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Gene expression during testis development in Duroc boars

Published online by Cambridge University Press:  28 May 2015

S. Lervik ,
A. B. Kristoffersen ,
L. N. Conley ,
I. C. Oskam ,
J. Hedegaard ,
E. Ropstad  and
I. Olsaker
S. Lervik
Affiliation:
Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), Ullevålsveien 72, Pb 8146 Dep, N-0033 Oslo, Norway
A. B. Kristoffersen
Affiliation:
National Veterinary Institute, Section for Epidemiology, Ullevålsveien 68, Pb 750 Sentrum, N-0106 Oslo, Norway
L. N. Conley
Affiliation:
Faculty of Agricultural Sciences, University of Aarhus, Blichers Alle 20, Pb 50, DK-8830 Tjele, Denmark
I. C. Oskam
Affiliation:
Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), Ullevålsveien 72, Pb 8146 Dep, N-0033 Oslo, Norway
J. Hedegaard
Affiliation:
Faculty of Agricultural Sciences, University of Aarhus, Blichers Alle 20, Pb 50, DK-8830 Tjele, Denmark
E. Ropstad
Affiliation:
Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), Ullevålsveien 72, Pb 8146 Dep, N-0033 Oslo, Norway
I. Olsaker*
Affiliation:
NMBU, Faculty of Veterinary Medicine and Biosciences, Department of Basic Sciences and Aquatic Medicine, Ullevålsveien 72, Pb 8146 Dep, N-0033 Oslo, Norway
*
†E-mail: ingrid.olsaker@nmbu.no
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Abstract

Androstenone is a steroid pheromone occurring in the pubertal Leydig cells. Breeding against androstenone can decrease pheromone odour in swine meat but appears to cause unwanted side effects such as delayed onset of puberty. To study causality, global gene expression in developing boar testes at 12, 16, 20 and 27 weeks was investigated using a porcine cDNA microarray. The morphological status and androgenic levels of the same individuals have been described in a previous publication. In the present paper, expression of genes and pathways has been analysed with reference to these findings. Nine clusters of genes with significant differential expression over time and 49 functional charts were found in the analysed testis samples. Prominent pathways in the prepubertal testis were associated with tissue renewal, cell respiration and increased endocytocis. E-cadherines may be associated with the onset of pubertal development. With elevated steroidogenesis (weeks 16 to 27), there was an increase in the expression of genes in the MAPK pathway, STAR and its analogue STARD6. A pubertal shift in genes coding for cellular cholesterol transport was observed. Increased expression of meiotic pathways coincided with the morphological onset of puberty. Puberty-related change in Ca(2+) pathway transcripts, neurosteroids, neuronal changes and signalling in redox pathways suggested a developmental-specific period of neuromorphogenesis. Several growth factors were found to increase differentially over time as the testis matured. There may be interactions between MAPK, STAR and growth factors during specific periods. In conclusion, pathways for neurogenesis, morphological pathways and several transcripts for growth factors, which have known modulating effects on steroidogenesis and gonadotropins in humans and rodents, act at specific ages and developmental stages in the boar testis. The age dependency and complexity shown for development-specific testis transcripts must be considered when selecting phenotypic parameters for genetic selection for low androstenone. The results of selection based on measurement of phenotypic maturation and androstenone (or other steroid) levels at one specific age may differ depending on the age used. More research is necessary to find the optimal phenotype to use in order to reduce the unwanted side effects.

Keywords

boar testistestis developmentpubertalgene expressionpathway analysis
Type
Research Article
Information
animal , Volume 9 , Supplement 11 , November 2015 , pp. 1832 - 1842
Copyright
© The Animal Consortium 2015 

