Testicular Cellular Interactions in Male Fertility

The testis is a highly organised organ in which diverse somatic and germ cells communicate through paracrine, mechanical and immune signals to sustain spermatogenesis and hormonal function. Sertoli cells form the seminiferous epithelium, nurturing germ cells and establishing the blood-testis barrier. Leydig cells in the interstitium synthesise testosterone under luteinising hormone control, modulating Sertoli cell support and peritubular myoid cell contractility. Peritubular myoid cells envelop seminiferous tubules, contributing to luminal sperm transport via coordinated contractions and secreting extracellular matrix elements that shape the spermatogonial stem cell niche. Resident immune cells and endothelial networks further influence local homeostasis, balancing immune privilege with inflammation-driven remodelling. Dynamic alterations in matrix composition, cellular senescence and danger-signal recognition can perturb cellular crosstalk, linking testicular microenvironment changes to infertility. Understanding these cellular interactions is essential for addressing global declines in male reproductive health and for developing targeted therapies.

Research from Nature Portfolio

Recent studies have elucidated the role of peritubular myoid cells in orchestrating sterile inflammation through pattern-recognition receptors. One investigation demonstrated that extracellular matrix components such as biglycan engage Toll-like receptor 2 on human peritubular cells, triggering cytokine release and contributing to testicular inflammation associated with impaired spermatogenesis. A proteomic and imaging analysis of replicative senescence in cultured human peritubular cells revealed a decline in mitochondrial networks, altered lysosomal content and deranged proteostasis, alongside elevated secretion of factors that may influence the spermatogonial stem cell niche. Complementary work has shown that extracellular ATP engages purinergic receptors on peritubular cells, driving pro-inflammatory cytokine production and linking mechanical signalling to innate immune surveillance in the testis.

Testicular Cellular Interactions in Male Fertility publication trend

The graph below shows the total number of articles in testicular cellular interactions in male fertility across all publications each year (not limited to Nature Index journals).

Technical terms

Sertoli cell: Somatic cell that supports germ-cell development, forms the blood-testis barrier and mediates nutritional and paracrine signals.

Leydig cell: Interstitial endocrine cell that produces testosterone, regulating spermatogenesis and secondary sexual characteristics.

Peritubular myoid cell: Smooth muscle-like cell surrounding seminiferous tubules, involved in sperm transport, extracellular matrix secretion and immune modulation.

Extracellular matrix (ECM): Network of proteins and glycoproteins providing structural support and biochemical cues within the testicular microenvironment.

Purinergic signalling: Cell communication pathway mediated by extracellular nucleotides such as ATP binding to P2 receptors.

Toll-like receptor 2 (TLR2): Pattern-recognition receptor that detects extracellular danger signals and activates inflammatory responses in somatic cells.

Replicative senescence: Permanent cell cycle arrest induced by cumulative stress and division-related damage, altering cell function and secretome.

References

1. Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells. Scientific Reports (2016).
2. Insights into replicative senescence of human testicular peritubular cells. Scientific Reports (2019).
3. ATP-mediated Events in Peritubular Cells Contribute to Sterile Testicular Inflammation. Scientific Reports (2018).
4. Cyto- and Histopographic Assessment of CPA3-Positive Testicular Mast Cells in Obstructive and Non-Obstructive Azoospermia. Cells (2024).
5. Biogenic amines in the testis: sources, receptors and actions. Frontiers in Endocrinology (2024).
6. ATP activation of peritubular cells drives testicular sperm transport. eLife (2021).