Increased placental XIAP and caspase 3 is associated with increased placental apoptosis in a baboon model of maternal nutrient reduction.

Abstract

Our objective was to determine signaling molecules and apoptosis rate in the term placenta of a baboon model of maternal nutrient reduction (MNR). Female baboons were fed ad libitum for controls (n = 7) or 70% of control baboon diet (MNR; n = 6) from 30-165 days of gestation with necropsy at 165 days of gestation. Placental tissues were collected and fixed for immunohistochemistry or snap frozen to measure extracellular signal-regulated kinases, protein kinase B, JUN NH(2)-terminal kinase, X-linked inhibitor of apoptosis protein, and caspase 3. Placental villous apoptosis was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling and cytokeratin 18 cleavage. Compared with the control placentas, MNR placentas demonstrated reduced placental weight (P < .02), decreased phospho (p)-ERK (P < .04), increased placental villous apoptosis (P < .001), increased villous cytokeratin 18 cleavage, increased X-linked inhibitor of apoptosis protein (P < .007), and increased active caspase 3 (P < .02). We conclude that placental apoptosis is increased in this baboon model of MNR at term and that the increase in X-linked inhibitor of apoptosis protein may be a protective mechanism against this apoptosis.