Statin exposure during pregnancy promotes neuromuscular junction alterations in post-partum Wistar rats.

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 post-partum 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 8th to the 20th gestational day. At weaning, the post-partum 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 diameter, 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 = 0.0083) and R (18.86 ± 14.42 p = 0.0498) than in C (6.8 ± 2.6).

DISCUSSION: Gestational exposure to statins induced post-partum 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. This article is protected by copyright. All rights reserved.