Introduction: Leydig cells (LCs) are the primary source of testosterone (T) in men, and their dysfunction can lead to T deficiency. The growth and differentiation of LCs is influenced by the paracrine factors released by the testicular microenvironment (TME). Although it is well-known that obesity adversely affects male fertility and T production, the endogenous effects of Leptin on LSCs differentiation and the mechanism that are specific to patient’s BMI are understudied. In the present study, we focused on understanding the association of leptin induced LSC differentiation in patients with different BMI.
Methods: We obtained testicular biopsies from 15 men with testicular dysfunctions. The samples were subcategorized into obese (BMI >35), normal (BMI 25-30), and lean (BMI <25). Post isolation, culture, expansion and characterization of cells for the presence of each cell type validated (using Flow cytometry, western blot and Immunostaining), the cells were treated with different doses of Leptin ranging from 0, 1 and 10ng/ml for 24-96 hours respectively. To evaluate the effects of leptin with respect to BMI, qPCR, western blot and immune histochemistry were performed. Additionally, we subjected regular C57BL6 mice to lean, regular and obese diet to induce leanicity and obesity before exposing them to Leptin at 0, 10 and 100ug/day/IP for 7 days. Total blood, brain, testis were isolated post euthanasia. All data were presented as the means ± SEM. The statistical significance between two groups were estimated by unpaired two-tailed t test.
Results: The results of our study demonstrated that there is a strong relationship between BMI and leptin levels.Moreover, results from animal models emulated the observations made in data from human testis biopsies.
Conclusions: Our results demonstrated the influence- of leptin on LSC differentiation in respect to BMI. Further studies are necessary to identify potential therapeutic effects of leptin treatment in improving fertility in the setting of leptin resistance and obesity.
Source of Funding: Supported by the American Urological Association Research Scholar Award to H.A. J.M.H. is supported by NIH grants 1R01 HL137355, 1R01 HL107110, 1R01 HL134558, 5R01 CA136387, 5UM1 HL113460 and Soffer Family Foundation. This work was supported by National Institutes of Health Grant R01 DK130991 and Clinician Scientist Development Grant from the American Cancer Society to RR and AUA research scholar award to HA
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