Gq/11-Dependent Changes in the Murine Ovarian Transcriptome at the End of Gestation1

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Abstract

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 ofAkr1c18, 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 ofGalphaq/11with 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 ofGalphaq/11are still pregnant but their control littermates are 1-2 days postpartum. Ovarian genes up-regulated at the end of gestation in aGalphaq/11-dependent fashion include genes involved in focal adhesion and extracellular matrix interactions. Genes down-regulated at the end of gestation in aGalphaq/11-dependent manner includeSerpina6(which encodes corticosteroid-binding globulin);Enpp2(which encodes autotaxin, the enzyme responsible for the synthesis of lysophosphatidic acid); genes involved in protein processing and export; reproductive genes, such asLhcgr; the three genes needed to convert progesterone to estradiol (Cyp17a1,Hsd17b7, andCyp19a1); andInha. Activation of ovarian Gq/11 by engagement of 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.

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