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Volume 24, Issue 4 (July 2022) 24, 411–415; 10.4103/aja202176

Sperm hyaluronidase is critical to mammals' fertilization for its ability to disperse cumulus–oocyte complex layer

Dong-Won Seol1, Sang Hoon Joo2, Young-Hyun Kim3, Bong-Seok Song4, Bo-Woong Sim4, Sun-Uk Kim4, Soojin Park5, Gabbine Wee1, Ekyune Kim2

1 Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea
2 College of Pharmacy, Catholic University of Daegu, Gyeongbuk 38430, Korea
3 National Primate Research Center (NPCR), Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 28116, Korea
4 Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 28116, Korea
5 Department of Biochemistry and Molecular Biology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA

Correspondence: Dr. E Kim (ekyune@cu.ac.kr) or Dr. G Wee (gabbine@dgmif.re.kr)

Date of Submission 08-May-2021 Date of Acceptance 08-Sep-2021 Date of Web Publication 30-Nov-2021


Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus–oocyte complex (COC); however, their role in mammalian fertilization remains unclear. Previously, we have shown that hyaluronidase 5 (Hyal5)/Hyal7 double-knockout (dKO) mice produce significantly fewer offspring than their wild-type (WT) counterparts because of defective COC dispersal. Male infertility is mainly caused by a low sperm count. It can be further exacerbated by the deficiency of sperm hyaluronidase, which disperses the cumulus cells of the outer layer of the COC. In the current study, we evaluated the effects of a low count of Hyal-deficient sperm and conditions of ovulated oocytes on the fertilization rate using a mouse model. Our results demonstrated that a low sperm count further decreases the in vitro fertilization (IVF) rate of Hyal-deficient dKO spermatozoa. In addition, the dKO spermatozoa resulted in a fertilization rate of 12.5% upon fertilizing COCs with a thick cumulus layer, whereas the IVF rate was comparable to that of WT spermatozoa when oocytes with a thin or no cumulus layer were fertilized. Finally, we proved that the IVF rate of dKO spermatozoa could be recovered by adding rat spermatozoa as a source of sperm hyal. Our results suggest that a deficiency of proteins involved in fertilization, such as sperm hyal, has a vital role in fertilization.

Keywords: cumulus–oocyte complex; fertilization; HYAL5; HYAL7; infertility; sperm hyaluronidase

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