Courtney Waite, Rachel Mejia, Mario Ascoli

Parturition in rodents is highly dependent on the engagement of the luteal prostaglandin F2 alpha receptor which, through activation of the Gq/11 family of G proteins increases the expression of Akr1c18 leading to an increase in progesterone catabolism. To further understand the involvement of Gq/11 on luteolysis and parturition we used microarray analysis to compare the ovarian transcriptome of mice with a granulosa/luteal cell-specific deletion of Galphaq/11 with their control littermates on Day 18 of pregnancy when mice from both genotypes are pregnant and on Day 22 when mice with a granulosa/luteal cell-specific deletion of Galphaq/11 are still pregnant but their control littermates are 1-2 days post-partum. Ovarian genes up-regulated at the end of gestation in Galphaq/11-dependent fashion include genes involved in focal adhesion and extracellular matrix interactions. Genes down-regulated at the end of gestation in a Galphaq/11-dependent manner include Serpina6 (which encodes corticosteroid binding globulin) and Enpp2 (which encodes autotaxin, the enzyme responsible for the synthesis of lysophosphatidic acid), genes involved in protein processing and export and reproductive genes such as the Lhcgr; the three genes needed to convert progesterone to estradiol (Cyp17a1, Hsd17b7 and Cyp19a1) and Inha. Activation of ovarian Gq/11 by engaging the prostaglandin F2 alpha receptor on Day 18 of pregnancy recapitulated the regulation of many, but not all of these genes. Thus, although the ovarian transcriptome at the end of gestation is highly dependent on the activation of Gq/11, not all of these changes are dependent on the actions of prostaglandin F2 alpha.