Adipocytokines may delay pubertal maturation of human Sertoli cells
I. V. Wagner
A B D , P. Yango C , K. Svechnikov A , N. D. Tran C and O. Söder A
+ Author Affiliations
- Author Affiliations
A Karolinska Institutet, Department of Women’s and Children’s Health, Pediatric Endocrinology Unit, 17176 Stockholm, Sweden.
B Department of Pediatrics, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
C Center for Reproductive Sciences, University of California, San Francisco, 513 Parnassus Avenue, CA 94143, USA.
D Corresponding author. Email: isabel.wagner@ki.se
Reproduction, Fertility and Development 31(8) 1395-1400 https://doi.org/10.1071/RD18487
Submitted: 5 August 2018 Accepted: 15 February 2019 Published: 6 May 2019
Abstract
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 (10–1000 ng mL−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 in vitro, 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.
Additional keywords: fertility problems, obesity, Sertoli cell function.
References
Al-Rawaf, H. A. (2018). Circulating microRNAs and adipokines as markers of metabolic syndrome in adolescents with obesity. Clin. Nutr. , .| Circulating microRNAs and adipokines as markers of metabolic syndrome in adolescents with obesity.Crossref | GoogleScholarGoogle Scholar | 30309709PubMed |
Blázquez, M., Medina, P., Crespo, B., Gómez, A., and Zanuy, S. (2017). Identification of conserved genes triggering puberty in European sea bass males (Dicentrarchus labrax) by microarray expression profiling. BMC Genomics 18, 441.
| Identification of conserved genes triggering puberty in European sea bass males (Dicentrarchus labrax) by microarray expression profiling.Crossref | GoogleScholarGoogle Scholar | 28583077PubMed |
Caminos, J. E., Nogueiras, R., Gaytán, F., Pineda, R., González, C. R., Barreiro, M. L., Castaño, J. P., Malagón, M. M., Pinilla, L., Toppari, J., Diéguez, C., and Tena-Sempere, M. (2008). Novel expression and direct effects of adiponectin in the rat testis. Endocrinology 149, 3390–3402.
| Novel expression and direct effects of adiponectin in the rat testis.Crossref | GoogleScholarGoogle Scholar | 18403483PubMed |
Davidson, L. M., Millar, K., Jones, C., Fatum, M., and Coward, K. (2015). Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility. Hum. Fertil. (Camb.) 18, 184–193.
| Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility.Crossref | GoogleScholarGoogle Scholar | 26205254PubMed |
Du Plessis, S. S., Cabler, S., McAlister, D. A., Sabanegh, E., and Agarwal, A. (2010). The effect of obesity on sperm disorders and male infertility. Nat. Rev. Urol. 7, 153–161.
| The effect of obesity on sperm disorders and male infertility.Crossref | GoogleScholarGoogle Scholar | 20157305PubMed |
Dupont, J., Pollet-Villard, X., Reverchon, M., Mellouk, N., and Levy, R. (2015). Adipokines in human reproduction. Horm. Mol. Biol. Clin. Investig. 24, 11–24.
| Adipokines in human reproduction.Crossref | GoogleScholarGoogle Scholar | 26574894PubMed |
Erdemir, F., Atilgan, D., Markoc, F., Boztepe, O., Suha-Parlaktas, B., and Sahin, S. (2012). The effect of diet induced obesity on testicular tissue and serum oxidative stress parameters. Actas Urol. Esp. 36, 153–159.
| The effect of diet induced obesity on testicular tissue and serum oxidative stress parameters.Crossref | GoogleScholarGoogle Scholar | 21959063PubMed |
Hong, C. Y., Park, J. H., Ahn, R. S., Im, S. Y., Choi, H. S., Soh, J., Mellon, S. H., and Lee, K. (2004). Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alpha. Mol. Cell. Biol. 24, 2593–2604.
| Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alpha.Crossref | GoogleScholarGoogle Scholar | 15024051PubMed |
Ikeda, Y., Hama, S., Kajimoto, K., Okuno, T., Tsuchiya, H., and Kogure, K. (2011). Quantitative comparison of adipocytokine gene expression during adipocyte maturation in non-obese and obese rats. Biol. Pharm. Bull. 34, 865–870.
