Dataset Information

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

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.

SUBMITTER: Indu S

PROVIDER: S-EPMC4762626 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Indu Sivankutty S Sekhar Sreeja C SC Sengottaiyan Jeeva J Kumar Anil A Pillai Sathy M SM Laloraya Malini M Kumar Pradeep G PG

Molecular & cellular proteomics : MCP 20151002 12

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 su ...[more]

PMID: 26432663

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Project description:Dynein transport along the cytoskeletal microtubules towards the minus end is essential for cell division, cell migration and other basic cellular functions. Dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) has been previously associated with pancreatic ductal adenocarcinoma, hepatocellular carcinoma and prostate cancer. Cytoskeletal structures are involved in the regulation of the mucosal barrier integrity. Thus, improving our understanding of the molecular mechanisms that regulate the mucosal barrier is critical for cancer management and treatment. The present study aimed to investigate DYNC1LI1 expression in colorectal cancer (CRC) tissues. The American Joint Committee on Cancer Stage II CRC cell line LS 174T was used to determine the association between the cellular expression levels of DYNC1LI1 and different types of mucin (MUC) by reverse transcription‑quantitative PCR. The role of DYNC1LI1 in cell chemosensitivity and proliferation was also evaluated in the presence of the DNA analog 5‑fluorouracil (5‑FU) or the platinum‑based drug, oxaliplatin by the MTT assay. LS 174T cells with decreased expression levels of DYNC1LI1 were discovered to be more sensitive to 5‑FU compared with LS 174T cells with endogenous DYNC1LI1 expression levels. Moreover, LS 174T cells transfected with short hairpin RNA targeting DYNC1LI1 were associated with low MUC1 and high MUC2, MUC4 and MUC5AC expression levels. Notably, the CRC cells with low MUC1 expression levels and high expression levels of the other MUCs (MUC2, MU4 and MUC5AC) were shown to benefit from 5‑FU treatment. In conclusion, the findings of the present study have suggested that DYNC1LI1 expression may be significantly associated with MUC expression levels and may be used to predict the chemotherapeutic efficiency. However, additional functional studies and clinical reports are required for an improved understanding of the significance of these molecular interactions in tumorigenesis.

Dataset Information

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

Publications

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

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