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.During early pregnancy in the pig, porcine conceptuses (embryos with associated membranes) secrete E2, which is regarded as the pregnancy recognition signal required for prolonged progesterone synthesis and secretion by corpora lutea (CLs). Porcine conceptuses secrete estrogens in a biphasic manner-the first increase of conceptus-derived estrogens occurs on days 11-13 after fertilization and the second is between days 15 and 25-30 after fertilization (reviewed in [2]). However, the levels of conceptus-derived estrogens in the uterine lumen may also vary depending on the number of conceptuses [1]. The period of elevated E2 synthesis and secretion by porcine conceptuses between days 11-13 of pregnancy is a process defined as the maternal recognition of pregnancy [5]. This is the critical period for establishment and development of pregnancy as the highest mortality rate of embryos in animals including pigs is observed during the peri-implantation period [6]. Embryonic estrogen synthesis and secretion not only prolongs the CL lifespan but also enhances P4-induced endometrial receptivity for implantation. Following the decrease of the progesterone receptor expression in the endometrial luminal and glandular epithelia, the expression of the estrogen receptor (ESR1) is up-regulated in these structures, which in turn is important for the cell-specific responses to conceptus estrogens released on day 12 of pregnancy [7]. Estrogen is involved in stimulation of uterine secretory activity [8], increased blood flow [9], endometrial edema [10], and the regul...

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.

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