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Int. J. Mol. Sci. 2016, 17(11), 1911;

SEPT12–NDC1 Complexes Are Required for Mammalian Spermiogenesis

Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan
School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
Institute of Systems Biology and Bioinformatics, National Central University, Jhongli City, Taoyuan Country 320, Taiwan
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan
Department of Chemistry, Fu Jen Catholic University, New Taipei City 242, Taiwan
Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Kaohsiung 811, Taiwan
Department of Obstetrics & Gynecology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 8 September 2016 / Revised: 4 November 2016 / Accepted: 7 November 2016 / Published: 16 November 2016
(This article belongs to the Section Biochemistry)
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Male factor infertility accounts for approximately 50 percent of infertile couples. The male factor-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile sperm, immature sperm, abnormally structured sperm, and sperm with nuclear damage. Our knockout and knock-in mice models demonstrated that SEPTIN12 (SEPT12) is vital for the formation of sperm morphological characteristics during spermiogenesis. In the clinical aspect, mutated SEPT12 in men results in oligozoospermia or teratozoospermia or both. Sperm with mutated SEPT12 revealed abnormal head and tail structures, decreased chromosomal condensation, and nuclear damage. Furthermore, several nuclear or nuclear membrane-related proteins have been identified as SEPT12 interactors through the yeast 2-hybrid system, including NDC1 transmembrane nucleoporin (NDC1). NDC1 is a major nuclear pore protein, and is critical for nuclear pore complex assembly and nuclear morphology maintenance in mammalian cells. Mutated NDC1 cause gametogenesis defects and skeletal malformations in mice, which were detected spontaneously in the A/J strain. In this study, we characterized the functional effects of SEPT12–NDC1 complexes during mammalian spermiogenesis. In mature human spermatozoa, SEPT12 and NDC1 are majorly colocalized in the centrosome regions; however, NDC1 is only slightly co-expressed with SEPT12 at the annulus of the sperm tail. In addition, SEPT12 interacts with NDC1 in the male germ cell line through coimmunoprecipitation. During murine spermiogenesis, we observed that NDC1 was located at the nuclear membrane of spermatids and at the necks of mature spermatozoa. In male germ cell lines, NDC1 overexpression restricted the localization of SEPT12 to the nucleus and repressed the filament formation of SEPT12. In mice sperm with mutated SEPT12, NDC1 dispersed around the manchette region of the sperm head and annulus, compared with concentrating at the sperm neck of wild-type sperm. These results indicate that SEPT12–NDC1 complexes are involved in mammalian spermiogenesis. View Full-Text
Keywords: male infertility; SEPT12; NDC1 male infertility; SEPT12; NDC1

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Lai, T.-H.; Wu, Y.-Y.; Wang, Y.-Y.; Chen, M.-F.; Wang, P.; Chen, T.-M.; Wu, Y.-N.; Chiang, H.-S.; Kuo, P.-L.; Lin, Y.-H. SEPT12–NDC1 Complexes Are Required for Mammalian Spermiogenesis. Int. J. Mol. Sci. 2016, 17, 1911.

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