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Elevated Apoptosis in Ovine Intrauterine Growth Restriction (IUGR) is Associated with Increased Caspase 3 and 9 and Decreased Telomerase Activity
Author(s) -
Mika Aleksander,
Reynolds Paul,
Arroyo Juan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.978.2
Subject(s) - telomerase , apoptosis , intrauterine growth restriction , gestation , andrology , caspase 3 , biology , placenta , fetus , medicine , endocrinology , programmed cell death , pregnancy , gene , biochemistry , genetics
Intrauterine growth restriction (IUGR) has been documented to increase placental apoptosis at term. Previous reports from our lab showed apoptosis as an early event in an ovine model of IUGR. Our objective was to determine the placental expression of apoptotic proteins and telomerase activity at early (55 days of gestation; DGA), mid (95 dGA) and near term gestation (130 dGA) in a hyperthermia (HT) induced model of IUGR. Pregnant sheep were placed in hyperthermic (HT) conditions and placental tissues were collected at 55, 95 and 130 dGA. Compared to controls we found: 1) increased telomerase activity at day 55 dGA (1.3‐fold; p <0.007) with decreased activity at 130 dGA (1.3‐fold;p <0.02); 2) increased cleaved caspase 9 only at 95 dGA (1.6‐fold; p <0.008); 3) no significant differences for BAX protein across gestation; 4) increased caspase 3 at 95 and 130 dGA; and 5) decreased Bcl2 protein at 55 dGA (1.6‐fold; p < 0.02) with decreased expression at 95 dGA (1.4‐fold; p< 0.02). We conclude that elevated placental apoptosis near term coincides with decreased telomerase activity, increased caspase 3, and inhibition of active Bcl2. These data suggest that several mitochondrial pro‐apoptotic genes contribute to the induction of placental apoptosis during IUGR.