#255 : Disrupted CD147 Causes the Acrosomal Defects of Round Spermatids and Male Infertility

Abstract

Background and Aims: CD147 is a well-known cancer cell migration and metastasis regulator. In the reproductive tract, our previous results revealed that CD147 regulates the apoptosis of spermatocytes and migration of spermatogonia and spermatocytes in the testis. However, the spermatogenesis process was inhibited at the round spermatid stage in our CD147-Stra8-Cre conditional knockout mice. We then further explored the mouse phenotypes and its underlying mechanisms. Method: CD147-Stra8-Cre conditional knockout mice (CD147-cKODDx4) were generated by cross-breeding the CD147 flox mice and DDx4-Cre male mice. Testis were collected for histological and molecular analyses. Results: The testis size and weight were significantly decreased in CD147-cKODDx4 mice compared to the control mice. There were no elongated spermatozoa in the CD147-cKODDx4 seminiferous tubules and cauda epididymis. PNA staining demonstrated the acrosomal defects on 3-5 stage of round spermatids. Consistent with morphological results, single cell-seq also demonstrated the round spermatid development loss. Mechanically, the IPO5 was identified as the interaction protein with CD147 and affected the round spermatids developments. Conclusion: The present study reveals a novel role of CD147, uncovers new mechanism underlying male infertility, and provides promising targets for the development of infertility diagnosis and treatment.