Maternal Transient Receptor Potential Vanilloid 6 (Trpv6) Is Involved In Offspring Bone Development

Abstract

Embryonic growth and bone development depend on placental Ca2+ transport across the feto‐maternal barrier to supply minerals to the fetus. The individual factors and cellular mechanisms that regulate placental Ca2+ transfer, however, are only beginning to emerge. We find that the Ca2+‐selective transient receptor potential vanilloid 6 (TRPV6) channel is expressed in trophoblasts of the fetal labyrinth, in the yolk sac, and in the maternal part of the placenta. Lack of functional TRPV6 channels in the mother leads to a reduced Ca2+ content in both placenta and embryo. Ca2+ uptake in trophoblasts is impaired in the absence of Trpv6. Trpv6‐deficient embryos are smaller, have a lower body weight, and shorter and less calcified femurs. The altered cortical bone microarchitecture persists in adulthood. We show that TRPV6's Ca2+‐conducting property causes this embryonic and bone phenotype. Our results show that TRPV6 is necessary for the Ca2+ uptake in trophoblasts and that TRPV6 deficiency in the placenta leads to reduced embryo growth, minor bone calcification, and impaired bone development. © 2019 American Society for Bone and Mineral Research.

Post-mortem histology in transient receptor potential cation channel subfamily V member 6 (TRPV6) under-mineralising skeletal dysplasia suggests postnatal skeletal recovery: a case report

“…Optimism arises from other recent cases suggesting normal postnatal growth, although duration is currently short with minimal linear growth details. Yet recent Trpv6 mouse model studies by Fecher-Trost give caution as cortical bone architecture remained abnormal in thickness with reduced femoral length [15].…”

Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor

“…4,5 It is known that TRPV6 has an important contribution to multifactorial diseases. 6,7 For instance, TRPV6-deficient mice have diminished fertility, osteopenia and reduced body weight, 5,8 whilst human TRPV6 mutations, which render the channel less functional, cause transient neonatal hyperparathyroidism (TNH) and skeletal abnormalities. 9,10 These pathological findings are related to tissues in which TRPV6-expression at normal levels is essential for Ca 2+ homeostasis.…”

“… 1 – 3 The channel is primarily found in the human intestine, kidney and placenta and in a number of exocrine organs such as pancreas, prostate and mammary gland. 4 , 5 It is known that TRPV6 has an important contribution to multifactorial diseases. 6 , 7 For instance, TRPV6-deficient mice have diminished fertility, osteopenia and reduced body weight, 5 , 8 whilst human TRPV6 mutations, which render the channel less functional, cause transient neonatal hyperparathyroidism (TNH) and skeletal abnormalities.…”

TRPV6 and Cav1.3 Mediate Distal Small Intestine Calcium Absorption Before Weaning

“…Interestingly, infants born with TRPV6 mutations have skeletal abnormalities detectable in utero 43, 44. This human phenotype is likely the result of decreased placental Ca 2+ transfer, as has been observed in mice 45, 46. Because bone mineralization normalizes by 2 years in these infants, humans also appear to compensate for the loss of TRPV6 in early development.…”