The impact of leptin on sperm
Fayez A. Almabhouh
A and Harbindar Jeet Singh A B *
+ Author Affiliations
- Author Affiliations
A Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
B I-PerFForm, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
Reproduction, Fertility and Development 35(8) 459-468 https://doi.org/10.1071/RD22222
Published online: 18 May 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing
Abstract
Despite its important role in numerous physiological functions, including regulation of appetite and body weight, immune function and normal sexual maturation, raised leptin levels could result in significant damaging effects on sperm. The adverse effects of leptin on the male reproductive system result from its direct actions on the reproductive organs and cells instead of the hypothalamus–pituitary–gonadal axis. Binding of leptin to the receptors in the seminiferous tubular cells of the testes increases free radical production and decreases the gene expression and activity of endogenous enzymatic antioxidants. These effects are mediated via the PI3K pathway. The resultant oxidative stress causes significant damage to the seminiferous tubular cells, germ cells and sperm DNA leading to apoptosis, increased sperm DNA fragmentation, decreased sperm count, increased fraction of sperm with abnormal morphology, and decreased seminiferous tubular height and diameter. This review summarises the evidence in the literature on the adverse effects of leptin on sperm, which could underlie the often-reported sperm abnormalities in obese hyperleptinaemic infertile males. Although leptin is necessary for normal reproductive function, its raised levels could be pathologic. There is, therefore, a need to identify the cut-off level in the serum and seminal fluid above which leptin becomes pathological for better management of leptin associated adverse effects on male reproductive function.
Keywords: infertility, leptin, male fertility, oxidative stress, PI3K pathway, sperm, sperm count, sperm morphology.
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