Reproduction and Infertility

Infertility is a disease that affects more than 7 million women of reproductive age and their partners in the United States. Central to reproductive health and fertility is the normal development and maturation of specialized germ line cell types known as oocytes in women, and spermatozoa (sperm) in men. Although many cases of infertility are categorized as unexplained, there are diseases that have been shown to cause loss of these critical germ line cells including women with premature ovarian failure, and men with deletions in critical genes on the Y chromosome. Additionally, exposure to radiation or chemotherapy, among other toxins, can also lead to infertility.

Broad Stem Cell Research Center faculty are primarily interested in understanding the molecular mechanisms that are responsible for building the ovarian reserve of oocytes in women, as well as the testicular spermatogonial stem cell population in men. Given that the genesis of these male and female germ line cells begins during fetal life, we use hESC and human iPSC to understand the growth and differentiation requirements responsible for creating these specialized cell types.

One of the major roadblocks to understanding the genesis of human germ line cells is identifying the appropriate pluripotent stem cell line with which to induce robust germ line cell differentiation. Faculty are currently surveying all of the hESC lines as well as the iPSC lines generated in the UCLA derivation and reprogramming laboratories for clues into the parameters that best suite germ line cell genesis. Faculty are also using specialized materials and surfaces in collaboration with faculty from the Department of Materials Science and Engineering to induce controlled differentiation towards the germ line starting from defined pluripotent colony sizes. A third project involves creating a three-dimensional environment to support the survival and maturation of these germ line cells in the laboratory.

These ongoing projects are designed to provide the foundation upon which therapeutic strategies can be built. Our hope is that our research findings will one day lead to the generation of a germ line cell type from induced pluripotent stem cells that can be used to restore fertility to individuals rendered infertile due to disease or injury.