Maternal high-fat diet during pregnancy and lactation affects factors that regulate cell proliferation and apoptosis in the testis of adult progeny

Helen Viotti; Daniel Cavestany; Graeme B. Martin; Mark H. Vickers; Deborah M. Sloboda; Graciela Pedrana

doi:10.1071/RD23082

RESEARCH ARTICLE (Open Access)

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Maternal high-fat diet during pregnancy and lactation affects factors that regulate cell proliferation and apoptosis in the testis of adult progeny

Helen Viotti

^A , Daniel Cavestany

^A , Graeme B. Martin

^B ^* , Mark H. Vickers

^C , Deborah M. Sloboda

^D ^E ^F ^G and Graciela Pedrana

^A

+ Author Affiliations

- Author Affiliations

^A Facultad de Veterinaria, Universidad de la República, Montevideo, Uruguay.

^B UWA School of Agriculture and Environment, and UWA Institute of Agriculture, University of Western Australia, Perth, WA, Australia.

^C Liggins Institute, University of Auckland, Auckland, New Zealand.

^D Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.

^E Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada.

^F Department of Pediatrics, McMaster University, Hamilton, ON, Canada.

^G Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.

^* Correspondence to: Graeme.Martin@uwa.edu.au

Handling Editor: Andrew Pask

Reproduction, Fertility and Development 36, RD23082 https://doi.org/10.1071/RD23082

Submitted: 8 May 2023 Accepted: 4 April 2024 Published online: 13 May 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Context

A maternal high-fat diet is thought to pose a risk to spermatogenesis in the progeny.

Aims

We tested whether a maternal high-fat diet would affect Sertoli cell expression of transcription factors (insulin-like growth factor I (IGF-I); glial-cell line-derived neurotrophic factor (GDNF); Ets variant 5 (ETV5)) and cell proliferation and apoptotic proteins, in the testis of adult offspring.

Methods

Pregnant rats were fed ad libitum with a standard diet (Control) or a high-fat diet (HFat) throughout pregnancy and lactation. After weaning, male pups were fed the standard diet until postnatal day 160. Males were monitored daily from postnatal day 34 to determine onset of puberty. On postnatal day 160, their testes were processed for morphometry and immunohistochemistry.

Key results

The HFat diet increased seminiferous-tubule diameter (P < 0.03), the numbers of Sertoli cells (P < 0.0001) and Ki-67-positive spermatogonia (P < 0.0006), and the areas immunostained for ETV5 (P < 0.0001), caspase-3 (P < 0.001) and Bcl-2 (P < 0.0001). By contrast, the HFat diet reduced the areas immunostained for IGF-I (P < 0.01) and GDNF (P < 0.0001).

Conclusions

A maternal high-fat diet alters the balance between spermatogonia proliferation and spermatid apoptosis.

Implications

A maternal high-fat diet seems to ‘program’ adult male fertility.

Keywords: apoptosis, cell proliferation, developmental programming, high-fat diet, rat, reproduction, Sertoli cell, spermatogenesis, testis.

References

Alves MG, Jesus TT, Sousa M, Goldberg E, Silva BM, Oliveira PF (2016) Male fertility and obesity: are ghrelin, leptin and glucagon-like peptide-1 pharmacologically relevant? Current Pharmaceutical Design 22, 783-791.
| Crossref | Google Scholar | PubMed |

Bautista CJ, Rodríguez-González GL, Morales A, Lomas-Soria C, Cruz-Pérez F, Reyes-Castro LA, Zambrano E (2017) Maternal obesity in the rat impairs male offspring aging of the testicular antioxidant defence system. Reproduction, Fertility and Development 29, 1950-1957.
| Crossref | Google Scholar | PubMed |

Billah MM, Khatiwada S, Lecomte V, Morris MJ, Maloney CA (2022) Ameliorating high-fat diet-induced sperm and testicular oxidative damage by micronutrient-based antioxidant intervention in rats. European Journal of Nutrition 61, 3741-3753.
| Crossref | Google Scholar | PubMed |

Campos-Silva P, Costa WS, Sampaio FJB, Gregorio BM (2018) Prenatal and/or postnatal high-fat diet alters testicular parameters in adult Wistar albino rats. Histology and Histopathology 33, 407-416.
| Crossref | Google Scholar | PubMed |

Eo J, Song H, Lim HJ (2012) Etv5, a transcription factor with versatile functions in male reproduction. Clinical and Experimental Reproductive Medicine 39, 41-45.
| Crossref | Google Scholar | PubMed |

