Biochemical markers of sperm function: male fertility and sperm selection for ICSI

Abstract

The expression of a 70 kDa chaperone protein, HspA2 (formerly called CK-M), has been identified in mature human spermatozoa. The central role of HspA2 has been established, as the expression level of this protein is related to sperm cellular maturity, DNA integrity, chromatin maturity, chromosomal aneuploidy frequency and sperm function, including fertilizing potential. The spermiogenetic events of cytoplasmic extrusion and remodelling of the plasma membrane, which facilitate the formation of zona pellucida binding site(s) in human spermatozoa, are related. Finally, the presence of the hyaluronic acid (HA) receptor on the plasma membrane of mature sperm coupled with the HA-coated slide sperm-binding assay, facilitates the testing of infertile men and the selection of single mature spermatozoa for ICSI. Because mature spermatozoa have no residual cytoplasm, the HA-bound sperm fraction is also enriched in spermatozoa that are normal by the Kruger strict morphology method.

Efficiency of hyaluronic acid (HA) sperm selection

“…It has been demonstrated that a method for invitro selection of mature spermatozoa based on sperm-HA binding results in spermatozoa for ICSI with low incidence of aneuploidies and DNA damage [1][2][3][4][5]. Since the chromosomal status and the chromatin integrity are not predictable by the observation of sperm dimension and shape [12] when performing conventional ICSI, the injection of aneuploid spermatozoa may generate chromosome aberrations in ICSI offspring [13,14]; likewise, oocyte fertilization with spermatozoa with damaged DNA may lead to an increased risk of pregnancy loss [15].…”

“…In fact, only mature spermatozoa which have extruded their specific receptors to bind to and digest HA can reach the oocyte and fertilize it. HA's role as "physiologic selector" is now well recognized also in vitro: it has been demonstrated that spermatozoa able to bind HA in vitro are those that have completed plasma membrane remodelling, cytoplasmic extrusion and nuclear maturation [1][2][3]. Furthermore, these HA-bound spermatozoa show low chromosomal aneuploidies and DNA fragmentation, and good nuclear morphology [4,5].…”

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

“…In an unpublished study from our laboratory increased number of non synonymous sequence variations were detected in p53 gene in infertile men. Expression levels of HspA2 are related to sperm maturity, DNA integrity, chromatin maturity, chromosomal aneuploidy frequency and sperm function, including fertilizing potential [57]. Reduced expression of HspA2 chaperone in the male germ cells leads to various defects during the meiotic phase and during spermiogenic maturation (delivery of DNA repair enzymes, cytoplasmic extrusion, plasma membrane remodelling), all of which may be interrupted in the absence of the HspA2 [58].…”

A prospective randomized study to evaluate the effect of hyaluronic acid sperm selection on the intracytoplasmic sperm injection outcome of patients with unexplained infertility having normal semen parameters

“…Selection of competent sperm based on its ability to bind to HA has been suggested as one of the methods to assess sperm quality. HA binding by human sperm indicates increased levels of cellular maturity, viability and un-reacted acrosomal status [2][3][4]. The proportion of Tygerberg normal morphology sperm has been found to be 3.04 fold higher in HA selected sperm [5].…”