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Yalcinkaya T.M.,Section of Reproductive Endocrinology | Sittadjody S.,Wake Forest Institute for Regenerative Medicine | Opara E.C.,Wake Forest Institute for Regenerative Medicine | Opara E.C.,Wake forest University
Maturitas | Year: 2014

The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system. © 2013 Elsevier Ireland Ltd.

Quaynor S.D.,Section of Reproductive Endocrinology | Quaynor S.D.,Institute of Molecular Medicine and Genetics | Quaynor S.D.,Georgia Regents University | Goldberg L.Y.,University of Kentucky | And 16 more authors.
Molecular and Cellular Endocrinology | Year: 2014

NELF, a protein identified in migratory GnRH neurons, is predominantly nuclear and alternatively spliced. However, specific NELF splice variants expressed in immortalized GnRH neuronal cell lines from mouse and human are not known. RNA from migratory (GN11 and NLT) and postmigratory (GT1-7) cells in mouse, and (FNCB4-hTERT) cells in human was subjected to RT-PCR. RT-PCR products were cloned, electrophoresed on denaturing gradient gels and sequenced. In addition, quantitative RT-PCR was performed using variant-specific primers. Western blot and immunofluorescence using confocal microscopy were performed for selected variants. Nelf variant 2 (v2), which contains a nuclear localization signal (NLS), was the predominant variant in all mouse and human GnRH neurons. Variants without a NLS (v3 in mouse; v4 in human) were identified. In mouse, v2 protein expression was nuclear, while v3 was non-nuclear. In mouse GnRH neurons, six Nelf splice variant transcripts were identified, including three previously unreported variants. In human, four NELF variant transcripts were observed. In both mouse and human, nuclear and non-nuclear variant transcript and protein were identified, explaining variable NELF cellular localization. © 2013 Elsevier Ireland Ltd.

Kim H.-G.,Section of Reproductive Endocrinology | Kim H.-G.,Max Planck Institute for Molecular Genetics | Kim H.-G.,Harvard University | Kim H.-G.,Institute of Molecular Medicine and Genetics | And 26 more authors.
American Journal of Human Genetics | Year: 2010

By defining the chromosomal breakpoint of a balanced t(10;12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty. We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q, and H690Q) in WD domains important for β propeller formation and protein-protein interaction. In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction. Our findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction. © 2010 The American Society of Human Genetics. All rights reserved.

Xu N.,Section of Reproductive Endocrinology | Xu N.,Reproductive Medicine and Developmental Neurobiology Programs in the Institute of Molecular Medicine and | Xu N.,Georgia Regents University | Bhagavath B.,Reproductive Endocrinology and Infertility | And 15 more authors.
Molecular and Cellular Endocrinology | Year: 2010

Nasal embryonic LHRH factor (NELF) has been hypothesized to participate in the migration of GnRH and olfactory neurons into the forebrain, a prerequisite for normal hypothalamic-pituitary-gonadal function in puberty and reproduction. However, the biological functions of NELF, which has no homology to any human protein, remain largely elusive. Although mRNA expression did not differ, NELF protein expression was greater in migratory than postmigratory GnRH neurons. Pituitary Nelf mRNA expression was also observed and increased 3-fold after exogenous GnRH administration. Contrary to a previous report, NELF displayed predominant nuclear localization in GnRH neurons, confirmed by mutagenesis of a putative nuclear localization signal resulting in impaired nuclear expression. NELF knockdown impaired GnRH neuronal migration of NLT cells in vitro. These findings and the identification of two putative zinc fingers suggest that NELF could be a transcription factor. Collectively, our findings implicate NELF as a nuclear protein involved in the developmental function of the reproductive axis. © 2009 Elsevier Ireland Ltd. All rights reserved.

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