Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Maternal obesity in the rat impairs male offspring aging of the testicular antioxidant defence system

Claudia J. Bautista A , Guadalupe L. Rodríguez-González A , Angélica Morales A , Consuelo Lomas-Soria A , Fabiola Cruz-Pérez A , Luis A. Reyes-Castro A and Elena Zambrano A B
+ Author Affiliations
- Author Affiliations

A Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Departamento de Biología de la Reproducción, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, México, D.F. México.

B Corresponding author. Email: zamgon@yahoo.com.mx

Reproduction, Fertility and Development 29(10) 1950-1957 https://doi.org/10.1071/RD16277
Submitted: 25 November 2015  Accepted: 15 November 2016   Published: 9 January 2017

Abstract

A high-fat diet during intrauterine development predisposes offspring (F1) to phenotypic alterations, such as lipid synthesis imbalance and increased oxidative stress, causing changes in male fertility. The objective of this study was to evaluate the effects of maternal obesity during pregnancy and lactation on antioxidant enzymes in the F1 testes. Female Wistar rats (F0) were fed either a control (C, 5% fat) or an obesogenic (MO, maternal obesity, 25% fat) diet from weaning and throughout subsequent pregnancy and lactation. F1 offspring were weaned to the control diet. Testes were retrieved at 110, 450 and 650 postnatal days (PND) for real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) antioxidant enzyme analyses. Catalase was similar between groups by RT-qPCR, whereas by IHC it was higher in the MO group at all ages than in the C group. Superoxide dismutase 1 (SOD1) had lower expression at PND 110 in MO than in C by both techniques; at PND 450 and 650 by immunoanalysis SOD1 was higher in MO than in C. Glutathione peroxidase 1 (GPX1), GPX2 and GPX4 by RT-qPCR were similar between groups and ages; by IHC GPX1/2 was higher in MO than in C, whereas GPX4 showed the opposite result at PND 110 and 450. In conclusion, antioxidant enzymes in the rat testes are modified with age. Maternal obesity negatively affects the F1 testicular antioxidant defence system, which, in turn, can explain the decrease in reproductive capacity.

Additional keywords: catalase, glutathione peroxidase, reproductive programming, superoxide dismutase, testes function.


References

Agarwal, A., Sharma, R. K., Desai, N. R., Prabakaran, S., Tavares, A., and Sabanegh, E. (2009). Role of oxidative stress in pathogenesis of varicocele and infertility. Urology 73, 461–469.
Role of oxidative stress in pathogenesis of varicocele and infertility.CrossRef |

Aitken, R. J. (1995). Free radicals, lipid peroxidation and sperm function. Reprod. Fertil. Dev. 7, 659–668.
Free radicals, lipid peroxidation and sperm function.CrossRef | 1:CAS:528:DyaK28Xht1Clsrw%3D&md5=fdfc7c6c87a40c0bade5e08b63f7b638CAS |

Aitken, R. J., and Roman, S. D. (2008). Antioxidant systems and oxidative stress in the testes. Oxid. Med. Cell. Longev. 1, 15–24.
Antioxidant systems and oxidative stress in the testes.CrossRef |

Cao, L., Leers-Sucheta, S., and Azhar, S. (2004). Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells. J. Steroid Biochem. Mol. Biol. 88, 61–67.
Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells.CrossRef | 1:CAS:528:DC%2BD2cXitFCjtrw%3D&md5=1a77d0016becf029ce4a8dba37ceb656CAS |

Connor, K. L., Vickers, M. H., Beltrand, J., Meaney, M. J., and Sloboda, D. M. (2012). Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function. J. Physiol. 590, 2167–2180.
Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function.CrossRef | 1:CAS:528:DC%2BC38XnsVOgt7w%3D&md5=29e4488fa1aecb5f7273da6da5d46d55CAS |

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 | 1:CAS:528:DC%2BC2MXhvVSltrjN&md5=380c72fa4352a67df3932121b00e08c5CAS |

Desai, M., Jellyman, J. K., Han, G., Beall, M., Lane, R. H., and Ross, M. G. (2014). Maternal obesity and high-fat diet program offspring metabolic syndrome. Am. J. Obstet. Gynecol. 211, 237.e1–237.e13.
Maternal obesity and high-fat diet program offspring metabolic syndrome.CrossRef |

