Journal of Clinical & Experimental Pathology
Open Access

Abstract

Male infertility affects approximately 50% of all infertile couples. The male-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile or immature sperm and sperm with structural defects such as those caused by premature chromosomal condensation and DNA damage. Our previous studies based on a knockout mice model indicated that SEPT12 proteins are critical for the terminal morphological formation of sperm. SEPT12 mutations in men result in teratozospermia and oligozospermia. In addition, the spermatozoa exhibit morphological defects of the head and tail, premature chromosomal condensation and nuclear damage. For determine the molecular functions of SEPT12, we applied a yeast 2-hybrid system to identify SEPT12 interactors. Three nuclear or nuclear membrane proteins (protamine 2, sperm-associated antigen 4 and NDC1 transmembrane nucleoproine) have been identified. NDC1 is a major nuclear pore protein and critical for nuclear pore complex assembly. In this study, we choose nucleoporin NDC1 for further analysis; in mature spermatozoa SEPT12 colocolizes with NDC1 at the neck region. During murine spermiogenesis, we found that endogenous nucleoporin NDC1 located at nuclear membrane and participated in the formation of sperm head and neck. Over-expression of NDC1 repressed the formation of SEPT12 filament structure in male germ cell lines. In animal model, mutated SEPT12D197N mice reveals the abnormal localization of NDC1 in mature sperm. In clinical aspect, NDC1 is located at broken nuclear membrane of spermatozoa from the case with SEPT12 c.474 G>A. These results provide us the spermatogenic roles of SEPT12/NDC1 complexes in mammalian spermiogenesis.

Biography

Ying-Hung Lin has completed his PhD and Postdoctoral studies from National Cheng-Kung University. He is the Associate Professor in Graduate Institute of Basic Medicine of Fu Jen University. He has published more than 28 papers in biomedicine journals and is major in molecular genetics and reproductive biology. He focuses on identification of novel genes/proteins, which are involved in mammalian spermatogenesis and further, these genes have been subjected to screen the genetic alterations and develop the molecular methods for diagnosis and classification in patients presenting with spermatogenesis defects.

Email: 084952@mail.fju.edu.tw