Effects of L-Carnitine on the sperm parameters disorders, apoptosis of spermatogenic cells and testis histopathology in diabetic Rats

Abstract

Background: Diabetes mellitus affects male reproductive system that is known to cause male infertility.
 Objective: The aim of the present study was to assess the effects of L-carnitine (LC) on sperm parameters, apoptosis of spermatogenic cells and testis histopathology in Streptozotocin-induced diabetic Rats.
 Materials and Methods: The study was carried out on 36 male Wistar adult rats (220 ± 30 gr) randomly divided into six groups (n = 6/each). 1 (Control); 2 (LC 100 mg/kg); 3 (Diabetic); 4, 5, and 6 (Diabetic + LC 50 or 100 or 200 mg/kg, respectively). Daily injections were administered intraperitoneally for 48 days. Then, rats were sacrificed, left testis and epididymis were harvested for sperm analysis and histopathology, morphometric and spermatogenesis assessments, and Tunnel assay.
 Results: L-carnitine in group 6 significantly decreased blood glucose level (p < 0.01) in comparison with group 3. L-carnitine in groups 5 and 6 significantly (p < 0.001) and dose-dependently increased the count, motility, viability, maturity, and chromatin quality of sperm and decreased the abnormal morphology of sperm in comparison with group 3. In groups 4, 5, and particularly 6, in comparison with group 3, there has been a significant difference in the increase of seminiferous tubule diameter, germinal epithelium height (p < 0.001), maturity quality of the seminiferous tubules (p < 0.001), decrease apoptosis of spermatogenic cells (p < 0.001), and testis tissue histopathological complications.
 Conclusion: The data obtained from the present study suggest that in the diabetic rats, LC decreases serum glucose level, improves the diameter and thickness of the epithelium of spermatogenic cells, reduces germ cells’ apoptosis, and improves epididymal sperm parameters. Therefore, it seems that LC plays an effective role in diabetes-induced infertility.

Dietary L‐carnitine affects the expression of genes involved in apoptosis and fatty acid metabolism in rooster testes

“…Therefore, our findings support the hypothesis that the support- Apoptosis is mediated by a group of highly specific cysteine proteases known as cysteine aspartic acid-specific proteases (caspases family) (Shalini et al, 2015). Recently, Mardanshahi et al, 2019 showed that LC consumption by diabetic rats can inhibit the activity of caspases and prevent apoptosis. Oxidative stress is a principal regulator of apoptosis which can be induced by two main pathways: the internal pathway that involves binding of TNF-α and Fas ligand to membrane receptors leading to caspase-8 activation, and the external pathway that takes part in stress-induced mitochondrial cytochrome c release (Westphal et al, 2014).…”

“…Recently, it was indicated that mice fed with LC showed increased PGC1α levels in the testis, which probably regulates steroidogenesis by increasing Bcl2 mRNA abundance (Roy et al, 2017). Also, it was reported that LC effectively prevents apoptosis by carrying the accumulated long chain fatty acid surrounding mitochondria in testes of diabetic rats (Mardanshahi et al, 2019). The testis is an extraordinary organ with respect to fatty acid metabolism (Saito & Aono, 2014), and spermatozoa contain polyunsaturated fatty acids (PUFA) of diverse nature conforming to the species (Brinsko et al, 2005).…”

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

“…Along with MF monotherapy, the combinations of MF with different natural antioxidants, including honey [ 463 ] and Malaysian propolis [ 453 , 464 ], restored the testicular function and hormonal parameters of the male HPG axis in diabetic animals. Some compounds with antioxidant and antiapoptotic activity, but different from MF molecular mechanisms, for example, l -carnitine, may be effective [ 465 ]. There is a question in this regard, for which mechanisms determine the antioxidant and antiapoptotic effects of MF and its restorative effect on spermatogenesis and testicular steroidogenesis?…”

Effects of L-carnitine combined with pancreatic kininogenase on thioredoxin 2, thioredoxin reductase 1, and sperm quality in patients with oligoasthenospermia

“…LC is mainly distributed in blood and tissues, among which the epididymis has the highest concentration, although it is not synthesized here (11). Studies have shown that when sperm move from the head to the tail of the epididymis, LC can reduce lipid content on the sperm membrane, and increase the ratio of saturated fatty acids, unsaturated fatty acids, cholesterol, and congealed fat, causing changes in membrane composition and structure and maintaining fluidity of the sperm membrane (7). Other reports have shown that LC has an antioxidant effect, can inhibit the production of reactive oxygen species, avoid sperm oxidative damage, and effectively maintain the normal physiological function of sperm (12,13).…”

“…L-carnitine (LC) is the only carrier for the transport of long-chain fatty acids into the mitochondrial inner membrane for β-oxidation, promoting oxidation reaction and providing energy for cells (6). LC also regulates testicular supporting cells, removing oxygen free radicals in seminal plasma, reducing sperm aggregation, and reducing spermatogenic cell apoptosis (6,7). At present, many hospitals regard LC as the preferred drug for the treatment of male infertility syndrome (8).…”