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 | 1:STN:280:DC%2BC38rjtlajtQ%3D%3D&md5=40326ba1060cdc3fef9414ada1003edeCAS |

Ferramosca, A., Conte, A., Moscatelli, N., and Zara, V. (2016). A high-fat diet negatively affects rat sperm mitochondrial respiration. Andrology 4, 520–525.
A high-fat diet negatively affects rat sperm mitochondrial respiration.CrossRef | 1:CAS:528:DC%2BC28Xnt1KltLw%3D&md5=b46f223fea093da4cada09424618a2b8CAS |

Fujii, J., Iuchi, Y., Matsuki, S., and Ishii, T. (2003). Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues. Asian J. Androl. 5, 231–242.
| 1:CAS:528:DC%2BD3sXptlahs7Y%3D&md5=a741214dac033814bf1ecc07e91930efCAS |

Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., and Shimomura, I. (2004). Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114, 1752–1761.
Increased oxidative stress in obesity and its impact on metabolic syndrome.CrossRef | 1:CAS:528:DC%2BD2cXhtFaiur7F&md5=29cd8d0d8ae9157dc6accb1824e30750CAS |

Gao, F., Liu, Y. C., Zhang, Z. H., Zhang, C. Z., Su, H. W., and Li, S. L. (2012). Effect of prepartum maternal energy density on the growth performance, immunity, and antioxidation capability of neonatal calves. J. Dairy Sci. 95, 4510–4518.
Effect of prepartum maternal energy density on the growth performance, immunity, and antioxidation capability of neonatal calves.CrossRef | 1:CAS:528:DC%2BC38XhtVOlsLjK&md5=bd590c9714d6ee14bf3fe4829feb0cf9CAS |

García-Díaz, E. C., Gómez-Quiroz, L. E., Arenas-Ríos, E., Aragón-Martínez, A., Ibarra-Arias, J. A., and del Socorro, I. R.-M. M. (2015). Oxidative status in testis and epididymal sperm parameters after acute and chronic stress by cold-water immersion in the adult rat. Syst Biol Reprod Med 61, 150–160.
Oxidative status in testis and epididymal sperm parameters after acute and chronic stress by cold-water immersion in the adult rat.CrossRef |

Garrel, C., Alessandri, J. M., Guesnet, P., and Al-Gubory, K. H. (2012). Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development. Int. J. Biochem. Cell Biol. 44, 123–131.
Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development.CrossRef | 1:CAS:528:DC%2BC3MXhs1CrsbzK&md5=f7c2fd38e057147a1102236c3e686f11CAS |

Giannattasio, A., Girotti, M., Williams, K., Hall, L., and Bellastella, A. (1997). Puberty influences expression of phospholipid hydroperoxide glutathione peroxidase (GPX4) in rat testis: probable hypophysis regulation of the enzyme in male reproductive tract. J. Endocrinol. Invest. 20, 439–444.
Puberty influences expression of phospholipid hydroperoxide glutathione peroxidase (GPX4) in rat testis: probable hypophysis regulation of the enzyme in male reproductive tract.CrossRef | 1:CAS:528:DyaK2sXntlGhurw%3D&md5=2842a37c1134bbb3d03357dae7cd0cd5CAS |

González, O., Tobia, C., Ebersole, J., and Novak, M. J. (2012). Caloric restriction and chronic inflammatory diseases. Oral Dis. 18, 16–31.
Caloric restriction and chronic inflammatory diseases.CrossRef |

Guerriero, G., Trocchia, S., Abdel-Gawad, F. K., and Ciarcia, G. (2014). Roles of reactive oxygen species in the spermatogenesis regulation. Front. Endocrinol. (Lausanne) 5, 56.
Roles of reactive oxygen species in the spermatogenesis regulation.CrossRef |

Horváthová, F., Danielisová, V., Domoráková, I., Solár, P., Rybárová, S., Hodorová, I., and Mihalik, J. (2016). The effect of R-(-)-deprenyl administration on antioxidant enzymes in rat testis. Eur. J. Pharmacol. 788, 21–28.
The effect of R-(-)-deprenyl administration on antioxidant enzymes in rat testis.CrossRef |

