191 MATERNAL AGE ALTERS FETAL AND PLACENTAL DEVELOPMENT AND EXPRESSION OF METHYLATED GENES

Abstract

The objective of this experiment was to assess fetal and placental development and to determine the abundance of imprinted gene transcripts in fetal, placental, ovarian, and brain tissue, from aged (15 months old) and young (26 days old) B6D2F1 mice. Fetal and placental weight was measured, and transcript abundance of 14 imprinted genes and 3 nutrient transport genes was analyzed by quantitative PCR. The percentage of females pregnant at day 15.5 of gestation and the average number of normal implantation sites were significantly lower in aged mice, while the average number of degenerating implantation sites was significantly increased (P < 0.05). Fetal growth restriction and placental overgrowth were associated with maternal age, suggesting the balance between maternally and paternally expressed genes may be impaired. Peg3 and Grb10 tended to have decreased abundance in placental tissue collected from pregnancies in aged mice compared to young mice (P < 0.10). Abundance of Igf2, Igf2r, Cdkn1c, Slc2a3, Slc38a4, Peg3, and Phlda2 was significantly increased (P < 0.05) in ovarian tissue from aged mice. Brain tissue harvested from aged females displayed increased abundance of Igf2r, Snrpn, Slc2a3, Mest, Gtl2, Peg3, Grb10, and Lpl (P < 0.05). Aberrant transcript abundance of imprinted genes in ovarian and brain tissue harvested from aged mice suggests that hypothalamic regulation of oocyte growth, as well as oocyte imprinting, may be altered in older females. Abnormal fetal and placental development and differential expression of imprinted genes in the ovary and brain of aged mice suggests that epigenetic regulation of oocyte and fetal development is impaired with advanced maternal age.