Abstract
The prostate is vulnerable to two major age-associated diseases, cancer and benign enlargement, which account for significant morbidity and mortality for men across the globe. Prostate cancer is the most common cancer reported in men, with over 1.2 million new cases diagnosed and 350,000 deaths recorded annually worldwide. Benign prostatic hyperplasia (BPH), characterised by the continuous enlargement of the adult prostate, symptomatically afflicts around 50% of men worldwide. A better understanding of the biological processes underpinning these diseases is needed to generate new treatment approaches. Developmental studies of the prostate have shed some light on the processes essential for prostate organogenesis, with many of these up- or downregulated genes expressions also observed in prostate cancer and/or BPH progression. These insights into human disease have been inferred through comparative biological studies relying primarily on rodent models. However, directly observing mechanisms of human prostate development has been more challenging due to limitations in accessing human foetal material. Induced pluripotent stem cells (iPSCs) could provide a suitable alternative as they can mimic embryonic cells, and iPSC-derived prostate organoids present a significant opportunity to study early human prostate developmental processes. In this review, we discuss the current understanding of prostate development and its relevance to prostate-associated diseases. Additionally, we detail the potential of iPSC-derived prostate organoids for studying human prostate development and disease.
Highlights
The prostate is a male reproductive accessory gland in the pelvis that secretes seminal fluid components
The expression levels of FOXA1 between male and female wallabies do not differ until branching morphogenesis and lumenisation, at which point expression drastically rises in males while remaining unchanged in females, indicating a sexual dimorphic expression change, in LNCaP cells, FOXA1 can bind to the enhancer regions of androgen receptor (AR)-regulated genes in the absence of androgens [88]
From the heatmap analysis we can observe the upregulation of key prostate development genes in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa), such as BMP4, HOXB13, FOXA1, and NKX3.1 In A we see increased expression of GLI1 and GLI2
Summary
The prostate is a male reproductive accessory gland in the pelvis that secretes seminal fluid components. The prostate of men clinically diagnosed with BPH usually increases from an average size of approximately 20 g, typical for a young adult around the age of 30, to a size of over 40 g in the following two decades This growth primarily involves the transitionalperiurethral zone (TPZ), which surrounds the urethra. Limited access to foetal prostate tissue has hindered further exploration of prostate development drivers and the theory of embryonic reawakening leading to prostate diseases in humans These limitations could be overcome by using human induced pluripotency stem cell (iPSC)-derived prostate organoids to study developmental processes in detail. We outline additional approaches to study prostate biology using iPSCs
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