Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo.

Piotr Kaczynski,Stefan Bauersachs,Monika Baryla,Ewelina Goryszewska,Agnieszka Waclawik,Jolanta Muszak,Waldemar J Grzegorzewski

doi:10.3390/ijms21030890

Abstract

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.

Highlights

Local autocrine-paracrine signaling at the embryo-maternal interface is crucial for the successful establishment of pregnancy
The present study is the first demonstrating the effect of E2 on the global gene expression profile in porcine endometrium in vivo during the time corresponding to the maternal recognition of pregnancy
We found that a lower dose of E2 (833 ng/infusion) resulted in smaller alterations within the endometrial transcriptome, whereas a higher dose of E2 (33.3 μg/infusion) induced more changes in the global gene expression profile that were similar to changes identified in day 12 of the pregnancy endometrial transcriptome

Summary

Introduction

Local autocrine-paracrine signaling at the embryo-maternal interface is crucial for the successful establishment of pregnancy. Reduced fertility is a serious problem in animal and human reproduction. Pregnancy losses significantly decrease the profitability in animal production. The reasons for unsuccessful implantation are associated with the embryo e.g., insufficient conceptus signaling [1], genetic disorders, and impaired endometrial receptivity (reviewed in [2]). Estradiol-17β (E2) serves as a pivotal molecule regulating reproductive functions of the female reproductive tract. Estrogens secreted by ovarian follicles prior to ovulation are required for regeneration and growth of the endometrium and prime the tissue for progesterone (P4) (reviewed in [3]). Progesterone, called a “pregnancy hormone”, in turn regulates endometrial receptiveness, enabling conceptus implantation and early pregnancy development (reviewed in [4])

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