Expression and functional implications of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in canine reproductive tissues during normal pregnancy and parturition and at antiprogestin induced abortion

PPAR gamma is a nuclear hormone receptor of the PPAR family of transcription factors closely related to the steroid hormone receptors serving multiple roles in regulating reproductive function. Endogenous factors from the arachidonic acid metabolites group serve as ligands for PPARs. PPAR gamma modifies the steroidogenic capacity of reproductive tissues and has been defined as a key mediator of biological actions of progesterone receptor in granulosa cells; it modulates biochemical and morphological placental trophoblast differentiation during implantation and placentation. However, no such information is available for the dog. Hence, the expression and possible functions of PPAR gamma were assessed in corpora lutea (CL) and utero/placental (Ut/Pl) compartment collected from bitches (n = 3 to 5) on days 8 to 12 (pre-implantation), 18 to 25 (post-implantation), 35 to 40 (mid-gestation) of pregnancy and at prepartal luteolysis. Additionally, 10 mid-pregnant bitches were treated with the antiprogestin Aglepristone [10mg/Kg bw (2x124h)]; ovariohysterectomy was 24h and 72h after the 2nd treatment. Of the two PPAR gamma isoforms, PPAR gamma 1 was the only isoform clearly detectable in all canine CL and utero/placental samples. The luteal PPAR gamma was upregulated throughout pregnancy, a prepartal downregulation was observed. Placental expression of PPAR gamma was elevated after implantation and at mid-gestation, followed by a prepartal downregulation. All changes were more pronounced at the protein-level suggesting that the PPAR gamma expression may be regulated at the post-transcriptional level. Within the CL PPAR gamma was localized to the luteal cells. Placental expression was targeted solely to the fetal trophoblast cells; a regulatory role of PPAR gamma in canine placental development possibly through influencing the invasion of fetal trophoblast cells is suggested. Treatment with Aglepristone led to downregulation of PPAR gamma in either compartment, implying the functional interrelationship with progesterone receptor. (C) 2011 Elsevier Inc. All rights reserved.