期刊
REPRODUCTION FERTILITY AND DEVELOPMENT
卷 31, 期 8, 页码 1395-1400出版社
CSIRO PUBLISHING
DOI: 10.1071/RD18487
关键词
fertility problems; obesity; Sertoli cell function
资金
- European Union's Horizon 2020 research and innovation program [634880]
- Swedish Research Council
- Frimurare Barnhuset Foundation
- Kronprinsessan Lovisas Foundation
- Sallskapet Barnavard
- Stiftelsen Samariten
- European Society for Paediatric Endocrinology Research Fellowship
- IFB (Integriertes Forschungs- und Behandlungszentrum) Adiposity Diseases
Reproduction is an important target of obesity complications, including adverse effects on spermatogenesis and steroidogenesis. Adipocytokines are key mediators in various complications of obesity. Our aim was to study the potential of adipocytokines to affect Sertoli cell function, which is crucial for spermatogenesis, and possibly link these findings to the observed attenuation of spermatogenesis in obese males. Testicular biopsies were obtained from healthy donors. Highly purified adult human Sertoli cells (HSCs) were isolated by fluorescence-activated cell sorting. Cells were cultured and exposed to different concentrations of adipocytokines (10-1000ngmL(-1)) for 2-7 days. Expression of selected Sertoli cell genes was quantified by quantitative polymerase chain reaction. Long-term treatment (7 days) of HSCs with higher concentrations of chemerin, irisin, nicotinamide phosphoribosyltransferase (Nampt), resistin and progranulin significantly suppressed FSH receptor expression (by 79%, 83%, 64%, 71% and 26% respectively; P<0.005 for all) and significantly upregulated cytochrome P450 family 26 subfamily A member 1 (CYP26A1) expression (by 48%, 90%, 126%, 126% and 153% respectively P<0.005 for all), comparable to what is found in the prepubertal state. Further, these adipocytokines significantly attenuated the expression of bone morphogenetic protein-4, glial cell line-derived neurotrophic factor, leukaemia inhibitory factor and fibroblast growth factor-2 by HSCs. We propose that adipocytokines, at high concentrations, which are often observed in obese males when tested invitro, may negatively affect Sertoli cell maturation and retain these cells in a more prepubertal stage. This could negatively affect testis function and add to fertility problems in obese adults.
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