Maternal rodent exposure to di‐(2‐ethylhexyl) phthalate decreases muscle mass in the offspring by increasing myostatin

Autor: Fengju Li, Ting Luo, Honghui Rong, Lu Lu, Ling Zhang, Chuanfeng Zheng, Dali Yi, Yi Peng, Enyu Lei, Xiaotao Xiong, Fengchao Wang, Jose M. Garcia, Ji‐an Chen
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 13, Iss 6, Pp 2740-2751 (2022)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13098
Popis: Abstract Background Di‐(2‐ethylhexyl) phthalate (DEHP) and its metabolites can cross the placenta and may cause birth defects and developmental disorders. However, whether maternal DEHP exposure affects skeletal muscle development in the offspring and the pathways involved are unknown. This study investigated the effects of maternal DEHP exposure and the contribution of myostatin (MSTN) to skeletal muscle development in the offspring. Methods Pregnant wild‐type and muscle‐specific myostatin knockout (MSTN KO) C57BL/6 mice were randomized to receive vehicle (corn oil) or 250 mg/kg DEHP by gavage every other day until their pups were weaned (postnatal day 21 [PND21]). Body weights of the offspring mice were measured longitudinally, and their hindleg muscles were harvested at PD21. Also, C2C12 cells were treated with mono‐2‐ethylhexyl phthalate (MEHP), the primary metabolite of DEHP, and proteolysis, protein synthesis, and myogenesis markers were measured. The contribution of myostatin to maternal DEHP exposure‐induced muscle wasting in the offspring was determined. Results Maternal DEHP exposure reduced body weight growth, myofibre size, and muscle mass in the offspring compared to controls (Quad: 2.70 ± 0.1 vs. 3.38 ± 0.23, Gastroc: 2.29 ± 0.09 vs. 2.81 ± 0.14, Tibialis: 1.01 ± 0.07 vs. 1.25 ± 0.11, mg/tibial length in mm, all P 0.05, n = 5). In vitro, C/EBPδ silencing abrogated the MEHP‐induced increases in Myostatin, MuRF‐1, and Atrogin‐1 and decreases in MyoD and Myogenin expression. Conclusions Maternal DEHP exposure impairs skeletal muscle development in the offspring by enhancing the C/EBPδ‐myostatin pathway in mice.
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