Regulation of Stem Spermatogonia in the Mature Testis
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies, Infertility |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 1/10/2019 |
| Start Date: | April 2012 |
| End Date: | June 1, 2025 |
| Contact: | Lauren Chen, M.S. |
| Email: | luc2013@med.cornell.edu |
| Phone: | 2127465706 |
Investigative trial to evaluate the role of a glial cell lined derived neurotrophic factor
(GDNF) in regulation of spermatogonial renewal and testicular function. Goal of the trial is
to provide greater information on the mechanisms that effect stem spermatogonial maintenance
renewal and proliferation in its relation to male infertility.
(GDNF) in regulation of spermatogonial renewal and testicular function. Goal of the trial is
to provide greater information on the mechanisms that effect stem spermatogonial maintenance
renewal and proliferation in its relation to male infertility.
An essential requirement for sustaining male fertility is maintaining an adequate number of
stem spermatogonia, the foundation of spermatogenesis. To achieve this, when the stem cells
divide, some progeny must remain stem spermatogonia while other progeny differentiate. It is
obvious that the correct balance between self-renewing replication and differentiation of
stem spermatogonia is crucial to male fertility, and there is a indirect evidence that GDNF
plays an important role in maintaining this balance in the normal mature testis. However,
almost nothing is known about the in vivo regulation of this balance in the mature organ, of
the specific function of GDNF in the adult testis, or if physiological changes in GDNF
expression significantly affect the replication or differentiation of the stem cells. To
address these critical issues, a unique mouse model that allows GDNF signaling to the stem
spermatogonia to be specifically and reversibly inhibited in vivo by an ATP antagonist. With
this model, the first direct evidence that GDNF is required for maintaining the stem
spermatogonial pool in a normal mature testis. Additionally, the investigators have shown
that when inhibition of GDNF signaling is reversed, the stem cells begin to rebuild the stem
cell pool. Importantly, our data demonstrate that some stem spermatogonia are lost when GDNF
signaling is inhibited for as little as 2 days, while other stem cells survive for up to 11
days. This suggests that factors intrinsic or extrinsic to the stem cells modulate the
response to GDNF. Using this new mouse model the mechanisms responsible for the loss of stem
spermatogonia proliferation and regeneration will be investigated along with GDNF signaling
and inhibition. At the end of all of this these studies will be done on waste tissue obtained
from normal men and men with infertility who otherwise have testicular surgery for
therapeutic purposes.
stem spermatogonia, the foundation of spermatogenesis. To achieve this, when the stem cells
divide, some progeny must remain stem spermatogonia while other progeny differentiate. It is
obvious that the correct balance between self-renewing replication and differentiation of
stem spermatogonia is crucial to male fertility, and there is a indirect evidence that GDNF
plays an important role in maintaining this balance in the normal mature testis. However,
almost nothing is known about the in vivo regulation of this balance in the mature organ, of
the specific function of GDNF in the adult testis, or if physiological changes in GDNF
expression significantly affect the replication or differentiation of the stem cells. To
address these critical issues, a unique mouse model that allows GDNF signaling to the stem
spermatogonia to be specifically and reversibly inhibited in vivo by an ATP antagonist. With
this model, the first direct evidence that GDNF is required for maintaining the stem
spermatogonial pool in a normal mature testis. Additionally, the investigators have shown
that when inhibition of GDNF signaling is reversed, the stem cells begin to rebuild the stem
cell pool. Importantly, our data demonstrate that some stem spermatogonia are lost when GDNF
signaling is inhibited for as little as 2 days, while other stem cells survive for up to 11
days. This suggests that factors intrinsic or extrinsic to the stem cells modulate the
response to GDNF. Using this new mouse model the mechanisms responsible for the loss of stem
spermatogonia proliferation and regeneration will be investigated along with GDNF signaling
and inhibition. At the end of all of this these studies will be done on waste tissue obtained
from normal men and men with infertility who otherwise have testicular surgery for
therapeutic purposes.
Inclusion Criteria:
- undergoing testicular biopsy at Weill Cornell Medicine/New York Presbyterian
Exclusion Criteria:
- females and any males outside of the age parameter of 18-75 years old
We found this trial at
1
site
New York, New York 10065
Principal Investigator: Peter N. Schlegel, M.D.
Phone: 212-746-5706
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