Public PhD Defence Inne Xhonneux
The interaction of pre- and postnatal obesogenic environments in affecting daughter’s metabolic health and oocyte quality: fundamental insights for sustainable advice.
It is our pleasure to invite you for the public PhD defence of Inne Xhonneux on Thursday 12th December 2024 at 5pm.
Abstract
Maternal diet induced obesity (DIO) affects oocyte mitochondrial functions, reducing the quality of the oocyte and subsequent embryo. Further embryonic development in the oviduct and uterus of DIO mothers may reprogram the offspring, a process that continues during lactation. This may increase the offspring’s sensitivity to an obesogenic (OB) diet, exacerbating the direct effects of an OB diet on offspring health and oocyte quality. However, this was never thoroughly investigated. It also remains unknown whether the impact on offspring’s fertility is only apparent at fertile age or may already be inborn. Such information is crucial to determine the need to mitigate or protect against maternal effects in offspring at risk, and to offer fundamental insights for sustainable advice.
We hypothesized that both offspring and maternal OB diets affect adult offspring health and oocyte quality. Moreover, we hypothesized that maternal DIO influences the direct impact of the offspring’s OB diet. We investigated mature oocytes, but also dormant ovarian follicles at adulthood and even earlier at weaning and at birth.
Outbred Swiss offspring from control and OB-fed mothers were weaned on control or OB diets for 7 weeks. At offspring adult age, we confirmed negative effects of the offspring’s OB diet on offspring health and oocyte quality, and showed for the first time that even the dormant primordial follicle pool is hampered by the offspring’s OB diet. Contrarily, maternal DIO did not hamper the offspring’s metabolic profile, or increased the offspring’s sensitivity to an OB diet, but improved their metabolic profile despite morphological alterations in muscle mitochondria. Furthermore, our data suggest that maternal DIO increases the offspring’s oocyte bioenergetic capacity, without signs that are indicative for damage in mature and primordial follicle oocytes. Maternal DIO also did not interact with the direct effect of the offspring’s OB diet. Offspring from DIO mothers had no increased cellular stress levels (Hsp70) in their primordial follicle oocytes at birth or at weaning, but had reduced TFAM expression which may regulate mtDNA replication. More prominent effects of maternal DIO were detected in offspring primordial follicle oocytes after lactation, of which functional implications on subsequent follicular development require further investigation.
Based on our data, it is unlikely that adult obese women born to obese mothers would require different preconception care strategies to improve their oocyte quality. However, the subtle maternal DIO-induced changes in the offspring’s oocyte bioenergetic capacity may suggest the need for personalized IVF media formulations.