Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice

Fullston, Tod; Palmer, Nicole O.; Owens, Julie A.; Mitchell, Megan; Bakos, Hassan W.; Lane, Michelle

doi:10.1093/humrep/des030

Cited by 181 publications

(214 citation statements)

References 38 publications

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“…62 While fathers cannot provide direct nourishment to the young after birth, additional attention should be paid to whether a healthy diet of the father, and the mother, before conception can lead to long-term beneficial offspring consequences. It is increasingly becoming apparent that sub-optimal paternal diets, those high in fat or protein restricted, can result in negative offspring sequelae, [14][15][16][17][18][19][20][21][146][147][148][149] but the impacts of a healthy diet have been largely ignored. In conclusion, much work remains on identifying various steps that both parents can adapt to ensure the lifelong health of their offspring and potentially even triumph over negative influences that the conceptus or neonate may encounter.…”

Section: Discussionmentioning

confidence: 99%

Homage to the ‘H’ in developmental origins of health and disease

Rosenfeld

2016

J Dev Orig Health Dis

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Abundant evidence exists linking maternal and paternal environments from pericopconception through the postnatal period to later risk to offspring diseases. This concept was first articulated by the late Sir David Barker and as such coined the Barker Hypothesis. The term was then mutated to Fetal Origins of Adult Disease and finally broadened to developmental origins of adult health and disease (DOHaD) in recognition that the perinatal environment can shape both health and disease in resulting offspring. Developmental exposure to various factors, including stress, obesity, caloric-rich diets and environmental chemicals can lead to detrimental offspring health outcomes. However, less attention has been paid to date on measures that parents can take to promote the long-term health of their offspring. In essence, have we neglected to consider the ‘H’ in DOHaD? It is the ‘H’ component that should be of primary concern to expecting mothers and fathers and those seeking to have children. While it may not be possible to eliminate exposure to all pernicious factors, prevention/remediation strategies may tip the scale to health rather than disease. By understanding disruptive DOHaD mechanisms, it may also illuminate behavioral modifications that parents can adapt before fertilization and throughout the neonatal period to promote the lifelong health of their male and female offspring. Three possibilities will be explored in the current review: parental exercise, probiotic supplementation and breastfeeding in the case of mothers. The ‘H’ paradigm should be the focus going forward as a healthy start can indeed last a lifetime.

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Section: Discussionmentioning

confidence: 99%

Homage to the ‘H’ in developmental origins of health and disease

Rosenfeld

2016

J Dev Orig Health Dis

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“…This was evident as a reduction in meiotic progression, increased oocyte arrest and altered mitochondrial function at 17 weeks of age, despite the offspring being fed a CD [16]. When mated to normal weight males, these females also give birth to F2 offspring who themselves have impaired metabolic and reproductive function [15,16].…”

Section: Tod Fullston and Helana Shehadeh Contributed Equally To Thismentioning

confidence: 99%

“…The perturbed reproductive health of female offspring sired by obese fathers was initially characterized by impaired oocyte maturation and impaired mitochondrial function at 17 weeks of age [16]. But the ability of these offspring to produce developmentally competent embryos and quality of their resultant embryos are not known for a much earlier age that predates any metabolic disturbances (i.e., 5 weeks of age).…”

Section: Tod Fullston and Helana Shehadeh Contributed Equally To Thismentioning

confidence: 99%

Female offspring sired by diet induced obese male mice display impaired blastocyst development with molecular alterations to their ovaries, oocytes and cumulus cells

Fullston

Shehadeh

Sandeman

et al. 2015

J Assist Reprod Genet

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Purpose To investigate the impacts that a paternal high fat diet (HFD) has on embryology, ovarian/cumulus cell gene expression and COC metabolism from female offspring, using a mouse model. Methods Founder male mice were either fed a control diet (CD) or a HFD for 12 weeks. The HFD induced obesity but not diabetes, and founder males were then mated to normal weight CD fed female mice. Female offspring were maintained on a CD, super-ovulated, mated and the resultant zygotes were cultured to the blastocyst stage for embryo morphology, blastocyst cell number and apoptosis assessment. Ovaries and cumulus cells from offspring were collected for gene expression analysis of selected genes that maintain chromatin remodeling and endoplasmic reticulum (ER), metabolic and inflammatory homeostasis. Cumulus/oocyte complexes were also investigated for glucose uptake and lipid accumulation. Results Female offspring sired by obese fathers produced embryos with delayed development and impaired quality, displayed increases in ovarian expression of Glut1, Glut3 and Glut4, and an increase in cumulus cell expression of Glut4. Interestingly their COCs did take up more glucose, but did accumulate more lipid. Conclusions A paternal HFD is associated with subfertility in female offspring despite the offspring being fed a CD and this subfertility is concomitant with ovarian/cumulus cell molecular alterations and increased lipid accumulation.

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“…24,25 A number of studies have reported that a parental diet containing high fat or imposing calorie restriction modulates the phenotype of the offspring. [26][27][28] Under-nourishment in utero leads to methylome changes in the sperm of the male progeny and metabolic changes that are inherited to the subsequent generation. 29 A high fat paternal diet in rodents changes the insulin and glucose levels in offspring serum and induces an abnormal response after glucose or insulin injections.…”

Section: Introductionmentioning

confidence: 99%

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

et al. 2015

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Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.

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Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice

Abstract: This is the first observation of paternal transmission of diminished reproductive health to future generations and could have significant implications for the transgenerational amplification of subfertility observed worldwide in humans.

Cited by 181 publications

References 38 publications

Homage to the ‘H’ in developmental origins of health and disease

Homage to the ‘H’ in developmental origins of health and disease

Female offspring sired by diet induced obese male mice display impaired blastocyst development with molecular alterations to their ovaries, oocytes and cumulus cells

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

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