage model of trophoblast remodelling of spiral arteries. Transient role for uNK cells and macrophages in VSMC apoptosis |
ST, syncytiotrophoblast; CT, cytotrophoblast; EVT, extravillous trophoblast; FGR, fetal growth restricted; TB, trophoblast; VSMC, vascular smooth muscle cells; uNK, uterine natural killer.