Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice

Background: Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. Methods: Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed. Results: In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 +/- 12.31 ng/g vs. 74.10 +/- 11.45 ng/g, P = 0.027; sperm number: [14.94 +/- 4.63] x 10(6) cells/ml vs. [8.79 +/- 4.38] x 10(6) cells/ml, P = 0.002; sperm motility: 43.16 +/- 9.93% vs. 33.51 +/- 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 +/- 11.01 ng/ml vs. 49.30 +/- 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 +/- 0.09 vs. 0.84 +/- 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 +/- 8.67, P = 0.005; sperm number: [4.34 +/- 2.45] x 10(6) cells/ml, P = 0.018; sperm motility: 19.53 +/- 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 +/- 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 +/- 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 +/- 0.09, P < 0.001), and fertility was also suppressed (P < 0.05, respectively). Conclusion: SKRBT had no adverse effect on fertility potential in aging male mice.