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References

Abdou, HS, Villeneuve, G and Tremblay, JJ 2013. The calcium signaling pathway regulates Leydig cell steroidogenesis through a transcriptional cascade involving the nuclear receptor NR4A1 and the steroidogenic acute regulatory protein. Endocrinology 154, 511–520.Google Scholar
Attia, RG, Dooley, CA, Rainey, WE and Carr, RB 2000. Transforming growth factor ß inhibits steroidogenic acute regulatory (StAR) protein expression in human ovarian thecal cells. Molecular and Cellular Endocrinology 170, 123–129.Google Scholar
Avelar, GF, Oliveira, CF, Soares, JM, Silva, IJ, Dobrinski, I, Hess, RA and Franca, LR 2010. Postnatal somatic cell proliferation and seminiferous tubule maturation in pigs: a non-random event. Theriogenology 74, 11–23.Google Scholar
Benjamini, Y and Hochberg, Y 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B 57, 289–300.Google Scholar
de Melker, AA, van der Horst, G and Borst, J 2004. c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15. Journal of Cell Science 117, 5001–5012.Google Scholar
Dragovic, RA, Ritter, LJ, Schulz, SJ, Amato, F, Thompson, JG, Armstrong, DT and Gilchrist, RB 2007. Oocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of mouse cumulus cell expansion. Biology of Reproduction 76, 848–857.CrossRefGoogle ScholarPubMed
Edgar, R, Domrachev, M and Lash, AE 2002. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Research 30, 207–210.Google Scholar
Eisen, MB, Spellman, PT, Brown, PO and Botstein, D 1998. Cluster analysis and display of genome-wide expression patterns. Proceedings of the National Academy of Sciences of the United States of America 95, 14863–14868.Google Scholar
Evaul, K and Hammes, SR 2008. Cross-talk between G protein-coupled and epidermal growth factor receptors regulates gonadotropin-mediated steroidogenesis in Leydig cells. Journal of Biological Chemistry 283, 27525–27533.Google Scholar
Franca, LR, Silva, VA Jr, Chiarini-Garcia, H, Garcia, SK and Debeljuk, L 2000. Cell proliferation and hormonal changes during postnatal development of the testis in the pig. Biology of Reproduction 63, 1629–1636.Google Scholar
Franca, LR, Avelar, GF and Almeida, FF 2005. Spermatogenesis and sperm transit through the epididymis in mammals with emphasis on pigs. Theriogenology 63, 300–318.Google Scholar
Gentleman, RC, Carey, VJ, Bates, DM, Bolstad, B, Dettling, M, Dudoit, S, Ellis, B, Gautier, L, Ge, Y, Gentry, J, Hornik, K, Hothorn, T, Huber, W, Iacus, S, Irizarry, R, Leisch, F, Li, C, Maechler, M, Rossini, AJ, Sawitzki, G, Smith, C, Smyth, G, Tierney, L, Yang, JY and Zhang, J 2004. Bioconductor: open software development for computational biology and bioinformatics. Genome Biology 5, R80.CrossRefGoogle ScholarPubMed
Gerendai, I, Banczerowski, P and Halasz, B 2005. Functional significance of the innervation of the gonads. Endocrine 28, 309–318.CrossRefGoogle ScholarPubMed
Gnessi, L, Basciani, S, Mariani, S, Arizzi, M, Spera, G, Wang, C, Bondjers, C, Karlsson, L and Betsholtz, C 2000. Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice. The Journal of Cell Biology 149, 1019–1026.Google Scholar
Huang, DW, Sherman, BT and Lempicki, RA 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4, 44–57.CrossRefGoogle ScholarPubMed
Jacobsen, L, Madsen, P, Moestrup, SK, Lund, AH, Tommerup, N, Nykjaer, A, Sottrup-Jensen, L, Gliemann, J and Petersen, CM 1996. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein. Journal of Biological Chemistry 271, 31379–31383.Google Scholar
Kagias, K, Nehammer, C and Pocock, R 2012. Neuronal responses to physiological stress. Frontiers in Genetics 3, 222.Google Scholar
Kanbara, K, Mori, Y, Kubota, T, Watanabe, M, Yanagawa, Y and Otsuki, Y 2011. Expression of the GABAA receptor/chloride channel in murine spermatogenic cells. Histology and Histopathology 26, 95–106.Google ScholarPubMed
Keber, R, Rozman, D and Horvat, S 2013. Sterols in spermatogenesis and sperm maturation. The Journal of Lipid Research 54, 20–33.CrossRefGoogle ScholarPubMed
Kirkup, KM, Mallin, AM and Bagnell, CA 2000. Inhibition of pig granulosa cell adhesion and growth in vitro by immunoneutralization of epithelial cadherin. Reproduction 120, 275–281.Google Scholar
Lejeune, H, Habert, R and Saez, JM 1998. Origin, proliferation and differentiation of Leydig cells. Journal of Molecular Endocrinology 20, 1–25.Google Scholar
Lervik, S, Oskam, I, Krogenaes, A, Andresen, O, Dahl, E, Haga, HA, Tajet, H, Olsaker, I and Ropstad, E 2013. Androstenone and testosterone levels and testicular morphology of Duroc boars related to estimated breeding value for androstenone. Theriogenology 79, 986–994.Google Scholar
