TY - JOUR
T1 - Maternal Gut Microbiome Decelerates Fetal Endochondral Bone Formation by Inducing Inflammatory Reaction
AU - Uchida-Fukuhara, Yoko
AU - Hattori, Takako
AU - Fu, Shanqi
AU - Kondo, Sei
AU - Kuwahara, Miho
AU - Fukuhara, Daiki
AU - Islam, Md Monirul
AU - Kataoka, Kota
AU - Ekuni, Daisuke
AU - Kubota, Satoshi
AU - Morita, Manabu
AU - Iikegame, Mika
AU - Okamura, Hirohiko
N1 - Funding Information:
Funding: This work was supported by JSPS KAKENHI Grant Number JP18K17282.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5
Y1 - 2022/5
N2 - To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses’ whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta.
AB - To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses’ whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta.
KW - endochondral ossification
KW - fetal chondrocytes
KW - maternal microbiome
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U2 - 10.3390/microorganisms10051000
DO - 10.3390/microorganisms10051000
M3 - Article
AN - SCOPUS:85129587563
SN - 2076-2607
VL - 10
JO - Microorganisms
JF - Microorganisms
IS - 5
M1 - 1000
ER -