Escott GM, de Castro AL, Jacobus AP, Loss ES (2014) Insulin and IGF-I actions on IGF-I receptor in seminiferous tubules from immature rats. Biochimica et Biophysica Acta (BBA) – Biomembranes 1838, 1332-1337.
| Crossref | Google Scholar | PubMed |

Greenbaum D, Colangelo C, Williams K, Gerstein M (2003) Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biology 4, 117.
| Crossref | Google Scholar | PubMed |

Griffeth RJ, Bianda V, Nef S (2014) The emerging role of insulin-like growth factors in testis development and function. Basic and Clinical Andrology 24, 12.
| Crossref | Google Scholar |

Howie GJ, Sloboda DM, Vickers MH (2012) Maternal undernutrition during critical windows of development results in differential and sex-specific effects on postnatal adiposity and related metabolic profiles in adult rat offspring. British Journal of Nutrition 108, 298-307.
| Crossref | Google Scholar |

Howie GJ, Sloboda DM, Reynolds CM, Vickers MH (2013) Timing of maternal exposure to a high fat diet and development of obesity and hyperinsulinemia in male rat offspring: same metabolic phenotype, different developmental pathways? Journal of Nutrition and Metabolism 2013, 517384.
| Crossref | Google Scholar |

Langley-Evans SC (2015) Nutrition in early life and the programming of adult disease: a review. Journal of Human Nutrition and Dietetics 28, 1-14.
| Crossref | Google Scholar |

Mao J, Pennington KA, Talton OO, Schulz LC, Sutovsky M, Lin Y, Sutovsky P (2018) In utero and postnatal exposure to high fat, high sucrose diet suppressed testis apoptosis and reduced sperm count. Scientific Reports 8, 7622.
| Crossref | Google Scholar | PubMed |

Meneghini MA, Galarza RA, Flores QJP, Faletti AG (2022) Diet-induced maternal obesity and overnutrition cause a decrease in the sperm quality of the offspring. The Journal of Nutritional Biochemistry 103, 108966.
| Crossref | Google Scholar | PubMed |

Morrow CMK, Hostetler CE, Griswold MD, Hofmann M-C, Murphy KM, Cooke PS, Hess RA (2007) ETV5 is required for continuous spermatogenesis in adult mice and may mediate blood–testes barrier function and testicular immune privilege. Annals of the New York Academy of Sciences 1120, 144-151.
| Crossref | Google Scholar | PubMed |

Murphy CJ, Richburg JH (2014) Implications of Sertoli cell induced germ cell apoptosis to testicular pathology. Spermatogenesis 4, e979110.
| Crossref | Google Scholar | PubMed |

Parekh PA, Garcia TX, Hofmann M-C (2019) Regulation of GDNF expression in Sertoli cells. Reproduction 157, R95-R107.
| Crossref | Google Scholar |

Pedrana G, Viotti H, Lombide P, Cavestany D, Martin GB, Vickers MH, Sloboda DM (2020) Maternal undernutrition during pregnancy and lactation affects testicular morphology, the stages of spermatogenic cycle, and the testicular IGF-I system in adult offspring. Journal of Developmental Origins of Health and Disease 11, 473-483.
| Crossref | Google Scholar |

Pedrana G, Larrañaga C, Diaz A, Viotti H, Lombide P, Cavestany D, Vickers MH, Martin GB, Sloboda DM (2021) Maternal undernutrition during pregnancy and lactation increases transcription factors, ETV5 and GDNF, and alters regulation of apoptosis and heat shock proteins in the testis of adult offspring in the rat. Reproduction, Fertility and Development 33, 484-496.
| Crossref | Google Scholar | PubMed |

Pinto-Fochi ME, Pytlowanciv EZ, Reame V, Rafacho A, Ribeiro DL, Taboga SR, Góes RM (2016) A high-fat diet fed during different periods of life impairs steroidogenesis of rat Leydig cells. Reproduction 152, 795-808.
| Crossref | Google Scholar |

Ramazi S, Zahiri J (2021) Post-translational modifications in proteins: resources, tools and prediction methods. Database 2021, baab012.
| Crossref | Google Scholar |

Rodrigo N, Saad S, Pollock C, Glastras SJ (2022) Diet modification before or during pregnancy on maternal and foetal outcomes in rodent models of maternal obesity. Nutrients 14, 2154.
| Crossref | Google Scholar | PubMed |

