مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Stem Cell Signaling in Reproductive Medicine: Potential for Treating Infertility
Stem Cell Signaling in Reproductive Medicine: Potential for Treating Infertility
Leila Hatami-Baroogh,1Vahid Asghariazar,2,*
1. Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. 2. Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Introduction: Infertility is a complex condition that affects nearly 15% of couples worldwide, representing a major clinical and social challenge. Despite significant progress in assisted reproductive technologies (ART), many cases remain unresolved, highlighting the urgent need for innovative therapeutic strategies. Stem cell biology has emerged as a promising field in reproductive medicine due to the unique capacity of stem cells for self-renewal and differentiation into specialised cell types, including germ cells and reproductive tissues. A critical determinant of stem cell fate is the intricate network of signaling pathways that regulate survival, proliferation, and lineage commitment. Understanding how these signaling cascades function in the reproductive context provides valuable insights into the pathophysiology of infertility and potential regenerative therapies.
Several canonical signaling pathways are essential for stem cell regulation in reproductive systems. The WNT/β-catenin pathway controls germ cell specification, folliculogenesis, and testicular development. Dysregulation of WNT activity has been associated with impaired spermatogenesis and ovarian dysfunction. The Notch pathway is involved in cell–cell communication within the ovarian niche, influencing granulosa cell proliferation and oocyte maturation. Notch signaling contributes to the maintenance of spermatogonial stem cells in the testis. The PI3K/AKT/mTOR pathway is a central regulator of cellular metabolism, growth, and survival, and plays a decisive role in follicle activation and ovarian reserve maintenance. Aberrant PI3K/AKT signaling can lead to premature ovarian failure or subfertility. Similarly, the TGF-β/Smad pathway orchestrates communication between somatic and germ cells, regulating follicle growth, Sertoli cell function, and overall gonadal homeostasis. Additional pathways, including Hedgehog and Hippo-YAP/TAZ, modulate stem cell differentiation and organ regeneration within reproductive tissues.
Beyond their biological role, stem cell–based models have revolutionised the study of infertility mechanisms. The derivation of gamete-like cells from pluripotent stem cells and the development of ovarian and testicular organoids provide powerful in vitro systems to dissect disease pathways, identify therapeutic targets, and test novel drugs. These advances hold promise for patients with conditions such as premature ovarian insufficiency, non-obstructive azoospermia, or chemotherapy-induced gonadal damage, where conventional ART is ineffective.
From a therapeutic standpoint, stem cell–based interventions aim to restore or replace defective reproductive cells and tissues. Mesenchymal stem cells (MSCs) have been shown to improve ovarian function by paracrine secretion of growth factors and anti-inflammatory molecules. Induced pluripotent stem cells (iPSCs) can be directed toward germline differentiation, offering a personalised source of gametes. Experimental transplantation of stem–derived cells or bioengineered grafts has demonstrated potential to rescue fertility in animal models. However, significant challenges remain, including the risk of tumorigenesis, incomplete functional maturation of stem cell–derived gametes, and unresolved ethical and regulatory issues.
Future integration of stem cell research with cutting-edge technologies such as CRISPR-Cas9 genome editing, single-cell transcriptomics, and bioengineered 3D culture systems will accelerate progress toward clinical translation. Personalised reproductive medicine, where patient-specific stem cells are used to generate functional gametes or restore gonadal tissue, may become a reality soon.
Methods: This review summarises findings from recent studies retrieved from PubMed and Scopus using keywords related to stem cells, infertility, and signalling pathways.
Results: Evidence shows that pathways such as WNT, Notch, PI3K/AKT, and TGF-β regulate stem cell fate in reproductive tissues. Stem cell–based models and therapies demonstrate potential to restore fertility, though safety and ethical challenges persist.
Conclusion: In conclusion, stem cell signaling is fundamental in regulating reproductive biology and infertility treatment. By elucidating the molecular mechanisms that govern stem cell fate decisions, researchers can harness this knowledge to develop innovative therapeutic strategies. While significant hurdles remain, the convergence of stem cell biology, molecular signaling, and reproductive medicine offers unprecedented opportunities for addressing one of the most pressing challenges in human health: infertility.