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. 2008 Jul;199(1):80.e1-8.
doi: 10.1016/j.ajog.2007.12.017. Epub 2008 Mar 4.

Decreased placental X-linked inhibitor of apoptosis protein in an ovine model of intrauterine growth restriction

Juan A Arroyo  1 , Russell V Anthony, Henry L Galan
Affiliations

Decreased placental X-linked inhibitor of apoptosis protein in an ovine model of intrauterine growth restriction

Juan A Arroyo et al. Am J Obstet Gynecol. 2008 Jul.

Abstract

Objective: The objective of the study was to assess placental apoptosis at both midgestation and near term in an ovine model of placental insufficiency (PI) and intrauterine growth restriction (IUGR).

Study design: At 40 days' gestational age (dGA), 2 groups of 4 ewes were exposed to hyperthermic conditions for either 55 days or 80 days to induce IUGR with necropsies at 95 (midgestation) and 130 dGA (term = 140 dGA), respectively. Blood gases were assessed and placental tissues obtained for apoptosis analyses.

Results: PI-IUGR pregnancies showed: (1) a decrease in fetal O(2) saturation and pO(2) (P < .04), (2) an increase in placental villi apoptosis (P < .05) at midgestation and near term, and (3) a decrease of cotyledon X-linked inhibitor of apoptosis protein (XIAP) at both gestational periods (P < .04) with no differences in caruncle XIAP protein.

Conclusion: Placental villous apoptosis is increased at midgestation and near term in our ovine model of IUGR, and this increase is associated with a significant decrease in XIAP protein in the cotyledon of IUGR animals.

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Figures

Figure 1
Figure 1
Fetal and placental weights at mid-gestation and near-term. A significant decrease in placental weight was observed in IUGR animals at both stages of pregnancy while fetal weight was significantly deceased only near-term.
Figure 2
Figure 2
Apoptosis at mid-gestation and near-term placentae. A significant increase (4-fold) in apoptosis was observed at mid-gestation in the placental villi of IUGR sheep (A). Apoptosis was increased (2.4-fold) near-term in the IUGR sheep placental villi (B). White arrows indicate TUNEL positive cells.
Figure 3
Figure 3
Mid-gestation cotyledon DNA degradation. A higher degree of DNA degradation was observed in the cotyledon of IUGR animals vs. controls.
Figure 4
Figure 4
Cytokeratin 18 cleavage in the cotyledon of IUGR animals. Placentome sections were stained for M30 using DAB substrate. Control and IUGR placentomes were stained with this antibody. A higher DAB staining was observed in the placentomes of IUGR animals as compared to controls.
Figure 5
Figure 5
HT and control cotyledon XIAP protein at mid gestation and near-term. A 1.7-fold and 2.4-fold decrease was observed for XIAP protein in the cotyledon of HT IUGR animals during mid-gestation and near-term, respectively.
Figure 6
Figure 6
HT and control caruncle XIAP protein at mid gestation and near-term. XIAP protein did not change during mid-gestation or near-term in the caruncle of treated animals vs. controls.
Figure 7
Figure 7
XIAP protein localization in the sheep placentome. Placentome sections stained with DAB demonstrated localization of XIAP protein to the villi of control and HT treated sheep placentomes (A and B). Serial placentome sections stained with NovaRED (trophoblast cells) and DAB (XIAP protein) demonstrated co-localization of XIAP protein to the trophoblast cells to the villi of the sheep placentome (C and D).
Figure 8
Figure 8
Correlation between XIAP and oxygen concentration between treatment groups. XIAP concentrations were increased in controls animals at both mid and near-term gestational points compared to HT groups. During HT treatment, XIAP concentration is inversely correlated with oxygen saturation at both time points.
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