Hou, M., Chu, Z., Liu, T., Lv, H., Sun, L., Wang, B., Huang, J., and Yan, W. (2015). A high-fat maternal diet decreases adiponectin receptor-1 expression in offspring. J. Matern. Fetal Neonatal Med. 28, 216–221.
A high-fat maternal diet decreases adiponectin receptor-1 expression in offspring.CrossRef | 1:CAS:528:DC%2BC2MXhsF2qsQ%3D%3D&md5=7bb37a8d82e4994814a9301e61cb1a3dCAS |

Judge, S., Jang, Y. M., Smith, A., Hagen, T., and Leeuwenburgh, C. (2005). Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J. 19, 419–421.
| 1:CAS:528:DC%2BD2MXit1Klu7g%3D&md5=c9b319f281e5cb0cfd271828100fa9f1CAS |

Katib, A. (2015). Mechanisms linking obesity to male infertility. Cent. European J. Urol. 68, 79–85.
Mechanisms linking obesity to male infertility.CrossRef | 1:CAS:528:DC%2BC28XpsFyrt7k%3D&md5=d2b93cf322b44c4cc53d3b7af75380d2CAS |

Kilcoyne, K. R., Smith, L. B., Atanassova, N., Macpherson, S., McKinnell, C., van den Driesche, S., Jobling, M. S., Chambers, T. J., De Gendt, K., Verhoeven, G., O’Hara, L., Platts, S., Renato de Franca, L., Lara, N. L., Anderson, R. A., and Sharpe, R. M. (2014). Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells. Proc. Natl. Acad. Sci. USA 111, E1924–E1932.
Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells.CrossRef | 1:CAS:528:DC%2BC2cXmslaqtr4%3D&md5=92fa6176e495b565ba50f447200fdd5dCAS |

Klenov, V. E., and Jungheim, E. S. (2014). Obesity and reproductive function: a review of the evidence. Curr. Opin. Obstet. Gynecol. 26, 455–460.
Obesity and reproductive function: a review of the evidence.CrossRef |

Ko, E. Y., Sabanegh, E. S., and Agarwal, A. (2014). Male infertility testing: reactive oxygen species and antioxidant capacity. Fertil. Steril. 102, 1518–1527.
Male infertility testing: reactive oxygen species and antioxidant capacity.CrossRef | 1:CAS:528:DC%2BC2cXhvF2htLfI&md5=a9300fa09e9f64cb3dbb00b930778d7eCAS |

Kodydková, J., Vávrová, L., Kocík, M., and Žák, A. (2014). Human catalase, its polymorphisms, regulation and changes of its activity in different diseases. Folia Biol. (Praha) 60, 153–167.

Lee, H. C., and Wei, Y. H. (2012). Mitochondria and aging. Adv. Exp. Med. Biol. 942, 311–327.
Mitochondria and aging.CrossRef | 1:CAS:528:DC%2BC38Xhs1GltrzF&md5=1e33f9dbdfc13aff6d4f370559dc7e83CAS |

Li, M., Reynolds, C. M., Segovia, S. A., Gray, C., and Vickers, M. H. (2015). Developmental programming of nonalcoholic fatty liver disease: the effect of early life nutrition on susceptibility and disease severity in later life. BioMed Res. Int. 2015, 437107.

Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–408.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.CrossRef | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=27001fc4d390214adec9d2e6245c9fd6CAS |

Macanovic, B., Vucetic, M., Jankovic, A., Stancic, A., Buzadzic, B., Garalejic, E., Korac, A., Korac, B., and Otasevic, V. (2015). Correlation between sperm parameters and protein expression of antioxidative defense enzymes in seminal plasma: a pilot study. Dis. Markers 2015, 436236.
Correlation between sperm parameters and protein expression of antioxidative defense enzymes in seminal plasma: a pilot study.CrossRef |