| Quantitative comparison of adipocytokine gene expression during adipocyte maturation in non-obese and obese rats.Crossref | GoogleScholarGoogle Scholar | 21628885PubMed |
Ishikawa, T., Fujioka, H., Ishimura, T., Takenaka, A., and Fujisawa, M. (2007). Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia 39, 22–27.
| Expression of leptin and leptin receptor in the testis of fertile and infertile patients.Crossref | GoogleScholarGoogle Scholar | 17212806PubMed |
Kawwass, J. F., Summer, R., and Kallen, C. B. (2015). Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review. Mol. Hum. Reprod. 21, 617–632.
| Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review.Crossref | GoogleScholarGoogle Scholar | 25964237PubMed |
Li, L., Ma, P., Huang, C., Liu, Y., Zhang, Y., Gao, C., Xiao, T., Ren, P. G., Zabel, B. A., and Zhang, J. V. (2014). Expression of chemerin and its receptors in rat testes and its action on testosterone secretion. J. Endocrinol. 220, 155–163.
| Expression of chemerin and its receptors in rat testes and its action on testosterone secretion.Crossref | GoogleScholarGoogle Scholar | 24301613PubMed |
Morrison, C. (2008). Interaction between exercise and leptin in the treatment of obesity. Diabetes 57, 534–535.
| Interaction between exercise and leptin in the treatment of obesity.Crossref | GoogleScholarGoogle Scholar | 18305149PubMed |
Nogueiras, R., Barreiro, M. L., Caminos, J. E., Gaytán, F., Suominen, J. S., Navarro, V. M., Casanueva, F. F., Aguilar, E., Toppari, J., Diéguez, C., and Tena-Sempere, M. (2004). Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors. J. Cell Sci. 117, 3247–3257.
| Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors.Crossref | GoogleScholarGoogle Scholar | 15226398PubMed |
Ocón-Grove, O. M., Krzysik-Walker, S. M., Maddineni, S. R., Hendricks, G. L., and Ramachandran, R. (2008). Adiponectin and its receptors are expressed in the chicken testis: influence of sexual maturation on testicular ADIPOR1 and ADIPOR2 mRNA abundance. Reproduction 136, 627–638.
| Adiponectin and its receptors are expressed in the chicken testis: influence of sexual maturation on testicular ADIPOR1 and ADIPOR2 mRNA abundance.Crossref | GoogleScholarGoogle Scholar | 18660386PubMed |
Paasch, U., Grunewald, S., Kratzsch, J., and Glander, H. J. (2010). Obesity and age affect male fertility potential. Fertil. Steril. 94, 2898–2901.
| Obesity and age affect male fertility potential.Crossref | GoogleScholarGoogle Scholar | 20667533PubMed |
Palmer, N. O., Bakos, H. W., Fullston, T., and Lane, M. (2012). Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2, 253–263.
| Impact of obesity on male fertility, sperm function and molecular composition.Crossref | GoogleScholarGoogle Scholar | 23248766PubMed |
Pinhas-Hamiel, O., and Zeitler, P. (1996). Insulin resistance, obesity, and related disorders among black adolescents. J. Pediatr. 129, 319–321.
| Insulin resistance, obesity, and related disorders among black adolescents.Crossref | GoogleScholarGoogle Scholar | 8804318PubMed |
Reinehr, T., and Roth, C. L. (2018). Inflammation markers in type 2 diabetes and the metabolic syndrome in the pediatric population. Curr. Diab. Rep. 18, 131.
| Inflammation markers in type 2 diabetes and the metabolic syndrome in the pediatric population.Crossref | GoogleScholarGoogle Scholar | 30338401PubMed |
Robeva, R., Tomova, A., Kirilov, G., and Kumanov, P. (2012). Anti-Müllerian hormone and inhibin B levels reflect altered Sertoli cell function in men with metabolic syndrome. Andrologia 44, 329–334.
