Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia
Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the s...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1067683/full |
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| author | Wirongrong Wongkitikamjorn Wirongrong Wongkitikamjorn Eiji Wada Jun Hosomichi Hideyuki Maeda Sirichom Satrawaha Haixin Hong Haixin Hong Ken-ichi Yoshida Takashi Ono Yukiko K. Hayashi |
| author_facet | Wirongrong Wongkitikamjorn Wirongrong Wongkitikamjorn Eiji Wada Jun Hosomichi Hideyuki Maeda Sirichom Satrawaha Haixin Hong Haixin Hong Ken-ichi Yoshida Takashi Ono Yukiko K. Hayashi |
| author_sort | Wirongrong Wongkitikamjorn |
| collection | DOAJ |
| description | Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats. |
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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-10T23:29:45Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-4fd564fbabdf48bba2a1cdaf8fc7c5a72023-01-12T07:01:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-01-011410.3389/fphys.2023.10676831067683Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxiaWirongrong Wongkitikamjorn0Wirongrong Wongkitikamjorn1Eiji Wada2Jun Hosomichi3Hideyuki Maeda4Sirichom Satrawaha5Haixin Hong6Haixin Hong7Ken-ichi Yoshida8Takashi Ono9Yukiko K. Hayashi10Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, ThailandDepartment of Pathophysiology, Tokyo Medical University, Tokyo, JapanDepartment of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Forensic Medicine, Tokyo Medical University, Tokyo, JapanDepartment of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, ThailandDepartment of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Stomatology, Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Forensic Medicine, Tokyo Medical University, Tokyo, JapanDepartment of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Pathophysiology, Tokyo Medical University, Tokyo, JapanGestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.https://www.frontiersin.org/articles/10.3389/fphys.2023.1067683/fullgestational intermittent hypoxiaskeletal muscledevelopmental origins of health and disease (DOHaD)energy metabolismadiponectin receptorscapillarization |
| spellingShingle | Wirongrong Wongkitikamjorn Wirongrong Wongkitikamjorn Eiji Wada Jun Hosomichi Hideyuki Maeda Sirichom Satrawaha Haixin Hong Haixin Hong Ken-ichi Yoshida Takashi Ono Yukiko K. Hayashi Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia Frontiers in Physiology gestational intermittent hypoxia skeletal muscle developmental origins of health and disease (DOHaD) energy metabolism adiponectin receptors capillarization |
| title | Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia |
| title_full | Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia |
| title_fullStr | Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia |
| title_full_unstemmed | Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia |
| title_short | Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia |
| title_sort | metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia |
| topic | gestational intermittent hypoxia skeletal muscle developmental origins of health and disease (DOHaD) energy metabolism adiponectin receptors capillarization |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1067683/full |
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