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

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 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 postpartum. Ovarian genes up-regulated at the end of gestation in a 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); Enpp2 (which encodes autotaxin, the enzyme responsible for the synthesis of lysophosphatidic acid); genes involved in protein processing and export; reproductive genes, such as Lhcgr; the three genes needed to convert progesterone to estradiol (Cyp17a1, Hsd17b7, and Cyp19a1); and Inha. 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.

Proteomics Analysis of Serum Proteins in Gestational Diabetes

“…It has been reported that increased ENPP2 expression in adipose tissue is closely related to impaired glucose homeostasis and/or insulin resistance [ 22 ], while ENPP2 gene regulation affects immune cell population and tissue inflammation in adipose tissue [ 23 ]. Although studies have shown that ENPP2 may play a role in induction of parturition [ 24 , 25 ], the relationship between ENPP2 and the onset of GDM remains to be determined. Given that increased expression of ENPP2 protein may be related to GDM, it needs to be further investigated whether ENPP2 is involved in GDM pathogenesis and can act as a potential biomarker.…”

Proteomics Analysis of Serum Proteins in Gestational Diabetes

“…It has been reported that increased ENPP2 expression in adipose tissue is closely related to impaired glucose homeostasis and/or insulin resistance [22], while ENPP2 gene regulation affects immune cell population and tissue in ammation in adipose tissue [23]. Although studies have shown that ENPP2 may play a role in induction of parturition [24,25], the relationship between ENPP2 and the onset of GDM remains to be determined. Given that increased expression of ENPP2 protein may be related to GDM, it needs to be further investigated whether ENPP2 is involved in GDM pathogenesis and can act as a potential biomarker.…”

Prostaglandin F2α promotes embryo implantation and development in the pig

“…Interestingly, PGF2α has been reported to stimulate tyrosine phosphorylation of p125 FAK in NIH-3T3 cells (Watanabe et al 1994) and in 293-EBNA cells stably expressing isoform A of the PTGFR prostanoid receptor (Pierce et al 1999). PTGFR is a G-protein-coupled receptor activating Gq11 protein (Bos et al 2004), and it has been demonstrated that genes upregulated at the end of gestation in a Gαq/11-dependent manner in ovarian (granulosa/ luteal) cells included genes involved in focal adhesion and ECM interactions (Waite et al 2016). Moreover, in human adenocarcinoma cells (Ishikawa cell line), PGF2α was able to induce MAPK1/3 phosphorylation (Sales et al 2005).…”