Mehmet Uzumcu

Associate Professor Rutgers, The State University of New Jersey Department of Animal Sciences Office 119, Laboratory 108 - Bartlett Hall Tel: 732-932-6912 Fax: 732-932-6996 uzumcu@aesop.rutgers.edu

Research

The long-term research goal in the Uzumcu laboratory is to understand the biology of the ovary and testis and the effects of the environment on the ovary and female fertility. The specific research projects are:

1. Effects of environmental endocrine disruptors exposure on ovary development and female fertility. Our research focuses on (i) the effects of developmental exposure to endocrine disruptors on adult ovarian function and female fertility, (ii) molecular mechanisms of these effects, and (iii) whether these effects are transmitted to the next generation via the female germ cells, through epigenetic mechanisms. We primarily work with the organochlorine pesticide methoxychlor (MXC). Methoxychlor is a weak estrogen, but its major metabolite HPTE and mono-OH MXC are stronger estrogen receptor (ER) agonists. In addition, HPTE and mono-OH MXC act as antagonist for ER ß and androgen receptor (AR). Most of endocrine disruptors that are widespread in the environment act as estrogenic, anti-estrogenic or anti-androgenic manner. Therefore, MXC, HPTE and mono-OH MXC represent model endocrine disruptors.
   
2. Role of local growth factors in the development of the testis. Our research focus is to understand the role of growth factors (e.g., hepatocyte growth factors; HGF) in testis differentiation, development, and function. The master switch for mammalian testis differentiation is sex-determining region of Y chromosome (SRY). The SRY carries out its function most likely through local growth factors. Hepatocyte growth factor along with its receptor, c-met, is one of the growth factors that are expressed in testis in a spatially and temporally regulated manner, suggesting that it plays an important role in the testis development.

We utilize in vivo (e.g. rats and mice) and in vitro models (e.g., cell and organ culture) as well as physiological, cellular, and molecular approaches to improve our understanding in development and function of mammalian gonad and the roles of local growth factors as well as the environment on the gonad.

Experience

Education

Professional Societies

Endocrine Society
Society for the Study of Reproduction
.

Editorial Positions

Editorial Board, Journal of Endocrinology, 2004-present
Editorial Board, Toxicology and Applied Pharmacology, 2008-present

Courses

Representative Publications

Zama AM and Uzumcu M (2009). Fetal and neonatal exposure to endocrine disruptor methoxychlor causes epigenetic alterations in key ovarian genes. Endocrinology, Jul 9. [Epub ahead of print].

Harvey CH, Esmail MY, Wang, Q, Brooks, AI, Zachow R, Uzumcu M (2009). Effect of methoxychlor metabolite HPTE on rat ovarian granulosa cell transcriptome in vitro. Toxicological Sciences 110:95-106. Epub 2009 May 4

Armenti AE, Zama AM, Passantino L, Uzumcu M (2008). Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats. Toxicology and Applied Pharmacology 233:286-296. Epub 2008 Sep 24.

Marano J, Sun D, Zama AM, Young W, Uzumcu M (2008). Orthotopic transplantation of neonatal GFP rat ovary as experimental model for studying ovarian development and toxicology. Reproductive Toxicology 26:191-196. Epub 2008 Sep 19 (Journal Cover).

Memon MA, Anway MD, Covert TR, Uzumcu M, Skinner MK (2008). Transforming growth factor beta (TGFb1, TGFb2 or TGFb3) null-mutant phenotypes in embryonic gonadal development. (Molecular and Cellular Endocrinology; Aug 26, 2008. [Epub ahead of print]).

Zachow RJ, Uzumcu M (2007). The hepatocyte growth factor system as a regulator of female and male gonadal function. Journal of Endocrinology 195:359-371.

Clement TM, Anway MD, Uzumcu M, MK Skinner (2007) Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: candidate regulatory genes. Reproduction, 134:455-472.

Uzumcu M, Zachow RJ (2007) Developmental Exposure to environmental endocrine disruptors: Consequences within the ovary and on female reproductive function. Reproductive Toxicology, 23:337-352.

Uzumcu M, Kuhn PE, Marano JE, Armenti AE, Passantino L (2006) Neonatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone (AMH) production in the rat ovary. Journal of Endocrinology, 191:549-558.

Uzumcu M, Pan Z, Chu Y, Kuhn PE, Zachow R (2006) Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro. Reproduction.132:291-299.

Anway MD, Memon MA, Uzumcu M, Skinner MK (2006) Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis. Journal of Andrology, 27:868-879

Zachow R, Uzumcu M (2006) The methoxychlor metabolite, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits steroidogenesis in rat ovarian granulosa cells in vitro. Reproductive Toxicology, 22:659-665.

Small CL, Shima JE, Uzumcu M, Skinner MK, Griswold MD (2005) Profiling gene expression during the differentiation and development of the murine embryonic gonad. Biology of Reproduction, 72:492-501.

Anway MD, Cupp AS Uzumcu M & Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science, 308:1466-1469.

Uzumcu M, Suzuki H, Skinner MK (2004) Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function. Reproductive Toxicology, 18:765-774.

Cupp AS, Uzumcu M, Suzuki H, Dirks, KA, Phillips, B, Skinner MK (2003) Effect of transient in utero exposure to the endocrine disrupter methoxychlor on embryonic and postnatal testis development. Journal of Andrology, 24:736-745.

Uzumcu M, Dirks AK, Skinner MK (2002) Inhibition of platelet-derived growth factor actions in the embryonic testis influences normal cord development and morphology. Biology of Reproduction, 66:745-753.

Uzumcu M, Westfall S, Dirks, KA, Skinner MK (2002) Embryonic testis cord formation and mesonephric cell migration requires the phosphotidylinositol 3-kinase signaling pathway. Biology of Reproduction, 67:1927-1935.

Uzumcu M, Al Homsi MF, Ball DK, Coskun S, Jaroudi K, Hollanders JMG and Brigstock DR (2000) Immunohistochemical localization of connective tissue growth factor in human endometrium and decidua Molecular Human Reproduction, 6:1093-1098.

Uzumcu M, Braileanu GT, Carnahan KG, Ludwig TE, Mirando MA (1998) Oxytocin-stimulated phosphoinositide hydrolysis and prostaglandin F2a secretion by luminal epithelial, glandular epithelial and stromal cells from pig endometrium. I. Response of cyclic pigs from day 16 post-estrus. Biology of Reproduction, 59: 1259-1265.

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