Defective spermatogenesis and testosterone levels in kinase suppressor of Ras1 (KSR1)-deficient mice
Elena Moretti A , Giulia Collodel A C , Giuseppe Belmonte A , Daria Noto A and Emanuele Giurisato A BA Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100 Siena, Italy.
B Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
C Corresponding author. Email: giulia.collodel@unisi.it
Reproduction, Fertility and Development 31(8) 1369-1377 https://doi.org/10.1071/RD18386
Submitted: 19 September 2018 Accepted: 8 February 2019 Published: 15 April 2019
Abstract
The aim of this study was to clarify the role of the protein kinase suppressor of Ras1 (KSR1) in spermatogenesis. Spermatogenesis in ksr1−/− mice was studied in testicular tissue and epididymal spermatozoa by light and transmission electron microscopy and by immunofluorescence using antibodies to ghrelin and 3β-hydroxysteroid dehydrogenase (3β-HSD). Blood testosterone levels were also assessed. ksr1−/− mice showed reduced epididymal sperm concentration and motility as compared with wild-type (wt) mice. Testis tissue from ksr1−/− mice revealed a prevalent spermatogenetic arrest at the spermatocyte stage; the interstitial tissue was hypertrophic and the cytoplasm of the Leydig cells was full of lipid droplets. Ghrelin signal was present in the seminiferous tubules and, particularly, in the interstitial tissue of wt mice; however, in ksr1−/− mice ghrelin expression was very weak in both the interstitial tissue and tubules. On the contrary, the signal of 3β-HSD was weak in the interstitial tissue of wt and strong in ksr1−/− mice. Testosterone levels were significantly increased in the blood of ksr1−/− mice (P < 0.05) as compared with wt. The results obtained reveal the importance of the KSR scaffold proteins in the spermatogenetic process. The study of the molecular mechanisms associated with spermatogenetic defects in a mouse model is essential to understand the factors involved in human spermatogenesis.
Additional keywords : 3β-HSD, ghrelin, immunofluorescence, Leydig cells, transmission electron microscopy.
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