Page 14 - HKSEMR2020 Programme book

Oral Presentation (Basic Science) Abstracts

Biological role of the human endometrial organoid secretome on

extravillous trophoblast migration and invasion

Yang Dong, Cheuk-Lun Lee, Calvin K.F. Lee, Philip C.N. Chiu
Department of Obstetrics and Gynecology, The University of Hong Kong, Pokfulam Road, Hong Kong SAR;
Shenzhen Key Laboratory of Fertility Regulation, Department of Obstetrics and Gynecology, The University of Hong
Kong-Shenzhen Hospital.

Introduction / Background / Objectives: Results / Outcomes:
The migration and invasion of extravillous trophoblasts into the Endometrial organoids with high expressions of endometrial
endometrium during early pregnancy is crucial to placentation. gland markers, FOXA2, E-cadherin, PAEP, PAX8 and SOX17 were
Dysregulation of trophoblast migration and invasion is associated successfully formed and were treated with hormones mimicking
with various pregnancy complications, e.g. miscarriage, the environment of the proliferative phase (E2), the secretory phase
preeclampsia and intrauterine growth restriction (IUGR). Successful (E2+P4) and early pregnancy (E2+P4, hCG) for 1 week. The mRNA,
placentation requires communication between the endometrium miRNA and proteome expression profiles of endometrium organoids
and trophoblasts. The endometrial microenvironment, constituted during different physiological phases were analyzed after collecting
by luminal and glandular epithelial cells and stromal cells, the secretions. Differentially expressed gene (DEG), miRNAs (DEMs)
undergoes cyclical changes regulated by sex hormones. Evidence and secretory proteins (DEPs) were then verified. Networks of
indicates that the uterine microenvironment exerts important miRNA-RNA-protein for organoids and their products were also
influence over trophoblast cell functions. However, the precise analyzed. Spent medium from E2+P4+hCG-treated endometrial
effect and mechanism of the endometrium gland secretome on organoids, which mimics the early pregnant microenvironment,
trophoblast cell functions long remained unidentified due to a lack significantly enhanced the migration and invasion of the
of suitable research models. This research gap was finally filled by trophoblasts compared to those obtained from proliferative/
the establishment of an ex vivo three-dimensional (3D) endometrial secretory phases. Conversely, the S100A9 blocking antibody
glandular epithelial organoid system that allowed for long-term significantly impeded the enhancement effect of the conditioned
expansion. In this study, we adopted the endometrial organoid as medium from the early pregnancy phase on trophoblast migration
a model to simulate the endometrium in the menstrual cycle and and invasion. Meanwhile, none of the treatments, including the
early gestation using hormone stimulations. blocking antibody, had any effect on trophoblast viability.

Methods: Conclusion:
Human endometrial tissues were obtained from endometrial Using a human endometrial organoid model, we demonstrated that
biopsies with written consent. The endometrial organoids were hormonal regulation of the decidual secretome during pregnancy
established in matrix gel using a defined culture condition. The might be crucial for controlling the migration capability and
organoids were treated with hormones mimicking the environment invasiveness of human trophoblasts.
of the proliferative phase (estrogen, E2), the secretory phase
(E2+ progesterone, P4) and pregnancy (E2+P4+human chorionic
gonadotropin, hCG) for 1 week. The spent medium of the organoids
was collected for omics studies (mRNA, microRNA [miRNA] and
proteome) and used to treat the trophoblasts. After treatment, the
cell viability and invasion/migration of the trophoblasts were then
determined by CCK8 and Transwell assays, respectively.

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