Abstract
Zucker (fa/fa) obese rats often have non-identical and differently sized paired testes, leaving one testis underdeveloped. Our earlier study found that the underdeveloped testes, > 30% smaller than the normal ones, have a selective decrease in docosapentaenoic acid (22:5n-6), a dominant fatty acid in the testes. This study was conducted to examine global testicular transcriptome profile in underdeveloped testes relative to developed ones using Rat Gene 2.0 ST Array (Affymetrix, USA). Testes were obtained from 14-week-old, sexually mature male obese (fa/fa) Zucker rats. Out of the 1790 transcripts differentially expressed, 1108 and 682 were over-expressed in the underdeveloped and normal testis, respectively (fold change ≥ 2 and P < 0.05). The ingenuity pathway analysis indicated that transcripts that were under-expressed in the underdeveloped testis, relative to the normal testes, are involved in triacylglycerol biosynthesis, sphingomyelin metabolism and phosphatidylglycerol biosynthesis. Transcripts that were over-expressed in underdeveloped testes, relative to normal testis, are involved in the production of nitric oxide and reactive oxygen species, and nuclear factor (erythroid-derived 2)-like 2 mediated oxidative stress responses. These data indicate that genes involved in lipid metabolism and oxidative stress play a crucial role in testicular growth and the maintenance of testical health.
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Abbreviations
- AA:
-
Arachidonic acid
- AGPAT1-3:
-
Acylglycerol-3-phosphate O-acyltransferase 1-3
- AKT1V:
-
akt murine thymoma viral oncogene homolog 1
- A2M:
-
Alpha-2-macroglobulin
- APOE:
-
Apolipoprotein E
- CDH2:
-
Cadherin 2, type 1, N-cadherin (neuronal)
- CGT:
-
Ceramide galactosyltransferase
- C7:
-
Complement component 7
- C1S:
-
Complement component 1, s subcomponent
- CDH2:
-
N-cadherin (neuronal)
- CST:
-
Cerebroside sulfotransferase
- DHA:
-
Docosahexaenoic acid
- DGAT2:
-
Diacylglycerol acyltransferase
- DPA:
-
Docosapentaenoic acid
- FABP:
-
Fatty acid bining protein
- ELOVL-2:
-
Elongation of very long chain fatty acids protein 2
- FADS-2:
-
Fatty acid desaturase 2
- GSN:
-
Gelsolin
- IL33:
-
Interleukin 33
- IPA:
-
Ingenuity pathway analysis
- LPCAT4:
-
Lysophosphatidylcholine acyltransferase 4
- NCBI:
-
National Centre for Biotechnology Information
- NFKB:
-
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
- NRF2:
-
Nuclear factor (erythroid-derived 2)-like 2
- OMP:
-
Olfactory marker protein
- OSMR:
-
Oncostatin M receptor
- PLIN2:
-
Perilipin
- PLPLA2:
-
Patatin-like phospholipase domain containing 2
- PUFA:
-
Polyunsaturated fatty acids
- RBL2:
-
Retinoblastoma-like 2
- RNA:
-
Ribonucleic acid
- ROS:
-
Reactive oxygen species
- RXR:
-
Retinoid X receptor
- SGMS1:
-
Sphingomyelin synthase 1
- SMPD2:
-
Sphingomyelin phosphodiesterase 2
- SORD:
-
Sorbitol degradation
- TAF7L:
-
TAF7-like RNA polymerase II
- TBX2:
-
T-box 2
- TNF:
-
Tumor necrosis factor
- TNFRSF1A:
-
Tumor necrosis factor receptor superfamily, member 1A
References
Resolve, National Infertility Association (2015) Male factor. http://www.resolve.org/about-infertility/medical-conditions/male-factor.html. Accessed 20 Oct 2015
Rolland MM, Le Moal J, Wagner V, Royère D, De Mouzon J (2013) Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and 2005 in France. Hum Reprod 28:462–470
Jensen TK, Andersson AM, Jorgensen N, Andersen AG, Carlsen E, Petersen JH, Skakkebaek NE (2004) Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 82:863–870
Sallmen M, Sandler DP, Hoppin JA, Blair A, Baird DD (2006) Reduced fertility among overweight and obese men. Epidemiology 17:520–523
Vendramini V, Cedenho AP, Miraglia SM, Spaine DM (2014) Reproductive function of the male obese Zucker rats: alteration in sperm production and sperm DNA damage. Reprod Sci 21:221–229
Suh M, Merrells KJ, Dick A, Taylor CG (2011) Testes of obese rats are highly responsive to n-3 long-chain fatty acids. Br J Nutr 106:1005–1012
