The impact of maternal diet-induced obesity on offspring primordial oocyte mitochondria at birth and at weaning.

Abstract

Maternal diet-induced obesity (DIO) may affect adult offspring oocyte quality due to mitochondrial dysfunction. Here, we investigated whether offspring of DIO mothers exhibit mitochondrial abnormalities in their primordial follicle oocytes (PFOs) already at birth and if (further) alterations can be detected at weaning. Female Swiss mice were fed a control or obesogenic diet for 7 weeks before mating and throughout pregnancy and lactation. Offspring ovaries were collected at birth and at weaning. Offspring PFOs were examined by transmission electron microscopy of ovarian sections. Key markers of cell stress (HSP70), mitochondrial biogenesis (PGC-1α), mtDNA replication (TFAM), fusion (MFN2, OPA1), and fission (DRP1) were examined using immunofluorescence and confocal microscopy. Maternal DIO did not alter HSP70 or PGC-1α expression in the PFOs at birth, suggesting that cellular homeostasis and mitochondrial biogenesis were unaffected. TFAM expression was reduced at both time points. DRP1 and cytoplasmic OPA1 expression were reduced at birth, but without ultrastructural changes in mitochondrial shape and density, suggesting that these alterations are regulatory. No inborn mitochondrial structural abnormalities could be detected. In contrast, at weaning, offspring born to and nursed by DIO mothers exhibited a high number of lipid droplets (LDs) in their ovaries, some of which were detectable in the PFOs, while no LDs were detected in the PFOs of the controls. Maternal DIO increased PGC-1α expression, suggesting postnatal effects on PFO mitochondrial biogenesis. MFN2 and OPA1 expression also increased, together with increased mitochondrial elongation and a reduced mitochondrial density. Mitochondrial abnormalities, such as vacuolation, loose inner membranes, the number of detected autophagosomes, and signs of lipophagy, were also significantly increased by maternal DIO at weaning. In conclusion, the oocyte mitochondrial structural abnormalities previously reported in adult offspring from DIO mothers were not detected in the PFOs at birth. Significant changes in primordial follicles linked to maternal DIO were detected only at weaning.