Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Fullston T

PROVIDER: S-EPMC4429434 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Publications

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

Fullston Tod T Shehadeh Helana H Sandeman Lauren Y LY Kang Wan Xian WX Wu Linda L LL Robker Rebecca L RL McPherson Nicole O NO Lane Michelle M

Journal of assisted reproduction and genetics 20150409 5

<h4>Purpose</h4>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.<h4>Methods</h4>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 cu ...[more]

PMID: 25854657

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Project description:BackgroundMaternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO.HypothesisMO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx in part prevents these outcomes.MethodsF0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day 90 of life through pregnancy beginning day 120) providing four groups (n=8/group)--(i) controls, (ii) obese, (iii) exercised controls and (iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed.ResultsExercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially increases glucose, insulin, cholesterol and oxidative stress. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 offspring weights were similar at birth. At PND 36, MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls, exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise.ConclusionsMEx before and during pregnancy has beneficial effects on the maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status.

Project description:Study questionIs relative mitochondrial DNA (mtDNA) content in cumulus cells (CCs) related to embryo developmental competence in humans and/or the bovine model?Summary answermtDNA content in CCs provides a poor predictive value of oocyte developmental potential, both in vitro and following embryo transfer.What is known alreadyCCs are closely connected to the oocyte through transzonal projections, serving essential metabolic functions during folliculogenesis. These oocyte-supporting cells are removed and discarded prior to ICSI, thereby providing interesting biological material on which to perform molecular analyses designed to identify markers that predict oocyte developmental competence. Previous studies have positively associated oocyte mtDNA content with developmental potential in animal models and women. However, it remains debatable whether mtDNA content in CCs could be used as a proxy to infer oocyte developmental potential.Study design size durationmtDNA content was analyzed in CCs obtained from 109 human oocytes unable to develop to blastocyst, able to develop to blastocyst but failing to establish pregnancy or able to develop to blastocyst and to establish pregnancy. mtDNA analysis was also performed on bovine cumulus samples collected from 120 oocytes unable to cleave, oocytes developing into cleaved embryos but arresting development prior to the blastocyst stage or oocytes developing to blastocysts.Participants/materials setting methodsHuman CCs samples were obtained from women undergoing IVF. Only unfrozen oocytes and embryos not submitted to preimplantation genetic testing were included in the analysis. Bovine samples were obtained from slaughtered cattle and individually matured, fertilized and cultured in vitro. Relative mtDNA was assessed by quantitative PCR analysis.Main results and the role of chancemtDNA content in human and bovine CCs did not differ according to the developmental potential of their enclosed oocyte. Moreover, mtDNA content in bovine oocytes did not correlate with that of their corresponding CCs.Large scale dataN/A.Limitations reasons for cautionThe lack of correlation found between mtDNA content in human CCs and oocytes was also assessed in bovine samples. Although bovine folliculogenesis, mono-ovulatory ovulation and early embryo development exhibit considerable similarities with that of humans, they may not be fully comparable.Wider implications of the findingsThe use of molecular markers for oocyte developmental potential in CCs could be used to enhance success rates following single embryo transfer. However, our data indicate that mtDNA in CCs is not a good proxy for oocyte quality.Study funding/competing interestsThis research was supported by the Industrial Doctorate Project IND2017/BIO-7748 funded by the Madrid Region Government. The authors declare no competing interests.

Project description:BACKGROUND: Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis. METHODOLOGY/PRINCIPAL FINDING: Immature human oocytes were matured in vitro via supplementation with ovarian paracrine/autocrine factors that were selected based on expression of ligands in the cumulus cells and their corresponding receptors in oocytes. Matured oocytes were artificially activated to assess developmental competence. Gene expression profiles of parthenotes were compared to IVF/ICSI embryos at morula and blastocyst stages. Following incubation in medium supplemented with ovarian factors (BDNF, IGF-I, estradiol, GDNF, FGF2 and leptin), a greater percentage of oocytes demonstrated nuclear maturation and subsequently, underwent parthenogenesis relative to control. Similarly, cytoplasmic maturation was also improved as indicated by development to blastocyst stage. Parthenogenic blastocysts exhibited mRNA expression profiles similar to those of blastocysts obtained after IVF/ICSI with the exception for MKLP2 and PEG1. CONCLUSIONS/SIGNIFICANCE: Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer.

Dataset Information

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

Purpose

Methods

Results

Conclusions

Publications

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

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