Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats
Corresponding Author
Kevin Silva Muller BSc
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Graduate Program in Surgery and Translational Medicine, São Paulo State University, Medical School, Botucatu, Brazil
Correspondence
Kevin Silva Muller, Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University, Rua Professor Doutor Antonio Celso Wagner Zanin, 250, Unesp Campus de Botucatu, Botucatu, São Paulo, Brazil.
Email: [email protected]
Search for more papers by this authorFelipe Cantore Tibúrcio MSc
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Graduate Program in Surgery and Translational Medicine, São Paulo State University, Medical School, Botucatu, Brazil
Search for more papers by this authorJorge Willian Franco de Barros MSc
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Search for more papers by this authorCintia Yuri Matsumura PhD
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Search for more papers by this authorSelma Maria Michelin Matheus PhD
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Graduate Program in Surgery and Translational Medicine, São Paulo State University, Medical School, Botucatu, Brazil
Search for more papers by this authorCorresponding Author
Kevin Silva Muller BSc
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Graduate Program in Surgery and Translational Medicine, São Paulo State University, Medical School, Botucatu, Brazil
Correspondence
Kevin Silva Muller, Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University, Rua Professor Doutor Antonio Celso Wagner Zanin, 250, Unesp Campus de Botucatu, Botucatu, São Paulo, Brazil.
Email: [email protected]
Search for more papers by this authorFelipe Cantore Tibúrcio MSc
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Graduate Program in Surgery and Translational Medicine, São Paulo State University, Medical School, Botucatu, Brazil
Search for more papers by this authorJorge Willian Franco de Barros MSc
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Search for more papers by this authorCintia Yuri Matsumura PhD
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Search for more papers by this authorSelma Maria Michelin Matheus PhD
Division of Anatomy, Department of Structural and Functional Biology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil
Graduate Program in Surgery and Translational Medicine, São Paulo State University, Medical School, Botucatu, Brazil
Search for more papers by this authorAbstract
Introduction/Aims
The mechanisms that underlie the pathogenesis of statin-associated muscle symptoms (SAMS) remain unclear. Pregnancy is associated with increased cholesterol levels. Statins may be useful during pregnancy, but their safety is uncertain. Hence, we investigated the postpartum effects of exposure to rosuvastatin and simvastatin during pregnancy in Wistar rats, targeting the neuromuscular structures.
Methods
Twenty-one pregnant Wistar rats were divided into three groups: control (C) treated with vehicle (dimethylsulfoxide + dH20), simvastatin (S) 62.5 mg/kg/day, and rosuvastatin (R) 10 mg/kg/day. Gavage was performed daily from the gestational days 8 to 20. At weaning, the postpartum mother tissues were collected and subjected to morphological and morphometric analysis of the soleus muscle, associated neuromuscular junctions (NMJs), and the sciatic nerve; protein quantification; quantification of the cholesterol and creatine kinase in the serum; and intramuscular collagen analysis.
Results
An increase in morphometric parameters (area, maximum and minimum diameters, Feret diameter, and minimum Feret) was observed in NMJs from the S and R groups in comparison with the C group, and there was also a loss of common NMJ circularity. The number of myofibers with central nuclei was higher in S (17 ± 3.9, P = .0083) and R (18.86 ± 14.42, P = .0498) than in C (6.8 ± 2.6).
Discussion
Gestational exposure to statins induced postpartum NMJ morphology alterations in soleus muscle, which may be caused by the remodeling of clusters of nicotinic acetylcholine receptors. This may be associated with the development and progression of SAMS observed in clinical practice.
CONFLICT OF INTEREST STATEMENT
None of the authors has any conflict of interest to disclose.
Open Research
DATA AVAILABILITY STATEMENT
The datasets generated or analyzed during the current study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| mus27825-sup-0001-FigureS1.jpgimage/jpp, 104.7 KB | FIGURE S1. Graphical representation of the experimental design used in this study. Abbreviations: GD, gestational day; PPD, postpartum day. |
| mus27825-sup-0002-FigureS2.jpgimage/jpp, 155.5 KB | FIGURE S2. Whole uncut blot of the analyzed proteins: (A) glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression used for epsilon normalization; (B) epsilon expression; (C) GAPDH expression used for alpha1 normalization; (D) alpha1 expression; (E) GAPDH expression used for gapsyn, MuSK, and gamma normalization; (F) rapsyn expression; (G) muscle-specific kinase expression; and (H) gamma expression. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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