Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring
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Published:2024-01-16
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ISSN:1469-3178
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Container-title:EMBO Reports
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language:en
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Short-container-title:EMBO Rep
Author:
Correa Pinto Junior Danilo, Canal Delgado Isabella, Yang HaiyangORCID, Clemenceau Alisson, Corvelo AndréORCID, Narzisi Giuseppe, Musunuri RajeevaORCID, Meyer Berger Julian, Hendricks Lauren E, Tokumura Kazuya, Luo Na, Li Hongchao, Oury FranckORCID, Ducy PatriciaORCID, Yadav Vijay KORCID, Li XiangORCID, Karsenty GerardORCID
Abstract
AbstractMany physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.
Funder
HHS | NIH | National Institute on Aging HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development Shenzhen Science and Technology Program
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Molecular Biology,Biochemistry
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