Infertility is a prevalent condition that affects 15% of couples globally, with male factor infertility contributing to 50% of cases. Assisted reproductive technologies (ARTs), fertility treatments and changes in lifestyle are helping infertile men achieve their reproductive goals. These therapies are dependent on the infertile male producing at least a few mature sperm which is impossible in many cases of non-obstructive azoospermia (NOA). NOA is a common pathology observed in infertile males that is characterized by a lack of sperm in the ejaculate. In some cases, the etiology is known (e.g. infertility secondary to cancer treatment, genetic abnormalities) but in most cases the cause is idiopathic. Infertility secondary to medical treatment for cancer or other conditions is particularly devastating for prepubertal patients, because they are not reproductively mature and cannot safeguard their future fertility by cryopreserving sperm. Testicular biopsies containing spermatogonial stem cells (SSCs) can be obtained from these boys and cryopreserved for experimental stem cell-based therapies like SSC transplantation. Because the testicular biopsies taken from the prepubertal boys are small, isolating enough SSCs required for successful engraftment after transplantation is unlikely. In this event, a culture system that promotes the long-term expansion of human SSCs (hSSCs) in vitro may be required.
We performed high throughput, unbiased, single-cell RNA-sequencing of healthy adult human and rhesus macaque testicular tissue to identify the self-renewal and proliferation growth factors that will facilitate the development of a hSSC culture system and may facilitate the translation of SSC based therapies to the human fertility clinic. We will utilize the transcriptome data to address key question about SSC function. We anticipate that differential expression analysis will reveal genes that best distinguish different testicular cell types. We will identify cell surface markers that can be used to enrich pure populations of distinct cell types. We will analyze the gene expression profile of undifferentiated stem/progenitor spermatogonia, to identify growth factor receptors they express, as well as the corresponding ligands produced by somatic cells. Ligands whose cognate receptor exhibit exclusive expression on pSSCs will be candidates to test in pSSC culture, to assay their impact on the self-renewal and proliferation of pSSCs. Determining the precise molecular mechanisms regulating primate SSC (pSSC) behavior, may facilitate the development of a long-term hSSC culture system, that will enable the expansion and or genetic manipulation of hSSCs in vitro for the treatment of male infertility.
Education & Training
- B.A. in Biochemistry, Mount Holyoke College, MA, 2012
•Understanding the molecular mechanisms controlling spermatogonial stem cell biology
•Developing a long-term culture system for primate SSCs
•Elucidating species differences in male germ lineage development
•Developing stem cell-based therapies for the treatment of infertility
NIH/NICHD T32 fellowship on reproductive development from gonads to fetus’s.
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