Growth Factor Signaling in Male Reproductive Physiology

Growth factors constitute a diverse group of signalling molecules that regulate male reproductive physiology through binding to corresponding receptors and activation of intracellular cascades. In the testis, paracrine and autocrine signalling by fibroblast growth factors (FGFs), nerve growth factor (NGF) and related ligands orchestrates the proliferation and differentiation of germ cells, Sertoli cells and Leydig cells. Receptor tyrosine kinases (RTKs) such as FGFRs and TrkA (the high-affinity NGF receptor) transduce extracellular cues into activation of pathways including PI3K/Akt and MAPK/ERK, governing cell survival, metabolism and motility. In mature spermatozoa, growth factor signalling modulates motility, capacitation and acrosome reaction, with implications for fertilisation potential and assisted reproduction. Dysregulation of these pathways is associated with infertility phenotypes such as asthenozoospermia, varicocele-induced damage and gonadal dysfunction. Emerging evidence highlights the potential to exploit growth factor signalling for therapeutic benefit—ranging from exogenous supplementation during sperm cryopreservation to modulation of the hypothalamic–pituitary–gonadal axis in hypogonadism. Together, these insights emphasise the global significance of growth factor networks in male fertility and lay the foundation for novel interventions in reproductive medicine.

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Growth Factor Signaling in Male Reproductive Physiology publication trend

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Technical terms

Growth factor: Protein that binds to specific receptors to regulate cell proliferation, differentiation and survival.

Receptor tyrosine kinase (RTK): Membrane receptor that phosphorylates tyrosine residues upon ligand binding, initiating intracellular signalling.

Neurotrophin: Family of growth factors that influence the development and function of neurons and non-neuronal cells, including NGF.

PI3K/Akt pathway: Intracellular signalling cascade promoting cell survival and metabolism, activated downstream of RTKs.

MAPK pathway: Signalling cascade involving mitogen-activated protein kinases that regulates cell proliferation and differentiation.

References

1. A Possible Role for Nerve Growth Factor and Its Receptors in Human Sperm Pathology. Biomedicines (2023).
2. Effect of nerve growth factor on sperm quality in asthenozoosprmic men during cryopreservation. Reproductive Biology and Endocrinology (2016).
3. NGF and the Male Reproductive System: Potential Clinical Applications in Infertility. International Journal of Molecular Sciences (2022).
4. The Roles of Fibroblast Growth Factors in the Testicular Development and Tumor. Journal of Diabetes Research (2013).
5. The Hepatokine FGF21 Increases the Human Spermatozoa Motility. Frontiers in Endocrinology (2022).