Computer assisted semen analyzers in andrology research and veterinary practice

BACKGROUND: Sperm hyperactivation is critical to fertilization, because it is required for penetration of the zona pellucida. Hyperactivation may also facilitate release of sperm from the oviductal storage reservoir and may propel sperm through mucus in the oviductal lumen and the matrix of the cumulus oophorus. Hyperactivation is characterized by high amplitude, asymmetrical flagellar bending. METHODS: This is a review of the original literature on the mechanisms that regulate hyperactivation, including physiological factors and signaling pathways. RESULTS: Computer-assisted semen analysis systems can be used to identify hyperactivated sperm by setting minimum thresholds for curvilinear velocity (VSL) and lateral head movement and a maximum threshold for path linearity. Hyperactivation is triggered by a rise in flagellar Ca(2+) resulting from influx primarily through plasma membrane CatSper channels and possibly also by release of Ca(2+) from a store in the redundant nuclear envelope. It requires increased pH and ATP production. The physiological signals that trigger the rise in Ca(2+) remain elusive, but there is evidence that the increased Ca(2+) acts through a calmodulin/calmodulin kinase pathway. Hyperactivation is considered part of the capacitation process; however, the regulatory pathway that triggers hyperactivation can operate independently from that which prepares sperm to undergo the acrosome reaction. Hyperactivation may be modulated by chemotactic signals to turn sperm toward the oocyte. CONCLUSIONS: Little is known about exactly what triggers hyperactivation in human sperm. This information could enable clinicians to develop reliable fertility assays to assess normal hyperactivation in human sperm samples.

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Control of hyperactivation in sperm

The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily members are found in a remarkable range of organisms spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33 individual family members, respectively, and although many are poorly characterized, the majority show a notable expression bias to the reproductive tract and immune tissues or are deregulated in cancers. CAP superfamily proteins are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumor suppressor or prooncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. This review describes mammalian CAP superfamily gene expression profiles, phylogenetic relationships, protein structural properties, and biological functions, and it draws into focus their potential role in health and disease. The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. We conclude that overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters target specificity and, therefore, the biological consequences.

The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins—Roles in Reproduction, Cancer, and Immune Defense

Human sperm hyperactivation and capacitation as parts of an oxidative process.

The identification of human sperm hyperactivated motility has potential importance in sperm function tests, as well as in quality control assays and in reproductive toxicology investigations. However, relatively little is known about this phenomenon and the variety of definitions used for hyperactivation has led to a great deal of confusion as to its occurrence and physiological relevance. This presentation is a critical review of a number of aspects of hyperactivated motility, including its identification and potential role(s) in mammalian fertilization. The initial sections of the review consider the mechanisms involved in the development and maintenance of mammalian sperm motility, and the structural and functional changes in spermatozoa which occur during transport through the female reproductive tract. The methods available for the quantification of aspects of sperm movement are also discussed, with an historical overview of sperm movement analysis.

/pdf/a-critical-review-of-the-physiological-importance-and-24713rvrib.pdf

A critical review of the physiological importance and analysis of sperm movement in mammals

Suspensions of capacitating human spermatozoa were analyzed for potential hyperactivated movements using videomicrographic methods. Analysis was carried out on aliquots of 22 sperm suspensions, which were proved fertile several hours later during human in vitro fertilization. After approximately 3 h of capacitation, 22.1% of the fertile spermatozoa displayed motility patterns designated as hyperactivated. Over 80% of these hyperactivated spermatozoa moved with a wide-amplitude, two-dimensional whiplash pattern, displaying marked lateral displacement of the head. Only 8.4% of capacitating spermatozoa from oligozoospermic patients showed these hyperactivated movements. The incidence of hyperactivated movements by fertile and oligozoospermic spermatozoa could be significantly increased after exposure to various motility stimulants. The clinical significance of hyperactivation as a functional assay of fertilizing capacity is discussed.

https://www.tandfonline.com/doi/pdf/10.3109/01485018408987514

Lani Johnson Burkman

Papers

Characterization of hyperactivated motility by human spermatozoa during capacitation: comparison of fertile and oligozoospermic sperm populations.