Synergistic action of estradiol and PGE2 on endometrial transcriptome in vivo resembles pregnancy effects better than estradiol alone

Successful pregnancy establishment in mammals depends on numerous interactions between embryos and the maternal organism. Estradiol-17β (E2) is the primary embryonic signal in the pig, and its importance has been questioned recently. However, E2 is not the only molecule of embryonic origin. In pigs, prostaglandin E2 (PGE2) is abundantly synthesized and secreted by conceptuses and endometrium. The present study aimed to determine the role of PGE2 and its simultaneous action with E2 in changes in porcine endometrial transcriptome during pregnancy establishment. The effects of PGE2 and PGE2 acting with E2 were studied using an in vivo model of intrauterine hormone infusions, and were compared to the effects of E2 alone and conceptuses' presence on day 12 of pregnancy. The endometrial transcriptome was profiled using gene expression microarrays followed by statistical analyses. Downstream analyses were performed using bioinformatics tools. Differential expression of selected genes was verified by quantitative PCR. Microarray analysis revealed 2413 differentially expressed genes (DEGs) in the endometrium treated simultaneously with PGE2 and E2 (P < 0.01). No significant effect of PGE2 administered alone on endometrial transcriptome was detected. Gene ontology annotations enriched for DEGs were related to multiple processes such as: focal adhesion, vascularization, cell migration and proliferation, glucose metabolism, tissue remodeling, and activation of immune response. Simultaneous administration of E2 and PGE2 induced more changes within endometrial transcriptome characteristic to pregnancy than infusion of E2 alone. The present findings suggest that synergistic action of estradiol-17β and PGE2 resembles the effects of pregnancy on endometrial transcriptome better than E2 alone

Prostaglandin F2α promotes embryo implantation and development in the pig

Successful establishment and development of pregnancy requires proper communication between developing conceptuses and the maternal reproductive tract. Prostaglandins are key players involved in the regulation of reproductive processes in mammals including pigs. Due to its luteolytic action, prostaglandin F2-alpha (PGF2α) is mainly considered as an undesirable factor during early pregnancy. However, its content in the uterine lumen is elevated in pigs and other mammals. Recently, we reported an important role of PGF2α in the endometrium during early pregnancy in the pig. Thus, the aim of the present study was to determine whether PGF2α can act on porcine trophoblast and if so, to elucidate what effect it could exert. We detected increased expression of PGF2α receptor during the implantation period (from day 14 until day 19 of pregnancy). Global gene expression profiling using microarrays and quantitative PCR studies revealed that PGF2α acting on porcine trophoblast cells in vitro alters expression of genes potentially involved in processes related to implantation, such as: cell proliferation, focal adhesion, extracellular matrix binding, cell migration, cytoskeleton organization, immune interactions, ion homeostasis, and lipid metabolism. Using primary porcine trophoblast cells, we demonstrated that PGF2α stimulated trophoblast cell proliferation and adhesion to extracellular matrix protein. This was likely mediated by mitogen-activated protein kinases (MAPK1/3) and focal adhesion kinase (FAK) since we observed increased phosphorylation of MAPK1/3 and FAK in trophoblast cells treated with PGF2α. To conclude, the present report indicates a novel role for PGF2α in the porcine conceptus as a para- and autocrine factor supporting pregnancy establishment

Estradiol-17β Regulates Expression of Luteal DNA Methyltransferases and Genes Involved in the Porcine Corpus Luteum Function In Vivo

The corpus luteum (CL) is a temporary endocrine gland vital for pregnancy establishment and maintenance. Estradiol-17β (E2) is the major embryonic signal in pigs supporting the CL’s function. The mechanisms of the luteoprotective action of E2 are still unclear. The present study aimed to determine the effect of E2 on luteal expression of factors involved in CL function. An in vivo model of intrauterine E2 infusions was applied. Gilts on day 12 of pregnancy and the estrous cycle were used as referential groups. Concentrations of E2 and progesterone were elevated in CLs of gilts receiving E2 infusions, compared to placebo-treated gilts. Estradiol-17β stimulated luteal expression of DNA-methyltransferase 1 (DNMT1), but decreased expression of DNMT3B gene and protein, as well as DNMT3A protein. Similar results for DNMT3A and 3B were observed in CLs on day 12 of pregnancy compared to day 12 of the estrous cycle. Intrauterine infusions of E2 altered luteal expression of the genes involved in CL function: PTGFR, PTGES, STAR, HSD17B1, CYP19A1, and PGRMC1. Our findings indicate a role for E2 in expression regulation of factors related to CL function and a novel potential for E2 to regulate DNA methylation as putative physiological mechanisms controlling luteal gene expression

Estradiol-17β-induced changes in the porcine endometrial transcriptome in vivo

Estradiol-17β (E2) is a key hormone regulating reproductive functions in females. In pigs, E2, as the main conceptus signal, initiates processes resulting in prolonged corpus luteum function, embryo development, and implantation. During early pregnancy the endometrium undergoes morphological and physiological transitions that are tightly related to transcriptome changes. Recently, however, the importance of E2 as a primary conceptus signal in the pig has been questionable. Thus, the aim of the present study was to determine the effects of E2 on the porcine endometrial transcriptome in vivo and to compare these effects with transcriptome profiles on day 12 of pregnancy. Microarray analysis revealed differentially expressed genes (DEGs) in response to E2 with overrepresented functional terms related to secretive functions, extracellular vesicles, cell adhesion, proliferation and differentiation, tissue rearrangements, immune response, lipid metabolism, and many others. Numerous common DEGs and processes for the endometrium on day 12 of pregnancy and E2-treated endometrium were identified. In summary, the present study is the first evidence for the effect of E2 on transcriptome profiles in porcine endometrium in vivo in the period corresponding to the maternal recognition of pregnancy. The presented results provide a valuable resource for further targeted studies considering genes and pathways regulated by conceptus-derived estrogens and their role in pregnancy establishment

