Apoptosis, or programmed cell death, is a natural mechanism by which the body eliminates unnecessary or potentially dangerous cells in order to maintain normal tissue function. During implantation, apoptosis is important for the appropriate tissue remodeling of the maternal decidua and invasion of the developing embryo [
7]. Although, first trimester trophoblasts are resistant to Fas-stimulation, apoptosis has been described in the trophoblast layer of placentas from uncomplicated pregnancies throughout gestation, suggesting that there is a constant cell turnover at the site of implantation necessary for the appropriate growth and function of the placenta [
21‐
23]. In addition, the incidence of trophoblast apoptosis is higher in third trimester villi compared to first trimester placenta [
24], suggesting that increasing placental apoptosis may be involved in the process of parturition. In pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR), there is a greater incidence of placental apoptosis in the first trimester, which is accompanied by insufficient trophoblast invasion [
23,
25]. Several mechanisms, in addition to apoptosis, have been described to limit extravillous trophoblast invasion into the uteroplacental arteries. These include reduced expression of integrin α1β1 [
26] decreased secretion of metalloproteinase (MMP-9) [
27] and low cell surface plasminogen activator activity, absent expression of vascular endothelial cadherin [
26] and reduced expression of HLA-G [
28]. The reduction of these factors, necessary for trophoblast differentiation and invasion is compatible with the hypothesis of increased apoptosis in IUGR because it is known that once the cells, including trophoblast, enter the apoptotic cascade this down regulate their level of transcription [
29]. This data suggests that the regulation of placental apoptosis is essential for the normal physiology of pregnancy.
However, cell death by apoptosis is not the end of the story, the clearance of apoptotic bodies represents a critical step in tissue homeostasis, preventing the release of intracellular contents, which may cause tissue damage and the possibility to initiate an inflammatory reaction.