ESPE Abstracts (2016) 86 RFC4.2

Adipocytokines Delay Pubertal Maturation of Human Sertoli Cells

Isabel V. Wagnera, Pamela Yangob, Konstantin Svechnikova, Nan D. Tranb & Olle Södera

aKarolinska Institutet, Stockholm, Sweden; bCenter of Reproductive Sciences, University of California San Francisco, San Francisco, USA

Background: Obesity and metabolic syndrome related co-morbidities are increasingly recognized in children. Reproduction is an important target of obesity complications, including adverse effects on spermatogenesis and steroidogenesis in males. Adipocytokines are key players in various complications of obesity.

Objective and hypotheses: The aim was to study the potential effects of adipocytokines on Sertoli cell function and possibly link the findings to the observed attenuation of spermatogenesis in obese males.

Method: Testicular biopsies were obtained from healthy human males (aged 25–45 years). Highly purified adult human Sertoli cells (HSCs) were isolated by fluorescence-activated cell sorting (FACS) using CD90 as a sorting marker. Cells were cultured and exposed to various concentrations of adipocytokines (10–1000 ng/ml) for 2–7 days. Gene expression in Sertoli cells was quantified by qPCR.

Results: Exposure to lower concentrations (10–100 ng/ml) of adipocytokines for 48 h did not affect the expression of Sertoli cell-specific genes. In contrast, exposure to higher doses of several adipocytokines for 48 h, in similar levels as found in obesity, increased FSH receptor (FSHR) expression. CYP26A1 expression in HSCs was downregulated after exposure to irisin, Nampt and TNFα. Long term treatment for 7 days of HSCs with higher doses of chemerin, irisin, nampt, resistin and progranulin significantly suppressed FSHR expression (by 79, 83, 64, 71 and 26%, respectively) and upregulated CYP26A1 expression (by 48, 90, 126, 126 and 153%, respectively) as found in the prepubertal state. Further, those same adipocytokines significantly attenuated the expression of BMP-4, GDNF, LIF and FGF-2 by HSCs.

Conclusion: We propose that adipocytokines at high concentrations, frequently observed in obese children, might delay maturation of Sertoli cells during puberty and keep the Sertoli cells in a quiescent state. This may negatively affect male reproductive function including spermatogenesis and steroidogenesis in adult life.

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