Development and validation of trophoblast organoid model system for understanding the complexity of early placental development
Implementing Organization
Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raibarelly Road, Lucknow
Principal Investigator
Dr. Suman Mishra
Sanjay Gandhi Postgraduate Institute Of Medical Sciences
sumanm721@gmail.com
Project Overview
Pregnancy is a systemic process of development of the fetus; determined by cell growth, and a differentiation process that involves maternal adaptations to the increasing energy demands imposed by the growing fetus (Chappel, 2013). Failure to adjust to these energy requirements may result in serious health complications, both normal and pregnancy-related complications (Joo et al., 2021). During pregnancy, the placenta is known to have high mitochondria, hence, it has a major role in the regulation of mitochondrial metabolism and provides a protective environment for fetal development (Sanchez‑Aranguren and Nadeem, 2021). Energy disbalance or mitochondrial dysfunction is associated with many pregnancy-related complications, such as preeclampsia (PE), Intra Uterine (fetal) growth restriction (IUGR), gestational diabetes mellitus (GDM), and preterm birth (PTB), by damaging placentation (Joo et al., 2021). Pregnancy related complication have long-term effects on the progeny, but at present limited tools has been used for its diagnosis and characterization, thus limiting the efficacy of both clinical and public health interventions (Gurugubelli and Vishnu Bhat, 2018). Due to unavailability/limited availability of early placental samples, little is known about the molecular mechanism of these organelles at the early stages of gestation. Still, functional studies in early placental tissues are also limited and results available either from isolated term trophoblasts cells or animal models, and this approach is not representative of the developmental structures and characteristics of early trophoblasts. These limitations have hindered our understanding of the role and regulation of placenta at early stages and therefore have delayed the exploration of appropriate targets for effective treatments. Alternatives to the study of the placental role in pregnancy-related complications are exosomes and organoid culture. In circulation, tissue-derived nanovesicles (aka Exosomes) have gained substantial research attention as a liquid biopsy approach (Arshiya et al., 2021). In the last decade, organoids culture appeared as novel models for biomedical research (Turco et al., 2018). They are small self-organized 3D tissue cultures derived from stem cells that imitate tissue type, such as blastoid, endometrium, and trophoblast tissues (Seok et al., 2020). They provide useful models for studying the process, such as embryo implantation, female reproductive tract, and disease modelling. At present, the main ECM used in the endometrium organoid culture is matrigel to facilitate organoids in fully mimicking their counterparts in vivo tissues.
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