Reproductive health is an issue of critical concern to millions of Americans. It is vital to the formation and continued well-being of the nation’s families in general, and to the improvement of women’s and men’s health in particular. In advances that further our understanding of reproductive processes and increase the promise of new treatment and prevention options, NICHD researchers examined the underlying mechanisms of fertility and infertility, identified early signs of a life-threatening pregnancy complication, and advanced our understanding of the causes of, and possible non-surgical treatments for, non-cancerous uterine tumors known as fibroids.

Study identifies novel puberty gene. >The mechanisms that control sexual maturation heralding the onset of adult reproductive function are one of the great mysteries of human biology. Puberty begins when a brain structure known as the hypothalamus begins secreting gonadotropin releasing hormone, the “master” reproductive hormone that regulates fertility. However, NICHD-supported researchers came a step closer to understanding the maturation process when they examined several members of a family who did not experience normal sexual maturation.

The researchers found that all of these individuals, along with another, unrelated person, had abnormalities in a gene known as GPR54. The researchers then developed an experimental mouse that did not have the gene in any form. [i]   Like their human counterparts with mutations in GPR54, the mice also did not undergo puberty. The researchers found that while GnRH was lacking in its other tissues, the mouse hypothalamus did contain normal amounts of unreleased GnRH. These findings open the door to new ways of treating the ovaries and testes that fail to mature and other conditions of human infertility associated with inadequate release of GnRH.

Changes in key protein levels may cause preeclampsia. Preeclampsia affects about 5 percent of all pregnancies and is a leading cause of maternal and fetal morbidity, disability, and death. A pregnant woman with preeclampsia has dangerously high levels of blood pressure and the condition can progress to seizures and coma (eclampsia). While the high blood pressure and the seizures can be treated, the only cure for preeclampsia is delivery. Surviving infants, often premature, are likely to require intensive neonatal care. In an important step forward, researchers found earlier and more pronounced changes in levels of several proteins in blood samples of pregnant women who developed preeclampsia, compared with those experiencing normal pregnancies. [ii]   The researchers caution that a larger trial would be needed to determine whether the protein abnormalities would enable clinicians to identify women at risk of preeclampsia and begin treatment before the condition occurs. However, their discovery may ultimately enable clinicians to prevent or cure preeclampsia by administering certain proteins to correct an underlying imbalance of factors that cause it.

Fibroid tumor studies may contribute to developing new non-surgical treatments. NICHD researchers are beginning to unravel the mystery behind the origins of fibroids, the most common benign tumors of the uterus and the leading cause of hysterectomy in the United States. [iii]   Fibroids, also known as leiomyomas, can cause severe pain and infertility and disproportionately affect African American women. In two recent studies of fibroid tumors, researchers discovered protein abnormalities that could help explain why the tumors grow and how they could be treated medically. In the study of fibroid tissues, the researchers found that the tumors consist largely of abnormally tangled, loosely-packed “threads” (fibrils) of the protein collagen. In the study of fibroid cells, the researchers found abnormally low production of dermatopontin, a protein involved in the manufacture of collagen. [iv]   The low dermatopont in level may contribute to abnormal collagen formation and ultimately to tumor development. These findings are major steps in understanding how fibroids form and may help in devising effective, non-surgical treatments for the condition.