A lab test showed that the peptide thymosin‑alpha‑1 can boost human sperm’s ability to penetrate an egg‑like target, especially at a specific low dose, and that a short version of the peptide (the last 14 building blocks) works almost as well. This points to a possible new way to help men with fertility issues, but the research is still early and done in a test‑tube, not in people.

Thymosin-alpha 1 (T alpha 1) and six T alpha 1 analogs were synthesized to study structure-function relationships and to search for the biologically active and stable epitope(s) that would have clinical application in the treatment of male infertility. Four of these analogs were prepared by modification/substitution of N- and C-terminal amino acids of T alpha 1 peptide, and the other two analogs were fragments having only N-16 amino acids (N-terminal) or C-14 amino acids (C-terminal), respectively, of the T alpha 1 peptide. T alpha 1 and these six analogs were tested for their effects on human sperm penetration rates in the sperm penetration assay (SPA). T alpha 1 significantly (p < .0001) increased the penetration rates in SPA, with the strongest enhancing effect at 0.5 microgram/100 microL concentration. Of the six analogs tested only two, T alpha 1-Gly-NH2 and T alpha 1-C14, retained the enhancing effects in SPA. None of the analogs decreased the penetration rates or affected sperm motility compared to control. The enhancing activity resides primarily in an epitope, the C-terminal 14 amino acids of T alpha 1. However, for maximal effect both N- and C-terminal amino acids (serine and asparagine, respectively) have to be intact and unmodified. The T alpha 1-Gly-NH2 analog that had its C-terminal protected was as potent as the intact T alpha 1 peptide. T alpha 1 and this analog may have clinical applications in treatment of male-factor-mediated infertility.