Control of APN/CD13 and NEP/CD10 on sperm motility

Abstract

Aminopeptidase N (APN/CD13) and neutral endopeptidase (NEP/CD10) are enzymes present in human sperm cells and involved in regulation of sperm motility of noncapacitated spermatozoa. We investigated the involvement of APN/CD13 and NEP/CD10 in motility and in kinematic parameters of human capacitated spermatozoa. Sperm cells isolated by a discontinuous Percoll gradient (40%-80%) followed up by swim-up techniques were incubated with the APN/CD13-specific inhibitor, leuhistin (100 µmol L -1 ), and the NEP/CD10-specific inhibitor, thiorphan (1 µmol L -1 ). The complete inhibition of both APN/CD13 and NEP/CD10 improved sperm motility. Spermatozoa incubated with the APN/CD13-specific inhibitor leuhistin showed asymmetrical trajectories, whereas sperm trajectories were more regular after treatment with the NEP/CD10-specific inhibitor thiorphan. In conclusion, APN/CD13 and NEP/CD10 modulate the motility of capacitated spermatozoa, although each of the enzymes seems to participate in the control of different aspects of sperm motility. Therefore, both inhibitors may be useful for sperm activation at different functional stages of spermatozoa.

Peptides in Seminal Fluid and Their Role in Infertility: A Potential Role for Opiorphin Inhibition of Neutral Endopeptidase Activity as a Clinically Relevant Modulator of Sperm Motility: A Review

“…Although sperm morphology, motility, and total concentration are hypothesized to have the strongest correlation with successful pregnancy, [5][6][7][8] sperm motility may be the most reliable predictor of male factor infertility. [10][11][12] Consistent with this hypothesis, a prospective study designed to evaluate sperm characteristics and the likelihood of pregnancy in infertile couples reported sperm motility and the mean number of morphological abnormalities observed per abnormal spermatozoa (multiple anomalies index) were the best prognostic factors in couples diagnosed with primary infertility. In contrast, age of the male partner and percentage of normal sperm were the best prognostic factors for pregnancy in groups with secondary infertility.…”

“…However, each enzyme appears to control different aspects of sperm motility. 10 For example, APN activity is increased in men with asthenozoospermia or necrozoospermia. 17 Subiran et al recently reported that both APN and NEP adversely affect motility as well as the trajectory of human capacitated spermatozoa.…”

“…10 Both APN and NEP modulate motility of capacitated spermatozoa. However, each enzyme appears to control different aspects of sperm motility.…”

“…The clinical relevance of these motility semen parameter changes relate to evidence that suggests hyperactivation is necessary for fertilization, and progressive motility is necessary for movement through the female reproductive tract. 10,18 Another group of peptides found in seminal plasma that may affect sperm motility include kinins, mainly bradykinin (BK), and other components of the kallikrein-kinin system. Siems et al reported that BK significantly increased sperm motility when used at subnanomolar concentrations.…”

“…[2][3][4]10,[15][16][17][18][19][20] Although it is recognized that seminal peptides affect sperm motility, the precise role of individual peptides is minimally understood. The rapidly growing number of peptides identified in the seminal plasma peptidome introduces an additional level of challenge for researchers interested in characterizing the role of individual seminal proteins in male fertility.…”