Nuclear progesterone receptor-regulated gene networks in the oviduct: Potential mediators of progesterone action on oviductal transport. — ASN Events
  1. Schedule
  2. SRB Poster Session - Gene regulation
  3. Nuclear progesterone receptor-regulated gene networks in the oviduct: Potential mediators of progesterone action on oviductal transport.

Nuclear progesterone receptor-regulated gene networks in the oviduct: Potential mediators of progesterone action on oviductal transport. (#209)

Lisa K Akison 1 , Michael J Boden 1 , David J Kennaway 1 , Darryl L Russell 1 , Rebecca L Robker 1
  1. Robinson Institute, School of Paediatrics & Reproductive Health, University of Adelaide, Adelaide, SA, Australia

The oviducts are critical for gamete/embryo transport and fertilisation. Nuclear progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, concomitant with high progesterone (P4) levels approaching ovulation. P4 affects oviduct cilia and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR-knockout (PRKO) mice to determine how PGR regulates gene expression in the oviduct during the periovulatory period. H&E-stained, paraffin-embedded sections of oviducts from PRKO and heterozygous (PR+/-) mice at eCG + 8h, 10h, 12h or 14h-hCG showed no structural or morphological differences between genotypes (n=4 animals/genotype/time point). However, microarray analysis of pooled oviducts from PRKO and PR+/- mice at eCG + 8h hCG (n=5 samples/genotype), when P4 levels are high, revealed 1003 PGR-regulated genes (P<0.05). Gene ontology analysis identified significant associations with the functions of cell adhesion, migration, invasion, chemotaxis, muscle contraction and vasoconstriction. Twelve genes were selected for validation using RT-PCR based on their potential roles in oocyte/embryo transport and support. Oviducts were collected at eCG + 0h, 4h, 8h or 10h-hCG (n=5/genotype/time point). Most targets were up-regulated by LH in normal, PR+/- oviducts, peaking at 8h post-hCG. Nine were confirmed to be regulated by PGR, particularly Edn3, Itga8, Prlr and Adamts1 (24-, 12-, 5- and 5-fold down-regulated in PRKO at 8h post-hCG). Expression of these genes was also assessed in oviducts of naturally cycling, mated mice at 4h intervals during ovulation, d1 and d4 of pregnancy (4-6 mice/time-point). Interestingly, Prlr and Ptgfr showed circadian cyclic induction on d1 and d4 of pregnancy. Adamts1, Itga8 and Edn3 were significantly up-regulated in oviducts at ovulation/mating, but were basally expressed at other times. This is the first, comprehensive study to examine PGR-regulated genes in the oviduct and reveals key downstream targets potentially mediating oocyte and embryo transport.

@ESASRB