Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

Abstract

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.

Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats

“…However, morphometric analysis showed an increase in the maximum diameter in the animals that underwent physical exercise compared to the sedentary animals. NMJs are highly plastic structures, whose diameter can remodel rapidly in response to different stimuli, including denervation [45][46][47][48], aging [33], or drug therapies [49]. Primary alterations in the NMJ can directly generate a functional loss in several diseases, resulting in skeletal muscle weakness and increased fatigue [50].…”