Successful islet/abdominal testis transplantation does not require Leydig cells.

Area of Science:

• Endocrinology
• Transplantation Immunology
• Reproductive Biology

Background:

• Pancreatic islet transplantation into the abdominal testis promotes long-term graft survival and function in diabetic hosts.
• The abdominal testis environment possesses unique local factors supporting islet graft success.
• Leydig cells and testosterone are abundant in the abdominal testis, prompting investigation into their role.

Purpose of the Study:

• To determine if Leydig cells and/or their secretory products are necessary for successful pancreatic islet transplantation in the abdominal testis model.
• To investigate the influence of Leydig cells and testosterone on islet graft acceptance and long-term function.

Main Methods:

• Selective elimination of Leydig cells using ethane dimethanesulfonate (EDS) in diabetic rats.
• Inhibition of Leydig cell repopulation with estradiol implants in EDS-treated recipients.
• Transplantation of pancreatic islets into the abdominal testes of treated and control diabetic rats.
• Assessment of graft survival, islet structure, vascularization, and host glycemic control.

Main Results:

• Diabetic rats receiving islet transplants into Leydig cell-depleted testes achieved and maintained normoglycemia for up to ten months.
• Transplanted islets were structurally normal, highly vascularized, and contained alpha-, beta-, and delta-cells, irrespective of Leydig cell presence.
• Beta cells demonstrated functional relationships with intraislet capillaries.

Conclusions:

• Leydig cells and their secretory products, including testosterone, are not required for protecting pancreatic islet grafts from rejection in the abdominal testis.
• These factors do not play an obligatory role in the success of the islet/abdominal testis transplantation protocol.
• Long-term beta-cell function and maintenance of normoglycemia are achievable without Leydig cells or testosterone in this model.