Abstract
Purpose
Undescended testes (UDT) are subjected to heat stress, which can disturb gonocyte transformation as well as apoptosis. This study aims to describe the apoptosis pathway occurring during minipuberty of children with unilateral (UDT), and to investigate the role of inhibin-B.
Methods
Testicular biopsies at unilateral orchidopexy of 10 boys (6–9 months old) with normal inhibin-B (n = 5) or low inhibin-B (n = 5) were selected for immunohistochemistry and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling) assay. Testicular tubules were labelled with antibodies against Anti-Müllerian hormone (AMH, Sertoli cell marker), mouse Vasa Homolog (MVH) and placental alkaline phosphatase (PLAP) (both germ cell markers), cleaved caspase3 (apoptotic marker), and followed by confocal imaging and cell counting with Fiji/ImageJ. Data were analyzed with GraphPad Prism.
Results
In males with low and normal inhibin-B, there was no statistical difference (p > 0.05) in the percentage of testicular tubules containing TUNEL + cells, number of cleaved caspase3 ± germ cells/tubule, total number of germ cells/tubule, and the percentage of fibrotic tubules or number of Sertoli cells/tubule.
Conclusions
These results suggest that inhibin-B does not regulate cell death of gonocytes and further studies are required to uncover any role of inhibin-B in gonocyte transformation.
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References
Hutson JM, Southwell BR, Li R, Lie G, Ismail K, Harisis G, Chen N (2013) The regulation of testicular descent and the effects of cryptorchidism. Endocr Rev 34(5):725–752. https://doi.org/10.1210/er.2012-1089
Hutson JM, Li R, Southwell BR, Petersen BL, Thorup J, Cortes D (2013) Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism? Front Endocrinol. https://doi.org/10.3389/fendo.2012.00176
Schneuer FJ, Milne E, Jamieson SE, Pereira G, Hansen M, Barker A, Holland AJA, Bower C, Nassar N (2018) Association between male genital anomalies and adult male reproductive disorders: a population-based data linkage study spanning more than 40 years. Lancet Child Adolesc Health 2(10):736–743. https://doi.org/10.1016/S2352-4642(18)30254-2
Manku G, Culty M (2015) Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges. Reproduction 149(3):R139–157. https://doi.org/10.1530/REP-14-0431
Hadziselimovic F (2016) Opinion: comment on evaluation and treatment of cryptorchidism: AUA/AAP and nordic consensus guidelines. Urol Int 96(3):249–254. https://doi.org/10.1159/000443741
Andersson AM, Skakkebaek NE (2001) Serum inhibin B levels during male childhood and puberty. Mol Cell Endocrinol 180(1–2):103–107
Cortes D, Clasen-Linde E, Hutson JM, Li R, Thorup J (2016) The Sertoli cell hormones inhibin-B and anti Mullerian hormone have different patterns of secretion in prepubertal cryptorchid boys. J Pediatr Surg 51(3):475–480. https://doi.org/10.1016/j.jpedsurg.2015.08.059
Li R, Thorup J, Sun C, Cortes D, Southwell B, Hutson J (2014) Immunofluorescent analysis of testicular biopsies with germ cell and sertoli cell markers shows significant MVH negative germ cell depletion with older age at orchiopexy. J Urol 191(2):458–464
Garrity MM, Burgart LJ, Riehle DL, Hill EM, Sebo TJ, Witzig T (2003) Identifying and quantifying apoptosis: navigating technical pitfalls. Mod Pathol 16(4):389–394. https://doi.org/10.1097/01.MP.0000062657.30170.92
Culty M (2009) Gonocytes, the forgotten cells of the germ cell lineage. Birth Defects Res C Embryo Today 87(1):1–26. https://doi.org/10.1002/bdrc.20142
Andersson AM, Muller J, Skakkebaek NE (1998) Different roles of prepubertal and postpubertal germ cells and Sertoli cells in the regulation of serum inhibin B levels. J Clin Endocrinol Metab 83(12):4451–4458. https://doi.org/10.1210/jcem.83.12.5360
Chojnacka K, Zarzycka M, Mruk DD (2016) Biology of the sertoli cell in the fetal, pubertal, and adult mammalian testis. Results Probl Cell Differ 58:225–251. https://doi.org/10.1007/978-3-319-31973-5_9
Cortes D, Thorup J, Hogdall E, Norgaard-Pedersen B, Petersen BL, Hogdall C (2007) The relation of germ cells per tubule in testes, serum inhibin B and FSH in cryptorchid boys. Pediatr Surg Int 23(2):163–169. https://doi.org/10.1007/s00383-006-1839-9
Meachem SJ, Nieschlag E, Simoni M (2001) Inhibin B in male reproduction: pathophysiology and clinical relevance. Eur J Endocrinol 145(5):561–571
Thorup J, Clasen-Linde E, Thorup SC, Cortes D (2015) Pre- and postoperative status of gonadotropins (FSH and LH) and inhibin-B in relation to testicular histopathology at orchiopexy in infant boys with unilateral undescended testes. J Pediatr Urol 11(1):e251. https://doi.org/10.1016/j.jpurol.2014.08.007
Cortes D, Clasen-Linde E, Hutson JM, Li R, Thorup J (2016) The Sertoli cell hormones inhibin-B and anti Müllerian hormone have different patterns of secretion in prepubertal cryptorchid boys. J Pediatr Surg 51(3):475–480. https://doi.org/10.1016/j.jpedsurg.2015.08.059
Acknowledgements
This study was supported by the Australian National Health and Medical Research Council (Grant number APP1144752) and the Victorian Government’s Operational Infrastructure Support Programme.
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Wilson, V., Thorup, J., Clasen-Linde, E. et al. Gonocyte transformation in congenital undescended testes: what is the role of inhibin-B in cell death?. Pediatr Surg Int 35, 1309–1316 (2019). https://doi.org/10.1007/s00383-019-04545-7
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DOI: https://doi.org/10.1007/s00383-019-04545-7