Leptin Within the Subphysiological to Physiological Range Dose Dependently Improves Male Reproductive Function in an
Annett Hoffmann1, Gloria-Maria Manjowk1, Isabel Viola Wagner1
1Department of Endocrinology and Nephrology (A.H., G.-M.M., T.E., B.J., U.L., M.B., M.S., M.F., S.K.), University of Leipzig, and Integrated Research and Treatment Center (IFB) Adiposity Diseases (I.V.W., N.K., T.E., U.L., M.F., S.K.), Leipzig University Medical Center, 04103 Leipzig, Germany; and Department of Women's and Children's Health, Pediatric Endocrinology Unit (I.V.W., J.-B.S., O.S., K.S.), Karolinska Institutet and University Hospital, 17176 Stockholm, Sweden.
Abstract:
Obesity has recently been linked with reduced fertility, and the mechanisms underpinning this effect are currently unknown. The adipokine leptin is dysregulated in obesity and affects reproductive tracts; therefore, we investigated the dose-dependent effects of leptin on Leydig cell function and spermatogenesis. Eight-week-old leptin-deficient obese (ob/ob) male mice were treated with subphysiological (0.1- or 0.5-mg/kg body weight [BW]/d) or physiological (3.0-mg/kg BW/d) doses of leptin or saline for 12 weeks (chronic treatment) or 72 hours (acute treatment). We then evaluated male reproductive function markers. Mean testis weight increased significantly in the 0.1- and 3.0-mg/kg BW/d groups compared with saline controls (both P < .05). Intratesticular testosterone levels relative to testis weight significantly increased in the 0.5-mg/kg BW/d group compared with saline controls (P < .05). FSH levels increased in a dose-dependent manner with leptin treatment, whereas LH levels did not change. Leptin treatment significantly up-regulated both mRNA and protein expression of the steroidogenic enzyme cytochrome P450 17A1. Spermatogenesis improved in leptin-treated animals. Significantly more seminiferous tubules were observed in stages I-VIII (P < .01), and there were fewer abnormal seminiferous tubule structures (P < .01). Acute treatment with physiological leptin doses partially improved male reproductive markers without changing BW. Administration of subphysiological to physiological doses of leptin improves Leydig cell function and spermatogenesis.
