Aberrant Expression of Dynein light chain 1 (DYNLT1) is Associated with Human Male Factor Infertility*

Sivankutty Indu,Sreejac Sekhar,Jeeva Sengottaiyan,Anil Kumar,Sathym Pillai,Malini Laloraya,Pradeepg Kumar

doi:10.1074/mcp.m115.050005

Sivankutty Indu, Sreejac Sekhar + Show 5 more

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https://doi.org/10.1074/mcp.m115.050005

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Abstract

DYNLT1 is a member of a gene family identified within the t-complex of the mouse, which has been linked with male germ cell development and function in the mouse and the fly. Though defects in the expression of this gene are associated with male sterility in both these models, there has been no study examining its association with spermatogenic defects in human males. In this study, we evaluated the levels of DYNLT1 and its expression product in the germ cells of fertile human males and males suffering from spermatogenic defects. We screened fertile (n = 14), asthenozoospermic (n = 15), oligozoospermic (n = 20) and teratozoospermic (n = 23) males using PCR and Western blot analysis. Semiquantitative PCR indicated either undetectable or significantly lower levels of expression of DYNLT1 in the germ cells from several patients from across the three infertility syndrome groups, when compared with that of fertile controls. DYNLT1 was localized on head, mid-piece, and tail segments of spermatozoa from fertile males. Spermatozoa from infertile males presented either a total absence of DYNLT1 or its absence in the tail region. Majority of the infertile individuals showed negligible levels of localization of DYNLT1 on the spermatozoa. Overexpression of DYNLT1 in GC1-spg cell line resulted in the up-regulation of several cytoskeletal proteins and molecular chaperones involved in cell cycle regulation. Defective expression of DYNLT1 was associated with male factor infertility syndromes in our study population. Proteome level changes in GC1-spg cells overexpressing DYNLT1 were suggestive of its possible function in germ cell development. We have discussed the implications of these observations in the light of the known functions of DYNLT1, which included protein trafficking, membrane vesiculation, cell cycle regulation, and stem cell differentiation.

Highlights

From the ‡Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram 695 014, Kerala, India; §Dr SathyPillai, Samad Hospital, V.V.Road, Pattoor, Thiruvananthapuram695035
The spermatozoa from infertile males showed a complete absence of DYNLT1 from the tail region, though this protein was present on the head and mid piece of these cells in asthenozoospermic (Fig. 2, A254), oligozoospermic (Fig. 2, O19) and teratozoospermic (Fig. 2, T244) men
DYNLT1 gene family was identified as a member of the t-complex of the mouse, which has been linked with male germ cell development and function in mouse [1, 27] and the fly [28, 29]

Summary

Introduction

From the ‡Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram 695 014, Kerala, India; §Dr SathyPillai, Samad Hospital, V.V.Road, Pattoor, Thiruvananthapuram695035. Tctex-1 (t-complex testis expressed-1), lately renamed as dynein light chain 1 (Dynlt1), is identified as a candidate gene involved in male sterility in mice [1] and maps to the t-complex in mice [3]. DYNLT1 can function in dynein-independent fashion as a cell fate regulator by its interaction with G-protein ␤ ␥ subunit regulating initial neurite sprouting [18], axonal specification, and elongation of hippocampal neurons in culture [11, 19]. The expression of DYNLT1 in human testicular germ cells and its association, if any, with human male factor subfertility are not yet evaluated. This study evaluates the association between DYNLT1expression and spermatogenesis in infertile human males and the possible function of DYNLT1 in spermatogonial cell division and differentiation

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