| Anti-Müllerian hormone and inhibin B levels reflect altered Sertoli cell function in men with metabolic syndrome.Crossref | GoogleScholarGoogle Scholar | 21749433PubMed |
Rodríguez-Marí, A., Cañestro, C., BreMiller, R. A., Catchen, J. M., Yan, Y. L., and Postlethwait, J. H. (2013). Retinoic acid metabolic genes, meiosis, and gonadal sex differentiation in zebrafish. PLoS One 8, e73951.
| Retinoic acid metabolic genes, meiosis, and gonadal sex differentiation in zebrafish.Crossref | GoogleScholarGoogle Scholar | 24040125PubMed |
Roumaud, P., and Martin, L. J. (2015). Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity. Horm. Mol. Biol. Clin. Investig. 24, 25–45.
| Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.Crossref | GoogleScholarGoogle Scholar | 26587746PubMed |
Sliwowska, J. H., Ziarniak, K., Dudek, M., Matuszewska, J., and Tena-Sempere, M. (2019). Dangerous liaisons for pubertal maturation: the impact of alcohol consumption and obesity on the timing of puberty. Biol. Reprod. 100, 25–40.
| Dangerous liaisons for pubertal maturation: the impact of alcohol consumption and obesity on the timing of puberty.Crossref | GoogleScholarGoogle Scholar | 30052777PubMed |
Smith, J. F., Yango, P., Altman, E., Choudhry, S., Poelzl, A., Zamah, A. M., Rosen, M., Klatsky, P. C., and Tran, N. D. (2014). Testicular niche required for human spermatogonial stem cell expansion. Stem Cells Transl. Med. 3, 1043–1054.
| Testicular niche required for human spermatogonial stem cell expansion.Crossref | GoogleScholarGoogle Scholar | 25038247PubMed |
Thomas, S., Kratzsch, D., Schaab, M., Scholz, M., Grunewald, S., Thiery, J., Paasch, U., and Kratzsch, J. (2013). Seminal plasma adipokine levels are correlated with functional characteristics of spermatozoa. Fertil. Steril. 99, 1256–1263.e3.
| Seminal plasma adipokine levels are correlated with functional characteristics of spermatozoa.Crossref | GoogleScholarGoogle Scholar | 23375204PubMed |
Trayhurn, P., and Wood, I. S. (2004). Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br. J. Nutr. 92, 347–355.
| Adipokines: inflammation and the pleiotropic role of white adipose tissue.Crossref | GoogleScholarGoogle Scholar | 15469638PubMed |
Wagner, I. V., Sabin, M. A., Pfäffle, R. W., Hiemisch, A., Sergeyev, E., Körner, A., and Kiess, W. (2012). Effects of obesity on human sexual development. Nat. Rev. Endocrinol. 8, 246–254.
| Effects of obesity on human sexual development.Crossref | GoogleScholarGoogle Scholar | 22290357PubMed |
Wagner, I. V., Klöting, N., Atanassova, N., Savchuk, I., Spröte, C., Kiess, W., Söder, O., and Svechnikov, K. (2016). Prepubertal onset of obesity negatively impacts on testicular steroidogenesis in rats. Mol. Cell. Endocrinol. 437, 154–162.
| Prepubertal onset of obesity negatively impacts on testicular steroidogenesis in rats.Crossref | GoogleScholarGoogle Scholar | 27544779PubMed |
Walker, W. H. (2010). Non-classical actions of testosterone and spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1557–1569.
| Non-classical actions of testosterone and spermatogenesis.Crossref | GoogleScholarGoogle Scholar | 20403869PubMed |
Yango, P., Altman, E., Smith, J. F., Klatsky, P. C., and Tran, N. D. (2014). Optimizing cryopreservation of human spermatogonial stem cells: comparing the effectiveness of testicular tissue and single cell suspension cryopreservation. Fertil. Steril. 102, 1491–1498.e1.
| Optimizing cryopreservation of human spermatogonial stem cells: comparing the effectiveness of testicular tissue and single cell suspension cryopreservation.Crossref | GoogleScholarGoogle Scholar | 25241367PubMed |
