Calcium-selective transient receptor potential Vanilloid 6 (TRPV6) channels are expressed in
fetal labyrinth trophoblasts as part of the feto–maternal barrier, necessary for sufficient calcium supply,
embryo growth, and bone development during pregnancy. Recently, we have shown a less- compact
labyrinth morphology of Trpv6-deficient placentae, and reduced Ca2+ uptake of primary trophoblasts
upon functional deletion of TRPV6. Trpv6-/-
trophoblasts show a distinct calcium-dependent phenotype.
Deep proteomic profiling of wt and Trpv6-/- primary trophoblasts using label-free quantitative mass
spectrometry leads to the identification of 2778 proteins. Among those, a group of proteases,
including high-temperature requirement A serine peptidase 1 (HTRA1) and different granzymes
are more abundantly expressed in Trpv6-/-
trophoblast lysates, whereas the extracellular matrix
protein fibronectin and the fibronectin-domain-containing protein 3A (FND3A) were markedly
reduced. Trpv6-/- placenta lysates contain a higher intrinsic proteolytic activity increasing fibronectin
degradation. Our results show that the extracellular matrix formation of the placental labyrinth
depends on TRPV6; its deletion in trophoblasts correlates with the increased expression of proteases
controlling the extracellular matrix in the labyrinth during pregnancy