Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.
Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.
复制标题
母体和胚胎来源的骨钙素协同作用，在后代中建立体内平衡。
DOI：
10.1038/s44319-023-00031-3
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发表时间：
2024
期刊：
影响因子：
7.7
通讯作者：
Ducy,Patrici
中科院分区：
文献类型：
--
作者：
CorreaPintoJunior,Danilo;CanalDelgado,Isabella;Yang,Haiyang;Clemenceau,Alisson;Corvelo,André;Narzisi,Giuseppe;Musunuri,Rajeeva;MeyerBerger,Julian;Hendricks,LaurenE;Tokumura,Kazuya;Luo,Na;Li,Hongchao;Oury,Franck;Ducy,Patrici
在经历了不健康怀孕的母亲的成年后代中，许多生理上的骨钙素调节功能受到影响。此外，妊娠期间的骨钙素信号影响成年小鼠的认知和肾上腺类固醇激素的生成。总之，这些观察表明，骨钙素可能在怀孕期间广泛发挥作用，以确定成年哺乳动物的机体内环境平衡。为了验证这一假设，我们分析了未受挑战的野生型和骨钙素缺乏、不同基因类型和来源的不同遗传背景的新生和成年小鼠，骨钙素在胰腺、肝脏和睾丸中的功能及其分子基础。这项分析显示，提供母亲的骨钙素缺乏，胚胎中的骨钙素单倍体不足会阻碍成年后代的胰岛素分泌、肝脏糖异生、葡萄糖稳态、睾丸类固醇生成；抑制发育中的胰岛和睾丸的细胞增殖；并扰乱这些器官和大脑中不同的基因表达程序。这项研究表明，骨钙素在其影响的大多数器官中发挥主导作用。此外，母体和胚胎来源的骨钙素通过对多种生理功能的协同调节，有助于建立和维持新生儿和成年后代的机体内环境平衡。
Many 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 andOsteocalcin-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 areOsteocalcin-deficient,Osteocalcinhaploinsufficiency 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 thatosteocalcinexerts 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.