The first request for applications was issued in 1996, and the first four awards were issued in 1998. The program, supported through NICHD's Fertility and Infertility Branch (FIB) through a P50 funding mechanism, now includes nine sites around the country. In the last competition, NCTRI’s research scope expanded to inc
Origins and differentiation of germ cells; the endocrine, paracrine, and physiologic mechanisms involved in gametogenesis, including germ cell-somatic cell interactions, germ cell proliferation and apoptosis, blood-testis barrier formation, and germ cell transplantation; fertilization, including sperm motility and capacitation, zona pellucida binding, and mechanisms to block polyspermy; pre-implantation embryonic development, including zygotic gene activation, mechanisms regulating embryonic stem cell self-renewal and differentiation, and maintenance of stem cell pluripotency; use of genetically modified stem cells to treat animal models of reproductive disorders affecting fertility.
Folliculogenesis, including studies addressing intraovarian control of follicle selection and atresia by growth factors, cytokines, and their respective binding proteins and receptor antagonists; luteogenesis and luteolysis, including intraovarian mechanisms that control luteal life span; implantation, including cell-to-cell interactions and embryo-uterine communication; the role of angiogenesis in ovarian and endometrial function; correlation of segmental gene expression with structure and function of the oviduct and epididymis.
AFundamental mechanisms of hormone synthesis, secretion, regulation, and action in the context of reproduction; developmental control of gonadotropin-releasing hormone (GnRH) neuronal migration and targeting; intraneuronal mechanisms and glia-neuron interactions controlling pulsatile GnRH secretion; intrapituitary mechanisms governing gonadotropin secretion; identification of elements and factors controlling gene transcription, including ensembles of co-activators and co-repressors, and identification of signaling molecules and pathways mediating hormone action; interaction of the immune and neuroendocrine systems in controlling fertility; mechanisms by which nutritional modification alters the hypothalamo-pituitary-gonadal endocrine axis.
Genetics of sex determination, including clarification of the functional interactions between the known sex determination genes; genes, pathways, and epigenetic mechanisms that are important in reproduction, including those involved in imprinting of genes, differential expression of maternally versus paternally inherited alleles, and DNA methylation during gametogenesis and embryogenesis; elucidation of the genes, genetic, and epigenetic mechanisms responsible for normal and skewed X-chromosome inactivation and the epigenetic modification in gametogenesis that leads to transgenerational inheritance of health and disease.
Etiology, pathophysiology, prevention, and treatment of male or female infertility, with particular emphasis on defining those conditions that are either genetically based or may have a significant epigenetic component; relation of endometriosis and uterine leiomyomas to infertility, diagnosis, management, and treatment of other benign gynecologic diseases; research leading to improved outcomes across the spectrum of assisted reproductive technologies, as well as development of new approaches for assisted reproduction; use of genomics and proteomics to develop novel diagnostics for reproductive diseases and disorders particularly in adolescents; role of parental health on gamete quality and function.
The linkage between fertility status and overall fitness.
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