Placental TRPV2 supports trophoblast function and normal fetal development
While placental functioning arbitrates fetal outcome, the molecular players that underpin normal placental development remain poorly understood. Here, we provide evidence that the Transient Receptor Potential Vanilloid 2 (TRPV2) channel plays an important role in normal placental development, determining fetal size and survival. Its absence severely affects placental morphology, causing fetal growth restriction and embryonic lethality, which was found to be allocated to a non-redundant role in the trophoblast, but not in the embryo. CRISPR/Cas9-mediated Trpv2 deletion in mouse trophoblast stem cells demonstrated that Trpv2 contributes to the differentiation towards Syncytiotrophoblast layer II (SynTII) cells, which was confirmed by the growth restriction phenotype in SynTII-specific Trpv2 knockout animals. Finally, TRPV2 was functionally expressed in human trophoblast cells and enriched in trophoblast populations undergoing syncytial differentiation. Together, our findings identify an important role for TRPV2 during placental development and consequently fetal outcomes. Normal placental development is fundamental to fetal outcome, yet the molecular pathways that underpin this process remain poorly defined. Here, the authors identify TRPV2 as an essential regulator of placental development. Loss of TRPV2 disrupts trophoblast differentiation and placental architecture, leading to fetal growth restriction, impaired survival and abnormal fetal development in mice.
Authors
- Joris Vriens (ORCID: https://orcid.org/0000-0002-2502-0409)
- Amitesh Panda (ORCID: https://orcid.org/0000-0002-2702-3494)
- Rudi Vennekens (ORCID: https://orcid.org/0000-0002-2564-5150)
- Thomas Voets (ORCID: https://orcid.org/0000-0001-5526-5821)
- Katrien Luyten
- Marta Wojno (ORCID: https://orcid.org/0000-0003-2711-1264)
- Jorge López‐Tello (ORCID: https://orcid.org/0000-0002-7886-0233)
- Amanda N. Sferruzzi‐Perri (ORCID: https://orcid.org/0000-0002-4931-4233)
- Anna L. David (ORCID: https://orcid.org/0000-0002-0199-6140)
- Katrien De Clercq (ORCID: https://orcid.org/0000-0002-7439-7587)
- Yuki Katanosaka (ORCID: https://orcid.org/0000-0002-0250-4312)
- Evy Van Den Broeck (ORCID: https://orcid.org/0000-0002-1691-9930)
- Suresh Poovathingal (ORCID: https://orcid.org/0000-0002-3236-2255)
- Vincent Pasque (ORCID: https://orcid.org/0000-0002-5129-0146)
- Andrei Segal (ORCID: https://orcid.org/0000-0002-0981-9587)
- Pilar Van Mechelen
- Seppe Gevaert
- Jill Witvrouwen
- Katarzyna Maksym
- Vicente Pérez-García
Institutions
- University College Hospital (GB)
- Kinjo Gakuin University (JP)
- Okayama University (JP)
- University of Cambridge (GB)
- Endometriosis UK (GB)
- VIB-KU Leuven Center for Microbiology (BE)
- National Research Council (LK)
- Max Planck Institute for Molecular Genetics (DE)
- Centro de Biología Molecular Severo Ochoa (ES)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- The Loke Centre for Trophoblast Research (GB)
- Leuven Stem Cell Institute (BE)
- University College London (GB)
- Universidad Autónoma de Madrid (ES)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-09-10
- DOI
- https://doi.org/10.1038/s41467-026-77576-z
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00