Regulation of Stem Spermatogonia in the Mature Testis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Regulation of Stem Spermatogonia in the Mature Testis

Conditions
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Male Infertility

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue obtained from infertile patients | Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue. | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spermatogonial stem cell, Male Infertility