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Sperm Testing and ICSI Selection by Hyaluronic Acid Binding: The Hyaluronic Acid-Coated Glass Slide and Petri Dish in the Andrology and IVF Laboratories

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Abstract

It is well established that the testis-expressed HspA2 chaperone is a measure of human sperm cellular maturity and function, including fertilizing potential. The presence of HspA2 in the synaptonemal complex also provides the link between low HspA2 expression and increased frequencies of chromosomal aneuploidies in arrested maturity, dysmature sperm. There is also a relationship between the levels of HspA2 expression in elongated spermatids and the related spermiogenetic events, such as cytoplasmic extrusion, formation of the normal sperm shape, the nuclear events of histone-transition protein-protamine replacement, and the associated changes in DNA packing, as well as the sperm plasma membrane remodeling. The membrane remodeling facilitates the formation of the zona pellucida (and the hyaluronic acid [HA]) binding sites, which enables the sperm to fertilize and provide paternal contribution to the embryo. In dysmature sperm, some or all of these developmental steps are arrested (there is a well-established relationship between nuclear and cytoplasmic dysmaturity). For this reason, the sperm selected by the zona pellucida or by hyaluronic acid are comparable via the common origin of plasma membrane remodeling and the formation of both receptors. With the advent of ICSI, the challenge to understand which sperm is empowered to fertilize the egg and the ongoing research focusing on biochemical markers of sperm function have taken higher prominence, as the pathology in male infertility patients, who require ICSI treatment, of higher complexity. The HA receptor of mature sperm, coupled with HA-coated slides or Petri dishes, allows the direct visual observation of sperm-HA binding, which is the basis for sperm maturity testing, and the assessment of sperm binding to HA which is related to sperm-zona pellucida binding. Sperm-Ha binding provides a major advancement in semen evaluation and it also facilitates; the selection of single mature sperm for ICSI [3]. The HA-binding step, similar to zona pellucida binding, eliminates dysmature sperm that exhibit cytoplasmic retention, persistent histones, and DNA chain breaks. Further, the frequencies of sperm with chromosomal disomy and diploidy are reduced by 4–6-fold in HA-bound sperm vs. semen sperm fractions [3]. This reduction is similar to the increase of chromosomal aberrations in ICSI children. Combined studies of sperm shape and chromosome probes demonstrated that sperm shape does not reliably aid selection of haploid sperm [34]. Thus, HA-mediated sperm selection is a novel and efficient technique that may alleviate potential future public health problems that are related to ICSI with visually selected sperm, such as chromosomal aneuploidies, shortened lifetime, and increased cancer rates.

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Acknowledgments

This research was supported by the NIH (HD-19505, HD-32902, OH-04061). The HA-related diagnostic and sperm selection devices were invented by Gabor Huszar, MD; the invention was assigned to Yale University who owns the patent. Yale University has licensed the invention to Biocoat Inc. Gabor Huszar is acting as a scientific advisor.

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Correspondence to Gabor Huszar MD .

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Huszar, G. (2012). Sperm Testing and ICSI Selection by Hyaluronic Acid Binding: The Hyaluronic Acid-Coated Glass Slide and Petri Dish in the Andrology and IVF Laboratories. In: Nagy, Z., Varghese, A., Agarwal, A. (eds) Practical Manual of In Vitro Fertilization. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1780-5_27

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