Zadravec D, Tvrdik P, Guillou H, Haslam R, Kobayashi T, Napier JA et al (2011) ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice. J Lipid Res 52:245–255
Chen M, Wang X, Wang Y, Zhang L, Xu B, Lv L, Cui C, Li W, Gao F (2014) Wt1 is involved in Leydig cell steroid hormone biosynthesis by regulating paracrine factor expression in mice. Biol Reprod 90:71
Vallés AS, Aveldaño MI, Furland NE (2014) Altered lipid homeostasis in Sertoli cells stressed by mild hyperthermia. PLoS One 9:e91127
Fujimoto H, Tadano-Aritomi K, Tokumasu A, Ito K, Hikita T, Suzuki K, Ishizuka I (2000) Requirement of seminolipid in spermatogenesis revealed by UDP-galactose: ceramide galactosyltransferase-deficient mice. J Biol Chem 275:22623–22626
Hong L (2015) The effects of plant versus marine sources of dietary omega-3 fatty acids on hepatic steatosis and adipose function in fa/fa Zucker rats. http://mspace.lib.umanitoba.ca/handle/1993/30325. Accessed 20 Oct 2015
Robb GW, Amann RP, Killian GJ (1978) Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J Reprod Fertil 54:103–107
Blazejczyk M, Miron M, Nadon R (2007) FlexArray: a statistical data analysis software for gene expression microarrays. Genome Quebec, Montreal
Regassa A, Kim WK (2015) Transcriptome analysis of hen preadipocytes treated with an adipogenic cocktail (DMIOA) with or without 20(S)-hydroxylcholesterol. BMC Genomics 16:91
Lervik S, Kristoffersen AB, Conley LN, Oskam IC, Hedegaard J, Ropstad E, Olsaker I (2015) Gene expression during testis development in Duroc boars. Animal 9:1832–1842
Petit FG, Kervarrec C, Jamin SP, Smagulova F, Hao C, Becker E, Jegou B, Chalmel F, Priming M (2015) Combining RNA and protein profiling data with network interactions identifies genes associated with spermatogenesis in mouse and human. Biol Reprod 92:71
Bruggmann R, Jagannathan V, Braunschweig M (2013) In search of epigenetic marks in testes and sperm cells of differentially fed boars. PLoS One 8:e78691
Kang N, Kim H, Jae Y, Lee N, Ku CR, Margolis F, Lee EJ, Bahk YY, Kim MS, Koo J (2015) Olfactory marker protein expression is an indicator of olfactory receptor-associated events in non-olfactory tissues. PLoS One 10:e0116097
Spehr M, Gisselmann G, Poplawski A, Riffell JA, Wetzel CH, Zimmer RK, Hatt H (2003) Identification of a testicular odorant receptor mediating human sperm chemotaxis. Science 299:2054–2058
Fukuda N, Touhara K (2006) Developmental expression patterns of testicular olfactory receptor genes during mouse spermatogenesis. Genes Cells 11:71–81
Furland NE, Zanetti SR, Oresti GM, Maldonado EN, Aveldaño MI (2007) Ceramides and sphingomyelins with high proportions of very long-chain polyunsaturated fatty acids in mammalian germ cells. J Biol Chem 282:18141–18150
Kihara A (2012) Very long-chain fatty acids: elongation, physiology and related disorders. J Biochem 152:387–395
Oresti GM, Garcia-Lopez J, Aveldano MI, Del Mazo J (2013) Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2. Reproduction 146:471–480
O’Shea T, Wales RG (1965) Metabolism of sorbitol and fructose by ram spermatozoa. J Reprod Fertil 10:353–368
Jones AR, Connor DE (2000) Fructose metabolism by mature boar spermatozoa. Reprod Fertil Dev 12:355–359
Mann T, White IG (1956) Metabolism of glycerol, sorbitol and related compounds by spermatozoa. Nature 178:142–143
Medrano A, Fernandez-Novell JM, Ramio L, Alvarez J, Goldberg E, Rivera MM, Guinovart JJ, Rigau T, Rodriguez-Gil JE (2006) Utilization of citrate and lactate through a lactate dehydrogenase and ATP-regulated pathway in boar spermatozoa. Mol Reprod Dev 73:369–378
Jones AR (1997) Metabolism of lactate by mature boar spermatozoa. Reprod Fertil Dev 9:227–232
Jones AR, Chantrill LA, Cokinakis A (1992) Metabolism of glycerol by mature boar spermatozoa. J Reprod Fertil 94:129–134
Burg MB (1995) Molecular basis of osmotic regulation. Am J Physiol 268:F983–F996
Hoshi A, Takahashi M, Fujii J, Myint T, Kaneto H, Suzuki K, Yamasake Y, Kamama T, Taniguchi N (1996) Glycation and inactivation of sorbitol dehydrogenase in normal and diabetic rats. Biochem J 318:119–123