Leung, MC, Bowley, KL and Squires, EJ 2010. Examination of testicular gene expression patterns in Yorkshire pigs with high and low levels of boar taint. Animal Biotechnology 21, 77–87.Google Scholar
Lin, T, Blaisdell, J and Haskell, JF 1987. Transforming growth factor-beta inhibits Leydig cell steroidogenesis in primary culture. Biochemical and Biophysical Research Communications 146, 387–394.CrossRefGoogle ScholarPubMed
Lin, T, Hu, J, Wang, D and Stocco, DM 1998. Interferon-gamma inhibits the steroidogenic acute regulatory protein messenger ribonucleic acid expression and protein levels in primary cultures of rat Leydig cells. Endocrinology 139, 2217–2222.Google Scholar
Manna, PR and Stocco, DM 2011. The role of specific mitogen-activated protein kinase signaling cascades in the regulation of steroidogenesis. Journal of Signal Transduction 2011, 821615.Google Scholar
Manna, PR, Chandrala, SP, Jo, Y and Stocco, DM 2006. cAMP-independent signaling regulates steroidogenesis in mouse Leydig cells in the absence of StAR phosphorylation. Journal of Molecular Endocrinology 37, 81–95.Google Scholar
Manna, PR, El-Hefnawy, T, Kero, J and Huhtaniemi, IT 2001a. Biphasic action of prolactin in the regulation of murine Leydig tumor cell functions. Endocrinology 142, 308–318.Google Scholar
Manna, PR, Kero, J, Tena-Sempere, M, Pakarinen, P, Stocco, DM and Huhtaniemi, IT 2001b. Assessment of mechanisms of thyroid hormone action in mouse Leydig cells: regulation of the steroidogenic acute regulatory protein, steroidogenesis, and luteinizing hormone receptor function. Endocrinology 142, 319–331.Google Scholar
Mendis-Handagama, SM and Siril Ariyaratne, HB 2005. Leydig cells, thyroid hormones and steroidogenesis. Indian Journal of Experimental Biology 43, 939–962.Google ScholarPubMed
Miles, DC, Wakeling, SI, Stringer, JM, van den Bergen, JA, Wilhelm, D, Sinclair, AH and Western, PS 2013. Signaling through the TGF beta-activin receptors ALK4/5/7 regulates testis formation and male germ cell development. PLoS One 8, e54606.Google Scholar
Millena, AC, Reddy, SC, Bowling, GH and Khan, SA 2004. Autocrine regulation of steroidogenic function of Leydig cells by transforming growth factor-alpha. Molecular and Cellular Endocrinology 224, 29–39.Google Scholar
Moe, M, Meuwissen, T, Lien, S, Bendixen, C, Wang, X, Conley, LN, Berget, I, Tajet, H and Grindflek, E 2007. Gene expression profiles in testis of pigs with extreme high and low levels of androstenone. BMC Genomics 8, 405–421.CrossRefGoogle ScholarPubMed
Oldknow, KJ, Seebacher, J, Goswami, T, Villen, J, Pitsillides, AA, O’Shaughnessy, PJ, Gygi, SP, Schneyer, AL and Mukherjee, A 2013. Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor beta (TGFbeta) signaling is essential for testicular aging and regulating testis size. Endocrinology 154, 1310–1320.CrossRefGoogle ScholarPubMed
Raman, M, Chen, W and Cobb, MH 2007. Differential regulation and properties of MAPKs. Oncogene 26, 3100–3112.Google Scholar
Regueira, M, Riera, MF, Galardo, MN, Pellizzari, EH, Cigorraga, SB and Meroni, SB 2014. Activation of PPAR alpha and PPAR beta/delta regulates Sertoli cell metabolism. Molecular and Cellular Endocrinology 382, 271–281.Google Scholar
Sellier, P and Bonneau, M 1988. Genetic relationships between fat androstenone level in males and development of male and female genital tract in pigs. Journal of Animal Breeding and Genetics 105, 11–20.CrossRefGoogle Scholar
Schmahl, J, Rizzolo, K and Soriano, P 2008. The PDGF signaling pathway controls multiple steroid-producing lineages. Genes & Development 22, 3255–3267.CrossRefGoogle ScholarPubMed
Smyth, GK 2004. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology 3, Article 3, 1–25.CrossRefGoogle ScholarPubMed
Tran, S, Lamba, P, Wang, Y and Bernard, DJ 2011. SMADs and FOXL2 synergistically regulate murine FSHbeta transcription via a conserved proximal promoter element. Molecular Endocrinology (Baltimore, Md.) 25, 1170–1183.CrossRefGoogle Scholar
Vasankari, T, Kujala, U, Taimela, S, Torma, A, Irjala, K and Huhtaniemi, I 1995. Effects of a long acting somatostatin analog on pituitary, adrenal, and testicular function during rest and acute exercise: unexpected stimulation of testosterone secretion. Journal of Clinical Endocrinology & Metabolism 80, 3298–3303.Google Scholar
Willems, A, Batlouni, SR, Esnal, A, Swinnen, JV, Saunders, PT, Sharpe, RM, Franca, LR, De, GK and Verhoeven, G 2010. Selective ablation of the androgen receptor in mouse Sertoli cells affects Sertoli cell maturation, barrier formation and cytoskeletal development. PLoS One 5, e14168.Google Scholar
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