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Trophoblast fusion and function is regulated by biophysical features of the placental microenvironment during development and disease

Ma, Zhenwei Parameshwar, Parameshwar, Prabu Karthick, Sagrillo-Fagundes, Lucas, Tran, Raymond, Vaillancourt, Cathy ORCID: https://orcid.org/0000-0003-0543-6244 et Moraes, Christopher (2018). Trophoblast fusion and function is regulated by biophysical features of the placental microenvironment during development and disease In: Meeting of the International-Federation-of-Placenta-Associations (IFPA): Clinical Growth via Placenta, 21-24 September 2018, Tokyo, Japon.

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Résumé

Objectives: Biophysical features of the cellular microenvironment have emerged as critical regulators of development and disease in a variety of organs. However, the role of biomechanical forces in trophoblast biology remains undefined, despite evidence that placental tissue is mechanically and compositionally altered during tissue maturation. Our objectives in this work were to (1) apply engineering strategies to reconstruct biomechanically defined cultures that mimic placental tissue development, and (2) determine whether environmental mechanics plays a role in driving trophoblast fusion and function under normal and disease conditions.

Methods: Using microfabrication techniques developed by the electronics semiconductor industry, we constructed precisely-defined microscale culture environments in mechanically-tunable hydrogel materials to simulate mechanical rigidity, confinement and intracellular tension during villous tree morphogenesis. Tissue composition was modulated to mimic healthy and diseased conditions by decellularization and reconstruction of patient tissue samples. Finite element models were developed to quantitatively assess endogenous mechanical tension in these models arising from tissue shape and architecture. BeWo cells and human villous cytotrophoblasts isolated during healthy vaginal delivery at term were used as model systems; for which syncytial fusion and hormone production were evaluated.

Results: Optimal trophoblast fusion and hCG production was observed on surfaces that mimic the rigidity of healthy placental tissue (~1 kPa), while surfaces that recreate preeclampsia and intrauterine growth restriction tissue mechanics (~ 7 kPa) significantly inhibited long-range fusion and increased hCG expression. Recreating endogenous mechanical tension patterns present during the dynamic process of villous tree formation resulted in greatly elevated fusion levels via a myosin-dependent pathway, confirming that mechanical forces play a critical role in syncytial formation and disruption.

Conclusion: The mechanosensitivity of trophoblasts to developmental biomechanical signals indicates that the in vivo fusion process is highly efficient because it occurs in a dynamic environment, suggesting novel approaches with which to engineer better models for placental disease.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Conférence MC8 Placenta 83:E13
Mots-clés libres: *
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 15 juill. 2021 14:40
Dernière modification: 16 févr. 2022 15:25
URI: https://espace.inrs.ca/id/eprint/11730

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