*3.1. Cell Injury and Apoptosis*

Several studies have shown that placental tissues obtained from women with high-resistance uterine artery Doppler indices were more sensitive to apoptotic stimuli than placental tissue from women with normal indices [8–10]. Charolidi et al. examined the e ffect of tumor necrosis factor alpha (TNF α) on placental endothelial cell (PEC) apoptosis in the context of high vs. normal uterine artery Dopplers (Figure 1). They demonstrated that placental endothelial cells (PECs) from the high resistance index (RI) group exposed to TNF α had a 40% reduction in half-life compared to those from the normal RI group which were exposed to TNF α [10].

**Figure 1.** Apoptosis of first-trimester placental endothelial cells (PEC) from normal (normal RI) and high-resistance (high-RI) pregnancies in response to stimulation with TNFα and actinomycin D. First-trimester PEC were cultured with 30 ng/mL TNFα and 800 ng/mL actinomycin D. Images were taken every 15 min over 15 h. (**a**) The kinetics of the induction of apoptosis for PEC, high RI (n = 8 mean ± SEM, black symbols) and normal RI (n = 8 mean ± SEM, grey symbols). (**b**) In a separate cohort, normal-RI PEC were incubated with TNFα and actinomycin D alone (n = 4), as well as in the presence of the broad-spectrum caspase inhibitor, zVAD-fmk (n = 4). The results are expressed as mean ± SEM and \* p < 0.05. Adapted with permission from Charolidi et al. [9].
