The Maternal Fetal Interface (MFI) is a unique compartment where two tissues with different genetic origins interact. In humans, the MFI is very intimate, with fetal trophoblasts invading deeply into the maternal endometrium.
In our lab, we identify the intercellular communication between fetal and maternal tissues, and their causality in regulating placentation.
Overall, our thesis suggest that there is both competition, and coopetition at MFI — Co-opetition, driven by cooperation of the maternal tissues in regulating their own invasion. Deviations from these tightly controlled regulation result in pathologies, one of which we are very interested in: Placenta Accreta Spectrum (PAS).
Key Findings
- Decidualization of endometrium is a “wound healing” like response resulting in increase in resistance to trophoblast invasion. However, in apes, the recently evolved extravillous trophoblasts (EVTs) can partially reverse this maternal resistance. This is achieved by various secreted factors, including HBEGF, IL11, TGF beta inhibitors and other molecules from the EVTs. (Afzal J. et al., Front. Cell. Dev. Bio., 2022).
- Placenta Accreta Spectrum (PAS) is an outcome of decidual inflammation proximal to the site of cesarean scar. The scar changes the mechanical microenvironment, which transforms the decidual fibroblasts to recruit EVTs towards themselves. This happens by activation of Piezo1 channels, which by increased intracellular Ca2+ causes high Protein Kinase C activation, and subsequently NFkB activation. We also showed that IL8, and G-CSF secreted at the site of scar by the transformed decidua can act as a “recruiting center” for EVTs, initiating PAS. (Du).
Relevant Publications
- Du W, Novin A, Liu Y, Afzal J, Suhail Y, Gavin NR, Jorgensen J, Schmidt T, Morosky CM, Sanders M, Brewer M, Kshitiz (2024), Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum, Nature Communications, 8379.
- Afzal J*, Du W*, Novin A, Liu Y, Wagner G, Kshitiz (2022), Paracrine HB-EGF signaling reduce enhanced contractile and energetic state of activated decidual fibroblasts by rebalancing SRF-MRTF-TCF transcriptional axis, Frontiers in Cell & Development Biology, 10, 927631.
- Novin A, Suhail Y, Ajeti V, Goyal R, Wali K, Seck A, Jackson A, Kshitiz (2021). Diversity in cancer invasion phenotypes indicates specific stroma regulated programs, Human Cell, 34(1), 111-121.
- Kshitiz*±, Ellison DE*, Suhail Y*, Afzal J, Woo L, Kilic O, Spees J, Levchenko A± (2019). Dynamic Secretome of Bone Marrow Derived Stromal Cells Reveals a Cardio-protective Biochemical Cocktail, Proceedings of the National Academy of Sciences, 116(28), 14374-83. ±: Corresponding Authors