The Harvard Reproductive Endocrine Sciences Center has been dedicated to translational research in reproduction for the past 20 years. The Center uses interdisciplinary approaches to define the genetic control of puberty and reproduction in the human incorporating techniques from clinical investigation, human genetics, molecular biology, and bioinformatics. Broadly, the Center aims to continue its discovery program to find novel genes that control reproductive function and elucidate their biology to enhance the diagnostics, treatment, and counseling of patients with infertility and reproductive disorders. PROJECT 1 (Pl: Crowley) will utilize modern genetic and genomic tools to identify genes involved in the biology of GnRH neuronal development capitalizing on our unique cohort of >1,300 patients/families with isolated GnRH deficiency that has been assembled by our Phenotyping, Genotyping, &Bioinformatics Core (Core B). It will then chart the genotype-phenotype spectrum of these new genes and determine their role in both congenital GnRH deficiency and more common reproductive disorders. PROJECT 2 (Pl: Seminara) will utilize human genetics and murine studies to elucidate the interplay of the Neurokinin B and KISS1/KISS1R pathways. These studies will also draw on our unique cohort of GnRH deficient patients as well as targeted gene deletions of these systems in mice. PROJECT 3 (Pl: Kaiser) will explore the molecular biology of G-coupled protein receptors (GPCRs) and the mechanisms by which they impact human reproduction. Using mutations in both ligands and their cognate GPCRs, including those from Project 1, Project 3 will chart their biologic activity and use in vitro techniques to elucidate their cellular actions and the effects of mutations on identified reproductive pathways. CORE A: will provide organizational, logistical, and administrative support for the center investigators;CORE B: will recruit patients for genetic studies/detailed phenotyping and manage the Progeny database;CORE C: will provide web based patient centered information on reproductive disorders and will link other investigators to our Progeny database.

Public Health Relevance

This project aims to identify and study the genes which control puberty and reproduction in the human. Better understanding the genetic control of reproduction will enable us to develop better diagnostic tests, treatments, and counseling for patients with infertility and reproductive disorders.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHD1-DSR-L (32))
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De Paolo, Louis V
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Massachusetts General Hospital
United States
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Macedo, Delanie B; Abreu, Ana Paula; Reis, Ana Claudia S et al. (2014) Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3. J Clin Endocrinol Metab 99:E1097-103
Beneduzzi, Daiane; Trarbach, Ericka B; Min, Le et al. (2014) Role of gonadotropin-releasing hormone receptor mutations in patients with a wide spectrum of pubertal delay. Fertil Steril 102:838-846.e2

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