Mahizir, D., Briffa, J. F., Hryciw, D. H., Wadley, G. D., Moritz, K. M., and Wlodek, M. E. (2016). Maternal obesity in females born small: pregnancy complications and offspring disease risk. Mol. Nutr. Food Res. 60, 8–17.
Maternal obesity in females born small: pregnancy complications and offspring disease risk.CrossRef | 1:CAS:528:DC%2BC2MXht12msb3N&md5=c3b2a0de4719a5921b982265c1798f27CAS |

Marques, C., Meireles, M., Norberto, S., Leite, J., Freitas, J., Pestana, D., Faria, A., and Calhau, C. (2016). High-fat diet-induced obesity rat model: a comparison between Wistar and Sprague-Dawley rat. Adipocyte 5, 11–21.
High-fat diet-induced obesity rat model: a comparison between Wistar and Sprague-Dawley rat.CrossRef | 1:CAS:528:DC%2BC28XmtFamtb0%3D&md5=af64cb8990c1ae035ba04a56e280365cCAS |

Mortazavi, M., Salehi, I., Alizadeh, Z., Vahabian, M., and Roushandeh, A. M. (2014). Protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. J. Reprod. Infertil. 15, 22–28.
| 1:CAS:528:DC%2BC2cXht1Wru7%2FP&md5=4a99c1895228f65fb4b8b32bd6a1a61bCAS |

Niederberger, C. (2013). Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. J. Urol. 189, 257.

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 |

Reame, V., Pytlowanciv, E. Z., Ribeiro, D. L., Pissolato, T. F., Taboga, S. R., Goes, R. M., and Pinto-Fochi, M. E. (2014). Obesogenic environment by excess of dietary fats in different phases of development reduces spermatic efficiency of wistar rats at adulthood: correlations with metabolic status. Biol. Reprod. 91, 151.
Obesogenic environment by excess of dietary fats in different phases of development reduces spermatic efficiency of wistar rats at adulthood: correlations with metabolic status.CrossRef |

Rodríguez-González, G. L., Vega, C. C., Boeck, L., Vázquez, M., Bautista, C. J., Reyes-Castro, L. A., Saldaña, O., Lovera, D., Nathanielsz, P. W., and Zambrano, E. (2015). Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility. Int. J. Obes. 39, 549–556.
Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility.CrossRef |

Sahoo, D. K., Roy, A., and Chainy, G. B. (2008). Rat testicular mitochondrial antioxidant defence system and its modulation by aging. Acta Biol. Hung. 59, 413–424.
Rat testicular mitochondrial antioxidant defence system and its modulation by aging.CrossRef | 1:STN:280:DC%2BD1M%2FmtlCruw%3D%3D&md5=d683ea6c827cb9ceefbf6a527fed78b6CAS |

Salomon, T. B., Hackenhaar, F. S., Almeida, A. C., Schuller, A. K., Gil Alabarse, P. V., Ehrenbrink, G., and Benfato, M. S. (2013). Oxidative stress in testis of animals during aging with and without reproductive activity. Exp. Gerontol. 48, 940–946.
Oxidative stress in testis of animals during aging with and without reproductive activity.CrossRef | 1:CAS:528:DC%2BC3sXhtlSht77K&md5=787d603fc1e2fdb04e89cfb457cd8df1CAS |

Santos, M., Rodriguez-Gonzalez, G. L., Ibanez, C., Vega, C. C., Nathanielsz, P. W., and Zambrano, E. (2015). Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308, R219–R225.
Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats.CrossRef | 1:CAS:528:DC%2BC2MXjsVKlsr8%3D&md5=16c574ddd47ee2185bea4c4e46389668CAS |

Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., Neumuller, C., Deutsch, M. J., Walch, A., Hrabe de Angelis, M., Wurst, W., Ursini, F., Roveri, A., Maleszewski, M., Maiorino, M., and Conrad, M. (2009). Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J. 23, 3233–3242.
Mitochondrial glutathione peroxidase 4 disruption causes male infertility.CrossRef | 1:CAS:528:DC%2BD1MXhtFagsrbE&md5=dbd8228de708fd562f78258576fbcaa6CAS |

Segovia, S. A., Vickers, M. H., Gray, C., and Reynolds, C. M. (2014). Maternal obesity, inflammation, and developmental programming. Biomed. Res. Int. 2014, 418975.