Prokineticin 1 is a novel factor regulating porcine corpus luteum function

Abstract Prokineticin 1 (PROK1) is a pleiotropic factor secreted by endocrine glands; however, its role has not been studied in the corpus luteum (CL) during pregnancy in any species. The present study aimed to investigate the contribution of PROK1 in regulating processes related to porcine CL function and regression: steroidogenesis, luteal cell apoptosis and viability, and angiogenesis. The luteal expression of PROK1 was greater on Days 12 and 14 of pregnancy compared to Day 9. PROK1 protein expression during pregnancy increased gradually and peaked on Day 14, when it was also significantly higher than that on Day 14 of the estrous cycle. Prokineticin receptor 1 (PROKR1) mRNA abundance increased on Days 12 and 14 of pregnancy, whereas PROKR2 elevated on Day 14 of the estrous cycle. PROK1, acting via PROKR1, stimulated the expression of genes involved in progesterone synthesis, as well as progesterone secretion by luteal tissue. PROK1–PROKR1 signaling reduced apoptosis and increased the viability of luteal cells. PROK1 acting through PROKR1 stimulated angiogenesis by increasing capillary-like structure formation by luteal endothelial cells and elevating angiogenin gene expression and VEGFA secretion by luteal tissue. Our results indicate that PROK1 regulates processes vital for maintaining luteal function during early pregnancy and the mid-luteal phase

Link between Financial Management Behaviours and Quality of Relationship and Overall Life Satisfaction among Married and Cohabiting Couples: Insights from Application of Artificial Neural Networks

Background: To explain the link between household finances and the quality of the relationship between married or cohabitating partners and their life satisfaction, the Family Stress Model (FSM) was used and placed within the theoretical framework of the Couples and Finances Theory (CFT). Methods: The measures used to examine the relationship between partners were the Financial Management Behaviour Scale, the Marriage Questionnaire (KDM-2) adapted to a version for cohabitating couples, The Shared Goals and Values Scale, Harsh Start-up Scale, and the Satisfaction With Life Scale (SWLS). In order to find out the relationship between variables, artificial neural networks (ANN) were applied. The research was conducted on a sample of 500 couples living in Poland (384 married and 116 cohabitating couples). Results: The results indicate that overall life satisfaction is most influenced by fundamental, direct, current ways of dealing with the daily financial routine and by saving and investing behaviours. Credit management and insurance behaviours are the most important for the quality of the relationship between partners. Conclusions: The research shows that financial management behaviours have an impact on the quality of relationships as well as on the subjective well-being of people in a relationship, and their relationship dynamics. This finding may be used to highlight the psychological importance of financial management behaviours.This article belongs to the Special Issue The Economics of Health BehaviorsThis research was funded by the Ministry of Science and Higher Education, Republic of Poland, grant number 0057/DLG/2016/10. The APC was funded by the University of Economics and Innovation, Lublin, Poland

Novel role for conceptus signals in mRNA expression regulation by DNA methylation in porcine endometrium during early pregnancy

During early pregnancy, porcine conceptuses (the embryos with associated membranes) secrete estradiol-17β (E2)—their major signal for maternal recognition of pregnancy—and prostaglandin E2 (PGE2). Both hormones induce prominent changes of the endometrial transcriptome in vivo. Studies on endometrial pathologies have shown that E2 affects gene expression by epigenetic mechanisms related to DNA methylation. Herein, we determined the effects of E2 and PGE2 alone, and a combined E2 + PGE2 treatment administered into the uterine lumen in vivo on the expression and activity of DNA-methyltransferases (DNMTs) and on CpG methylation patterns of selected genes in porcine endometrium. To compare the effect of treatment with the physiological effect of pregnancy, endometria from day 12 pregnant/cyclic gilts were included. Both E2 and PGE2 significantly reduced the expression of DNMTs. Likewise, the expressions of DNMT1 and DNMT3A were decreased on day 12 of pregnancy compared to the estrous cycle. DNMT activity increased in endometrial samples following E2 treatment and in gilts on day 12 of pregnancy. Treatment with E2 alone and/or simultaneously with PGE2 altered endometrial DNA methylation of CpG sites of ADAMTS20, ADH1C, BGN, PSAT1, and WNT5A. Different CpG methylation patterns of ADAMTS20, BGN, DMBT1, RASSF1, and WNT5A were found in the endometrium on day 12 of pregnancy compared to day 12 of the estrous cycle. Significant correlations were detected between CpG methylation and gene expression for ADAMTS20, ADH1C, BGN, DMBT1, PSAT1, and WNT5A. Our results indicate that CpG methylation induced by embryonic signals may contribute to regulating endometrial gene expression during pregnancy establishment.ISSN:0006-3363ISSN:1529-726