Citation:

Klinefelter, G., M. Diamond, AND S. Krawetz. Immunolocalization of SP22 (Park7) on the Human Sperm Membrane is Indicative of Live Birth. Reproduction and Fertility. BioScientifica Ltd., Bristol, Uk, 6(1):RAF-24-0074, (2025). https://doi.org/10.1530/RAF-24-0074

Impact/Purpose:

This Sub-Product will provide data to support the notion that the expression of SP22 is predictive of the fertility of human sperm. Semen from fertile and infertile men will be used in this study from two donor banks in the US. The SP22 protein, a biomarker of infertility, will be used to determine if SP22 can identify differences in donors (fertile versus infertile donors). We have validated that SP22/Park7 protein is compromised on the surface of rat sperm following exposure to a wide range of toxicants.  The decrease in SP22 expression is highly correlated with a reduction in the fertility of the sperm. We hypothesize that the same will apply to human sperm, and that the expression of SP22/Park7 will be compromised on sperm from subfertile men.  By obtaining unidentified fertile and infertile sperm samples from biorepositories we hope to test this hypothesis.  Establishing that the SP22 biomarker is not only relevant to animal models but to humans leads us forward to incorporating this biomarker into epidemiology studies where we can relate human exposures to human fertility. This should shed light on whether sperm quality is declining across the globe and if so, is it related to environmental and pharmaceutical exposures.   

Description:

Abstract:   With the decline in sperm quality over recent decades, there is little doubt that the decreased efficiency of spermatogenesis in men reflects their increasing susceptibility to environmental and pharmaceutical exposures that can compromise male fecundity. More than twenty years have passed since we discovered a novel sperm membrane protein (SP22) derived from the Park7 gene that is highly correlated with the fertility of rat sperm exposed to epididymal toxicants., We subsequently discovered that SP22 originates in the testis and is also compromised during exposure to testicular toxicants. Recently, we were given an opportunity to test the hypothesis that human sperm may also have reduced fertility when levels of SP22 are significantly decreased.   Using a recombinant antibody to the functional epitope of SP22, we compared sperm from donors who achieved a live birth to donors who were not able to achieve a pregnancy.     Sperm SP22 was significantly reduced in a group of donors not able to achieve a pregnancy. A similar reduction in birth was also observed among specific Park7 and SP22 exons when a group of donors unable to achieve a pregnancy was compared to the live birth donors. To our knowledge, this is the first demonstration that SP22 expression can be compromised in men with reduced fertility.   This opens the door to incorporating SP22 analyses in future epidemiology studies, as well as developing over-the-counter testing for men with suspected male infertility. 

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