Macrophages Play Unexpected Role in Sperm Production

Published August 18, 2015
Cell Reports

Macrophages are white blood cells best known for their role in engulfing and digesting harmful microbes, cell debris, and other foreign particles. However, these cellular scavengers also play a surprising role in the cycle of sperm production.

The latest findings from a research team led by Tony DeFalco, PhD, were striking enough to be featured on the Aug. 18, 2015, cover of Cell Reports. The journal Biology of Reproduction also included the study in its “World of Reproductive Biology” collection of breakthrough findings.

Despite earlier success in simpler fruit flies and roundworms, scientists have spent years hunting for the niche within more complex mammalian testes, where stem cells begin the cycle of sperm production. In a series of experiments with mice, DeFalco and colleagues found an unexpected answer.

Their work describes a macrophage population located at the surface of seminiferous tubules in the adult mouse. These unusual, small-bodied macrophages appear to contribute to a niche that supports sperm stem cell differentiation.

When the team ablated these macrophages, stem cells in the mice testes produced far fewer daughter cells. Macrophage presence appears to be required specifically for Asingle spermatogonia to differentiate into A-aligned spermatogonia.

These findings shed new light on the potential causes of male infertility, and may eventually lead to improved treatments. “Macrophages have largely been overlooked in reproductive contexts,” DeFalco says.

However, the discovery has implications beyond reproduction.

“Immune cells interact with other cell types during organ formation and secrete factors critical for growth, development, and homeostasis," DeFalco says. "This unexpected role for macrophages in the spermatogonial niche further supports the idea that macrophages may be broadly important in regulating stem cell populations.”

Fig A:  New research published in Cell Reports describes how macrophages influence sperm cell production in mammalian testes. This illustration shows that macrophages are enriched near sperm cell precursors and are required for sperm stem cell differentiation, potentially acting through CSF1 and retinoic acid pathways.
Click image to view caption.

Citation

DeFalco T, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis. Cell Rep. 2015 Aug 18;12(7):1107-19.