Figure 3.

The mechanisms through which statin may impact male fertility. (a). Cholesterol bioavailability in a Leydig cell; (b). Testosterone synthesis in a Leydig cell; (c) Routes through which statins affect male reproduction. The Leydig cell can absorb cholesterol from the blood via low density lipoprotein- receptors (LDL-R) and are also capable of de novo cholesterol synthesis. The de novo synthesis of cholesterol starts with pyruvate being generated from diverse cytosolic sources. Entry of pyruvate into the mitochondrial matrix is mediated by the mitochondrial pyruvate carrier (MPC). In the matrix, pyruvate is converted into acetyl CoA or oxaloacetate by pyruvate dehydrogenase (PDH). The acetyl CoA produced is converted to citric acid outside the matrix. Upon the initiation of statin metabolism, there is a decrease in the circulating LDL-cholesterol and the total amount of cholesterol transported to the Leydig cell is reduced. Additionally, the incapability of the LDL-R to aid the transport into the Leydig cell will further tamper with the bioavailability of cholesterol in these cells, thus making the Ledig cell solely dependent on the de novo synthesis of cholesterol. Since the unretained statins are redistributed to other organs including the testes, then, it is possible that the de novo cholesterol synthesis is also inhibited. Hence, there will be little or no bioavailability of cholesterol for testosterone synthesis. Subsequently, the lack of or decrease in testosterone will lead to male sexual dysfunctions and altered reproductive parameters. TSPO (mitochondrial translocator protein 18); STAR (cytosolic steroidogenic acute regulatory protein); STARD1 (START domain-containing 1); ACBD3 (acyl-coenzyme A binding domain-containing 3); CYP11A1 (cytochrome p450 family 11 subfamily A polypeptide 1); MPC (mitochondrial pyruvate carrier); LH-R (luteinizing hormone receptor); PDH (pyruvate dehydrogenase); and HMG-CoA (3 hydro 3 methyl glutaryl co enzyme A).