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

Abstract

Objective: Our objective was to determine signaling molecules and apoptosis rate in the term placenta of a baboon model of maternal nutrient reduction (MNR).

Study design: 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.

Results: 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).

Conclusion: 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.

Figure 1

Fetal and placental weights in fetuses of control and maternal nutrient reduction (MNR) groups at 165 days of gestation

Figure 2

Apoptosis demonstrated by Tunnel staining in A) placenta of a control ad libitum fed mother and B) placenta of a nutrient restricted mother. Quantification of percent apoptotic cells between groups (C).

Figure 3

Cytokeratin 18 cleavage (M30) in placenta of control and MNR animals. Cytokeratin 7 immunofluorescence (red) in the baboon placenta (A). Placental sections for neg control (B), control ad libitum fed mother (C), and maternal nutrient reduction group (D).

Figure 4

Placental villi XIAP protein from the control ad libitum fed and maternal nutrient reduction groups. Characteristic western blot of CIAP (A) and the corresponding densitometry quantification (B)

Figure 5

Placental villi active caspase 3 protein from control ad libitum fed and maternal nutrient reduction groups. Panel A shows a characteristic western blot, and panel B reflects the corresponding densitometry quantification.

Figure 6

Characteristic western blots and protein quantification for ERK (A), AKT (B) and JNK (C) in placental villi from control ad libitum fed and maternal nutrient reduction groups.