Barr FA, Sillje HH, Nigg EA (2004) Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5:429–440
van Vugt MA, Medema RH (2005) Getting in and out of mitosis with polo-like kinase-1. Oncogene 24:2844–2859
Saeednia S, Bahadoran H, Amidi F, Asadi MH, Naji M, Fallahi P, Nejad NA (2015) Nerve growth factor in human semen: effect of nerve growth factor on the normozoospermic men during cryopreservation process. Iran J Basic Med Sci 18:292–299
Li C, Zheng L, Wang C, Zhou X (2010) Absence of nerve growth factor and comparison of tyrosine kinase receptor A levels in mature spermatozoa from oligoasthenozoospermic, asthenozoospermic and fertile men. Clin Chim Acta 411:1482–1486
Nakamura BN, Lawson G, Chanc JY, Banuelos J, Cortés MM, Hoang YD, Ortiz L, Rau BA, Luderer U (2010) Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner. Free Radic Biol Med 49:1368–1379
Chen K, Mai Z, Zhou Y, Gao X, Yu B (2012) Low NRF2 mRNA expression in spermatozoa from men with low sperm motility. Tohoku J Exp Med 228:259–266
Dandona P, Aljada A, Chaudhuri A, Mohanty P, Rajesh G (2004) A novel view of metabolic syndrome. Metab Syndr Relat Disord 2:2–8
Agarwal A, Makker K, Sharma R (2008) Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol 59:2–11
Vernet N, Dennefeld C, Klopfenstein M, Ruiz A, Bok D, Ghyselinck NB et al (2008) Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation. Reproduction 136:619–626
Kastner P, Mark M, Leid M, Gansmuller A, Chin W, Grondona JM, Decimo D, Krezel W, Dierich A, Chambon P (1996) Abnormal spermatogenesis in RXR beta mutant mice. Genes Dev 10:80–92
Rode K, Sieme H, Richterich P, Brehm R (2015) Characterization of the equine blood-testis barrier during tubular development in normal and cryptorchid stallions. Theriogenol 84:763–772
Guttman JA, Janmey P, Vogl AW (2002) Gelsolin-evidence for a role in turnover of junction-related actin filaments in Sertoli cells. J Cell Sci 115:499–505
Han X, Zhang JJ, Yao N, Wang G, Mei J, Li B, Chao L, Wang ZA (2015) Polymorphisms in NFKB1 and NFKBIA genes modulate the risk of developing prostate cancer among Han Chinese. Med Sci Monit 21:1707–1715
Yang X, Li P, Tao J, Qin C, Cao Q, Gu J et al (2014) Association between NFKB1 -94ins/del ATTG promoter polymorphism and cancer susceptibility: an updated meta-analysis. Int J Genomics 2014:612972
Acknowledgements
The authors would like to thank Ms. Lena Hong for letting us use samples for the study, and Sally Li and June Lee for assisting tissue collection. This study was supported by the University of Manitoba Research Grant Program and Natural Sciences and Engineering Research Council (NSERC) of the Canada Discovery Bridge Funding Program.
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JD and AR equally ran the microarray, analysed the data and prepared the manuscript. AR is the co-first author. WKK was a co-investigator, by providing financial support for the microarray experiment. CGT and PZ designed the animal study. MS was the principal investigator, provided financial support and directed the overall studies. All authors read, edited and approved the final manuscript.
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11745_2017_4298_MOESM1_ESM.xlsx
Supplementary material 1 (XLSX 121 kb) Supplemental file 1: List of genes over-expressed in underdeveloped testes relative to normal testes
11745_2017_4298_MOESM2_ESM.xlsx
Supplementary material 2 (XLSX 80 kb) Supplemental file 2: List of genes under-expressed in underdeveloped testes relative to normal testes
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Datar, J., Regassa, A., Kim, WK. et al. Lipid Metabolism is Closely Associated with Normal Testicular Growth Based on Global Transcriptome Profiles in Normal and Underdeveloped Testis of Obese Zucker (fa/fa) Rats. Lipids 52, 951–960 (2017). https://doi.org/10.1007/s11745-017-4298-2
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DOI: https://doi.org/10.1007/s11745-017-4298-2