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Maternal smoking during pregnancy aggravated muscle phenotype in FHL1 -/y offspring mice similar to congenital clubfoot through P2RX7-mediated pyroptosis.
- Source :
-
Toxicology letters [Toxicol Lett] 2021 Jul 01; Vol. 345, pp. 54-60. Date of Electronic Publication: 2021 Apr 16. - Publication Year :
- 2021
-
Abstract
- Congenital clubfoot (CCF) is a common birth defect. Maternal smoking during pregnancy increases the risk of CCF. In previous research, we found muscle phenotypes similar to CCF in four and a half LIM domain protein 1 (FHLI) offspring mice (FHL1 <superscript>-/y</superscript> ). However, the role of P2RX7-mediated pyroptosis in the effect of cigarette smoke (CS) on the skeletal muscle of FHL1 <superscript>-/y</superscript> mice during pregnancy is unclear. In the present study, pregnant mice at 11 days of gestation were exposed to CS and male offspring of wild-type (WT) and FHL1 <superscript>-/y</superscript> mice were divided into four groups (Control-WT, Control-KO, CS-WT, CS-KO). The histomorphology of lower limb muscles was examined using hematoxylin and eosin (H&E) staining. P2RX7, indicators of pyroptosis (NLRP3, ASC, cleaved-caspase 1, IL-1β), and cytoskeletal proteins (MYBPC2, LDB3) were also detected using immunoblotting. CS exposure during pregnancy aggravated the muscle phenotype similar to CCF in FHL1 <superscript>-/y</superscript> offspring mice. FHL1 gene knockout (KO) or CS exposure during pregnancy each activated the expression of P2RX7, cell pyroptosis-related proteins (NLRP3, ASC, cleaved-caspase 1, IL-1β), a muscle injury marker (MYOD1), and cytoskeletal proteins (MYBPC2, LDB3); these two factors had an additive effect. The results showed maternal smoking during pregnancy aggravated muscle phenotype similar to CCF in FHL1 <superscript>-/y</superscript> offspring mice through P2RX7-mediated pyroptosis.<br />Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Animals
Carrier Proteins metabolism
Clubfoot genetics
Clubfoot pathology
Female
Gestational Age
Intracellular Signaling Peptides and Proteins genetics
LIM Domain Proteins genetics
LIM Domain Proteins metabolism
Male
Maternal Exposure adverse effects
Mice, Inbred C57BL
Mice, Knockout
Muscle Proteins genetics
Muscle, Skeletal pathology
MyoD Protein metabolism
Phenotype
Pregnancy
Pyroptosis
Signal Transduction
Mice
Clubfoot metabolism
Intracellular Signaling Peptides and Proteins deficiency
LIM Domain Proteins deficiency
Muscle Proteins deficiency
Muscle, Skeletal metabolism
Prenatal Exposure Delayed Effects
Receptors, Purinergic P2X7 metabolism
Smoking adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 345
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 33872746
- Full Text :
- https://doi.org/10.1016/j.toxlet.2021.04.014