The human sperm proteome-Toward a panel for male fertility testing

Although male factor accounts for 40%-50% of unintended childlessness, we are far from fully understanding the detailed causes. Usually, affected men cannot even be provided with a molecular diagnosis.

We aimed at a higher resolution of the human sperm proteome for better understanding of the molecular causes of male infertility. We were particularly interested in why reduced sperm count decreases fertility despite many normal-looking spermatozoa and which proteins might be involved.

Applying mass spectrometry analysis, we qualitatively and quantitatively examined the proteomic profiles of spermatozoa from 76 men differing in fertility. Infertile men had abnormal semen parameters and were involuntarily childless. Fertile subjects exhibited normozoospermia and had fathered children without medical assistance.

We discovered proteins from about 7000 coding genes in the human sperm proteome. These were mainly known for involvements in cellular motility, response to stimuli, adhesion, and reproduction. Numbers of sperm proteins showing at least threefold deviating abundances increased from oligozoospermia (N = 153) and oligoasthenozoospermia (N = 154) to oligoasthenoteratozoospermia (N = 368). Deregulated sperm proteins primarily engaged in flagellar assembly and sperm motility, fertilization, and male gametogenesis. Most of these participated in a larger network of male infertility genes and proteins.

We expose 31 sperm proteins displaying deviant abundances under infertility, which already were known before to have fertility relevance, including ACTL9, CCIN, CFAP47, CFAP65, CFAP251 (WDR66), DNAH1, and SPEM1. We propose 18 additional sperm proteins with at least eightfold differential abundance for further testing of their diagnostic potential, such as C2orf16, CYLC1, SPATA31E1, SPATA31D1, SPATA48, EFHB (CFAP21), and FAM161A.

Our results shed light on the molecular background of the dysfunctionality of the fewer spermatozoa produced in oligozoospermia and syndromes including it. The male infertility network presented may prove useful in further elucidating the molecular mechanism of male infertility.