Shafik, A., and Olfat, S. (1981). Lipectomy in the treatment of scrotal lipomatosis. Br. J. Urol. 53, 55–61.
Lipectomy in the treatment of scrotal lipomatosis.CrossRef | 1:STN:280:DyaL3M7jsVygsg%3D%3D&md5=365628ac0bf53142454be428c7a6e4d7CAS |

Shukla, K. K., Chambial, S., Dwivedi, S., Misra, S., and Sharma, P. (2014). Recent scenario of obesity and male fertility. Andrology 2, 809–818.
Recent scenario of obesity and male fertility.CrossRef | 1:CAS:528:DC%2BC2cXhsl2htbjL&md5=ca1c19838c1c50e66c871115ee260b7dCAS |

Sikka, S. C. (2001). Relative impact of oxidative stress on male reproductive function. Curr. Med. Chem. 8, 851–862.
Relative impact of oxidative stress on male reproductive function.CrossRef | 1:CAS:528:DC%2BD3MXjsVChuro%3D&md5=10dea26762bca265cabafec4e1575d46CAS |

Sloboda, D. M., Howie, G. J., Pleasants, A., Gluckman, P. D., and Vickers, M. H. (2009). Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat. PLoS One 4, e6744.
Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat.CrossRef |

Sohal, R. S. (2002). Role of oxidative stress and protein oxidation in the aging process. Free Radic. Biol. Med. 33, 37–44.
Role of oxidative stress and protein oxidation in the aging process.CrossRef | 1:CAS:528:DC%2BD38XkslKjsrs%3D&md5=f52cce3b8ad9eb991d546c4ac209ac98CAS |

Stuart, J. A., Maddalena, L. A., Merilovich, M., and Robb, E. L. (2014). A midlife crisis for the mitochondrial free-radical theory of aging. Longev. Healthspan 3, 4.
A midlife crisis for the mitochondrial free-radical theory of aging.CrossRef |

Talton, O. O., Pennington, K. A., Pollock, K. E., Bates, K., Ma, L., Ellersieck, M. R., and Clamon Schulz, L. (2016). Maternal hyperleptinemia improves offspring insulin sensitivity in mice. Endocrinology 157, 2636–2648.
Maternal hyperleptinemia improves offspring insulin sensitivity in mice.CrossRef | 1:CAS:528:DC%2BC28XhslejsLrJ&md5=e5b6659c2a75768395ab3a8e4deb6bc1CAS |

Tanvig, M. (2014). Offspring body size and metabolic profile – effects of lifestyle intervention in obese pregnant women. Dan. Med. J. 61, B4893.

Ufer, C., and Wang, C. C. (2011). The roles of glutathione peroxidases during embryo development. Front. Mol. Neurosci. 4, 12.
| 1:CAS:528:DC%2BC38XovVKg&md5=623947f842893a99af86f690a5a70a93CAS |

Vega, C. C., Reyes-Castro, L. A., Bautista, C. J., Larrea, F., Nathanielsz, P. W., and Zambrano, E. (2015). Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism. Int. J. Obes. 39, 712–719.
Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism.CrossRef | 1:CAS:528:DC%2BC3sXhsVynu7vM&md5=5224a37c5b4eaa2b0543a8f6c2e563c8CAS |

Yan, W. J., Mu, Y., Yu, N., Yi, T. L., Zhang, Y., Pang, X. L., Cheng, D., and Yang, J. (2015). Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet. J. Assist. Reprod. Genet. 32, 1097–1104.
Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet.CrossRef |

Zambrano, E., and Nathanielsz, P. W. (2013). Mechanisms by which maternal obesity programs offspring for obesity: evidence from animal studies. Nutr. Rev. 71, S42–S54.
Mechanisms by which maternal obesity programs offspring for obesity: evidence from animal studies.CrossRef |

Zini, A., and Schlegel, P. N. (1997). Expression of glutathione peroxidases in the adult male rat reproductive tract. Fertil. Steril. 68, 689–695.
Expression of glutathione peroxidases in the adult male rat reproductive tract.CrossRef | 1:STN:280:DyaK1c%2FgtVyiuw%3D%3D&md5=b7a8cc2192b1b3e75224cbea53220549CAS |



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