Luteal estrogen receptor, interleukin-1, and apoptosis-associated genes during prostaglandin F2alpha-induced luteolysis in rabbits at different stages of pseudopregnancy

In rabbits, several intraluteal pathways have emerged as potential mediators of the luteolytic action of prostaglandin F2αPGF2α, but the mechanisms that protect the developing corpora lutea (CL) from functional luteolysis to occur up to day 5 of pseudopregnancy are still unclear. Thus, the aim of this study was to elucidate PGF2α-induced temporal expression changes for estrogen receptor (ERα), interleukin-1(IL-1β), p53, and Bcl-x genes in day 4 vs. day 9 CL, in order to further characterize their role in the acquisition of luteal capacity to PGF2α. CL were collected from rabbits 0, 1.5, 3, 6, 12, and 24 h after 200 μg i.m. PGF2α (alfaprostol) injection given at either day 4 or 9 of pseudopregnancy induced by 0.8 μg i.m. GnRH administration. mRNA was extracted at different time points and multiplex RT-PCR technique was used to obtain semi-quantitative abundances of target genes. Before treatment, ERαmRNA steady state levels were lower (P<0.01) in day 4 than in day 9 CL. At day 4, luteal ERαmRNA levels remained fairly constant after treatment, whereas at day 9 gradually declined to low values (P<0.01) within 6 h after PGF2αinjection. At day 4, IL-1β mRNA transcript peaked (P≤0.01) two-fold 3 h after PGF2α challenge and thereafter gradually fell to pre-treatment values, whereas at day 9 the peak level was reached 6 h after PGF2α. Before treatment, Bcl-x transcripts were higher (P<0.01) in day 4 than in day 9 CL. At day 4, the Bcl-x mRNA levels gradually dropped within the first 3 h after PGF2α and then remained unchanged thereafter. At day 9, Bcl-x mRNA relative abundance decreased (P<0.01) 6 h after PGF2α administration to reach the lowest values (P<0.01) 24 h later. Pretreatment p53 mRNA values did not differ between luteal stages. At day 4, p53 mRNA progressively declined within the following 24 h after treatment. At day 9, p53 mRNA increased up to 3 h after PGF2α and then diminished. In conclusion, these findings suggest that PGF2α regulates luteolysis by ERαmRNA downregulation and by modulation of pro- and anti-apoptotic pathways in CL that have acquired luteolytic capacity.