Single-cell and spatial transcriptomes reveal the impact of maternal low protein diet on follicular cell composition and ovarian micro-environment in the offspring.

Abstract

Maternal low protein diet around pregnancy reduces the primordial follicles in offspring ovary. Resolving cellular and molecular mechanisms associated with low protein diet is therefore urgently needed for the guidance of dietary interventions. Here, we utilized single-cell and spatial RNA-seq to create transcriptomic atlases of offspring ovaries from maternal low protein diet mice. Analysis of cell type specific low protein diet associated transcriptional changes revealed increased unfolded protein and decreased oxidative phosphorylation defense as a hallmark of low protein diet effects. Altered pathways included hedgehog signaling in granulosa cells, BMP signaling in theca cells and PTN signaling in early theca cells. Notably, the disordered follicular cell function and ovarian microenvironment may closely corelated with decreased follicular number and quality. Collectively, our findings depict the transcriptomic atlases of the offspring ovary derived from maternal low protein diet group and provide candidate molecular mechanisms underlying the complex ovarian cell changes conferred by low protein diet.