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.

The influence ofin vitrofertilization and embryo culture on the embryo epigenetic constituents and the possible consequences in the bovine model

“…23 Studies in the mouse are showing that the mother's metabolic status at the time of conception may impact the metabolic profile of the next generation and also the ovarian reserve and physiology. 24 A similar phenomenon was also described in cows by Walsh et al 25 and was also demonstrated in rats. 26 The reduced energy diet around conception and for 100 days post artificial insemination (AI) resulted in heifer calves with diminished ovarian reserves at 2 years of age 27 and potentially reduced fertility.…”

The transgenerational effect of maternal and paternal F1 low birth weight on bone health of second and third generation offspring

“…32 F1 female mice, born to diet-induced obese fathers, had disrupted fertility with altered ovarian genes and delayed embryo development. 33 These studies confirm the transmission of disease across generations and in a specific manner of mode of transmission. It is clear in the present study there is no transmission of poor bone health to female offspring via the paternal line.…”

Maternal transmission of mitochondrial diseases

“…Apart from mtDNA mutations, mitochondrial damage in oocytes has also been linked with increased risk of metabolic diseases in offspring. Obesity leads to increased lipid content in the follicular fluid, cumulus cells, and oocytes, which in turn damage organelles such as mitochondria and the ER (Wang et al, 2009;Wu et al, 2010;Fullston et al, 2015;Ruebel et al, 2017). Impaired ER function can lead to activation of the unfolded protein response (UPR) and Ca +2 release, further disrupting mitochondrial function (i.e., decreased Dym and increased ROS) and oocyte homeostasis (Wu et al, 2010(Wu et al, , 2015Luzzo et al, 2012;Hou et al, 2016).…”