Peroxisome Proliferator-Activated Receptor Signaling in Male Reproductive Physiology

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that orchestrate lipid metabolism, energy homeostasis and cellular differentiation. In the male reproductive system, PPAR subtypes (α, β/δ and γ) are expressed in Leydig cells, Sertoli cells, germ cells and mature spermatozoa. Activation of PPARα and PPARγ modulates fatty acid uptake and β-oxidation in Leydig cells, thereby influencing steroidogenic enzyme expression and testosterone biosynthesis. In Sertoli cells, PPARβ/δ signalling supports cholesterol efflux and glycolytic flux, processes essential for nourishing developing germ cells. In germ cells, PPARγ drives lipid droplet formation and reactive oxygen species detoxification, protecting spermatogenic integrity. In mature spermatozoa, PPARγ contributes to mitochondrial respiration and motility, linking metabolic competence to fertilisation capacity. Dysregulation of PPAR pathways by environmental ligands, metabolic syndrome or endocrine disruptors can impair steroidogenesis, compromise the blood–testis barrier and reduce sperm quality. Ongoing research seeks to exploit selective PPAR modulators to restore reproductive function in men affected by obesity, diabetes or chemical exposures, underscoring the global significance of nuclear receptor signalling in fertility management.

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Peroxisome Proliferator-Activated Receptor Signaling in Male Reproductive Physiology publication trend

The graph below shows the total number of articles in peroxisome proliferator-activated receptor signaling in male reproductive physiology across all publications each year (not limited to Nature Index journals).

Technical terms

Peroxisome proliferator-activated receptor (PPAR): A family of nuclear receptors (α, β/δ, γ) that regulate gene networks controlling lipid metabolism, energy balance and cellular differentiation.

Leydig cell: Testicular cells that synthesise testosterone in response to luteinising hormone, central to male secondary sexual characteristics and spermatogenesis.

Sertoli cell: Somatic cells in the seminiferous epithelium that support and nourish developing germ cells and maintain the blood–testis barrier.

Spermatogenesis: The multi-stage process by which diploid spermatogonia develop into mature haploid spermatozoa within the seminiferous tubules.

Transcription factor: A protein that binds specific DNA sequences to regulate the transcription of genetic information from DNA to messenger RNA.

References

1. Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPARγ. Journal of Biological Chemistry (2023).
2. The Pregnane-X receptor regulates steroid synthesis in mouse Leydig cells. Frontiers in Endocrinology (2025).
3. Regulation of Male Fertility by the Renin-Angiotensin System. International Journal of Molecular Sciences (2020).