Rodríguez-González GL, Vega CC, Boeck L, Vázquez M, Bautista CJ, Reyes-Castro LA, Saldaña O, Lovera D, Nathanielsz PW, Zambrano E (2015) Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility. International Journal of Obesity 39, 549-556.
| Crossref | Google Scholar |

Rodríguez-González GL, de Los Santos S, Méndez-Sánchez D, Reyes-Castro LA, Ibáñez CA, Canto P, Zambrano E (2023) High-fat diet consumption by male rat offspring of obese mothers exacerbates adipose tissue hypertrophy and metabolic alterations in adult life. British Journal of Nutrition 130, 783-792.
| Crossref | Google Scholar | PubMed |

Ruiz Valderrama L, Cervantes RE, Fragoso I, Rodríguez Tobón A, González Márquez H, Arrieta I, Tarragó MR, Arteaga M, Arenas E (2016) Efecto de la obesidad en la fertilidad masculina. Estudios en modelos animales. Revista Iberoamericana de Ciencias. 1^a Jornadas de Reproducción UAM-Iztapalapa 3, 44-51.
| Google Scholar |

Schlesser HN, Simon L, Hofmann M-C, Murphy KM, Murphy T, Hess RA, Cooke PS (2008) Effects of ETV5 (ets variant gene 5) on testis and body growth, time course of spermatogonial stem cell loss, and fertility in mice. Biology of Reproduction 78, 483-489.
| Crossref | Google Scholar | PubMed |

Sertorio MN, César H, de Souza EA, Mennitti LV, Santamarina AB, De Souza Mesquita LM, Jucá A, Casagrande BP, Estadella D, Aguiar O, Jr, Pisani LP (2022) Parental high-fat high-sugar diet intake programming inflammatory and oxidative parameters of reproductive health in male offspring. Frontiers in Cell and Developmental Biology 10, 867127.
| Crossref | Google Scholar |

Shaha C, Tripathi R, Mishra DP (2010) Male germ cell apoptosis: regulation and biology. Philosophical Transactions of the Royal Society B: Biological Sciences 365, 1501.
| Crossref | Google Scholar |

Singh R, Letai A, Sarosiek K (2019) Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nature Reviews Molecular Cell Biology 20, 175-193.
| Crossref | Google Scholar | PubMed |

Sloboda DM, Howie GJ, Pleasants A, Gluckman PD, Vickers MH (2009) Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat. PLoS ONE 4, e6744.
| Crossref | Google Scholar | PubMed |

Tsoulis MW, Chang PE, Moore CJ, Chan KA, Gohir W, Petrik JJ, Vickers MH, Connor KL, Sloboda DM (2016) Maternal high-fat diet-induced loss of fetal oocytes is associated with compromised follicle growth in adult rat offspring. Biology of Reproduction 94, 1-11.
| Crossref | Google Scholar |

Tyagi G, Carnes K, Morrow C, Kostereva NV, Ekman GC, Meling DD, Hostetler C, Griswold M, Murphy KM, Hess RA, Hofmann M-C, Cooke PS (2009) Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis. Biology of Reproduction 81, 258-266.
| Crossref | Google Scholar | PubMed |

Vannelli BG, Barni T, Orlando C, Natali A, Serio M, Balboni GC (1988) Insulin-like growth factor-1 (IGF-I) and IGF-I receptor in human testis: an immunohistochemical study. Fertility and Sterility 49, 666-669.
| Crossref | Google Scholar |

Vautier AN, Cadaret CN (2022) Long-term consequences of adaptive fetal programming in ruminant livestock. Frontiers in Animal Science 3, 778440.
| Crossref | Google Scholar |

Williams L, Seki Y, Vuguin PM, Charron MJ (2014) Animal models of in utero exposure to a high fat diet: a review. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 1842, 507-519.
| Crossref | Google Scholar | PubMed |

Yang Y, Han C (2010) GDNF stimulates the proliferation of cultured mouse immature Sertoli cells via its receptor subunit NCAM and ERK1/2 signaling pathway. BMC Cell Biology 11, 78.
| Crossref | Google Scholar |

Zhang X, Zhao X, Li G, Zhang M, Xing P, Li Z, Chen B, Yang H, Wu Z (2021) Establishment of Etv5 gene knockout mice as a recipient model for spermatogonial stem cell transplantation. Biology Open 10, bio056804.
| Crossref | Google Scholar |