Klinefelter Syndrome (KS): Research Activities and Scientific Advances

Institute Activities and Advances

KS can influence many aspects of a person's entire life, starting very soon after conception. Therefore, many branches, sections, and laboratories at NICHD conduct research that is relevant to males with XXY or poly-KS variations.

Investigating Sex Chromosomes

KS arises from an unusual number of sex chromosomes, so research into these is important to finding ways to prevent or one day cure KS. Several components of the Division of Intramural Research are studying these types of problems. The Section on Epigenetics and Development is studying how X chromosome genes influence brain, reproductive, metabolic, and immune system development. The Section on Gamete Development is studying the fruit fly for insight into early gamete cell division and how an additional X chromosome can become included. Other scientists are examining the formation of male germ cells, which are present before and after fertilization and can contain an extra X. In the Section on Clinical Genomics, scientists apply information gained from biochemical and genomic studies to clinical investigations, while also studying the biomechanical mechanisms that may contribute to genetic disorders.

Understanding KS Symptoms and Preventing or Treating Them

Infertility is a key symptom in KS and many researchers at NICHD are involved in improving understanding of how sperm production fails, starting from early in development. In the Section on Clinical Genomics, scientists developed mouse models to analyze proteins that may be key in sperm production. Other research aims to explain the network of genes involved in the renewal and differentiation of spermatogonial stem cells, meiosis, and the post-meiotic differentiation of germ cells. Researchers are also exploring mechanisms behind sperm creation and the function of Leydig cells, which produce testosterone in the presence of luteinizing hormone, and searching for new gonadotropin-regulated genes involved in testicular gametogenesis, Leydig cell function, and other endocrine processes that are disrupted in KS.

Aside from infertility, scientists are working to find ways to treat other symptoms associated with KS. The Child Development and Behavior Branch (CDBB) is examining the behavioral, neurobiological, and genetic aspects of typical development and is focusing on factors that can threaten normal development. CDBB researchers are also studying prevention steps and, where intervention is needed, the most effective conditions and timing. Their findings will have implications for boys with KS, who can have some learning difficulties, such as in processing language.

Researchers in the Pediatric Growth and Nutrition Branch focus on nutritional science, childhood antecedents of adult disease, developmental endocrinology, developmental neuroendocrinology, and physical growth and body composition. Topics relevant to KS males include bone weakness and gender identity issues.

Other Activities and Advances

The projects below also study aspects of health and infertility that might be related to KS.

  • The Reproductive Medicine Network (RMN), founded in 1990, carries out large, multicenter clinical trials of diagnostic and therapeutic interventions for male and female infertility and reproductive diseases and disorders. The network is funded through the NICHD's Fertility and Infertility (FI) Branch and comprises seven research sites as well as a data coordinating center. The RMN currently has several ongoing clinical studies, including a clinical trial to determine a level of oxygen in culture media that improves live birth rates in couples undergoing in vitro fertilization.
  • The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (Formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]) is a national network of research-based centers, supported by the FI Branch, that aims to promote interactions between basic and clinical scientists with the goal of improving reproductive health.
  • The Learning Disabilities Research Centers Consortium includes four centers in Boulder, Houston, Tallahassee, and Seattle that conduct research on the causes and treatment of learning disabilities. Supported by the NICHD's CDBB, the centers emphasize, among other things, reading comprehension—how children understand what they read—which is difficult for some children with KS.
  • The Biological Testing Facility, funded under contract with the Contraceptive Discovery and Development Branch, has developed radioimmunoassay tests to accurately measure the impact of hormone treatment given orally, subcutaneously, or transdermally. In individuals with KS taking testosterone, accurate testing helps determine the appropriate dose.
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