Influence of all‐trans retinoic acid on sperm metabolism and oxidative stress: Its involvement in the physiopathology of varicocele‐associated male infertility

Abstract

The mechanisms by which varicocele affects fertility remain undetermined. Vitamin A (all-trans retinoic acid [ATRA]) is required for fertility and normal spermatogenesis; however, the mechanisms driving its action are not defined yet. Previously, we demonstrated in varicocele sperm a reduced RARα expression and that ATRA influence sperm performance. To further define vitamin A significance in male gamete and in the physiopathology of varicocele, we tested for the first time ATRA action on human sperm metabolism and antioxidant defense systems. Evaluating triglycerides content and lipase activity, in normal sperm ATRA had a lipid lowering effect, which was not observed in varicocele sperm. The modulation of the glucose-6-phosphate dehydrogenase activity, concomitantly with a reduction of the glucose content, highlight an ATRA role on glucose metabolism. ATRA induced the superoxide dismutase (SOD) and glutathione transferase activities, while it reduced the malondialdehyde and reactive oxygen species (ROS) production both in healthy and varicocele sperm. Interestingly, SOD1 and SOD2 have been localized in the acrosome and midpiece, glutathione- S-transferase omega 2 (GSTO2) in the acrosome, equatorial, and subacrosomial regions. SOD1, SOD2, and GSTO2 levels were significantly lower in varicocele with respect to healthy sperm. Herein, we discovered that ATRA treatment was able to reprogram sperm metabolism toward that of the capacitation status. The retinol protected human sperm from ROS damage enhancing the antioxidant enzymes activity, providing evidence toward the efficacy of vitamin A as therapeutic tool in improving sperm quality. These novel findings further confirm the importance of vitamin A in male fertility adding new insights into the retinoids complex biological framework.

Varicocoele and oxidative stress: New perspectives from animal and human studies

“…Although the antioxidant ingredients, dosages, duration of treatment, and parameters measured differed significantly from one study to another, major improvements were observed including a favorable effect on spermatogenesis, sperm count, motility, morphology and integrity of sperm DNA, enzymatic and non‐enzymatic antioxidant status of testicular tissue, and gonadotropin and testosterone levels 24,25,31‐34 . Antioxidant supplementation has also been the subject of several studies in VCL patients 31,32,35‐37 . Here too, despite the great heterogeneity between clinical studies, beneficial effects were notable.…”

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

“…The bone marrow lipid composition does not strictly depend only on lipids dietary intakes and may act in bone homeostasis as a key regulator. Palmitic and stearic saturated fatty acids may result in being lipotoxic to bone [206,207] and impair the OBL physiology [208,209], whereas palmitoleic, oleic, and linoleic unsaturated fatty acids seem to promote OBL differentiation, survival, and mineralization activity [206,209,210], while inhibiting OCL both differentiation and function [211,212]. Considering the association with bone fragility [213,214], it has been suggested that bone marrow saturated index, the proportion of saturated fatty acids to total fatty acids, to be a potential biomarker for osteoporosis [215].…”

Role of Antioxidants in Alleviating Bisphenol A Toxicity

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