More Than Just a "Nurse Cell": 150 Years of Discovery and Allure
In the intricate symphony of human reproduction, one cellular conductor has been quietly directing the process for 150 years. Discovered in 1865 by the Italian physiologist Enrico Sertoli, the Sertoli cell was initially described as a "tree-like" or "stringy cell" within the testis 1 8 . Sertoli himself presciently referred to it as a "mother cell," hinting at its nurturing role 1 .
Enrico Sertoli first describes the "tree-like" cells in the testis
Microscopists study the cell's structure in detail
Molecular functions and secretions are identified
Plasticity and therapeutic potential are explored
For decades, Sertoli cells were a subject of study primarily for microscopists, a beautiful but enigmatic structure. Today, we recognize them as one of the most versatile and dynamic cells in the body—a master of structure, nutrition, immune defense, and metabolic control, all essential for creating new life.
Fun Fact: Each Sertoli cell can support up to 40 germ cells at different stages of development simultaneously!
Sertoli cells are tall, columnar cells that stand like ancient pillars within the microscopic, coiled seminiferous tubules of the testes 5 . Their primary mission is to nurture and support the development of sperm, from their earliest beginnings as spermatogonia to their final release as mature spermatozoa 1 5 .
The most critical architectural feat of Sertoli cells is the construction of the blood-testis barrier (BTB) 1 5 . This specialized structure is formed by tight junctions between adjacent Sertoli cells, effectively dividing the tubule into two compartments:
The BTB is not just a simple wall; it is a sophisticated checkpoint that performs two vital functions:
Beyond their structural role, Sertoli cells are biochemical powerhouses, secreting a plethora of substances essential for spermatogenesis 1 :
| Secretion | Primary Function | Importance Level |
|---|---|---|
| Androgen-Binding Protein (ABP) | Concentrates testosterone in seminiferous tubules to stimulate spermatogenesis 1 5 . |
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| Anti-Müllerian Hormone (AMH) | Prevents development of female reproductive structures in male fetuses 1 5 . |
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| Inhibin B | Provides negative feedback to the pituitary gland to regulate FSH secretion 5 . |
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| Lactate | Serves as the main energy source for developing germ cells 4 . |
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| Transferrin | Delivers iron to developing germ cells 1 . |
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Sertoli cells are the main energy suppliers for developing sperm, converting glucose to lactate, which spermatocytes and spermatids use as their primary fuel 4 .
They also convert testosterone to estradiol, directing the process of spermatogenesis 1 .
Sertoli cells contain the enzyme aromatase that facilitates this conversion
The "plasticity" of the Sertoli cell is marvelously evident when comparing different branches of the animal kingdom.
In mammals, Sertoli cells were long thought to be terminally differentiated after puberty, meaning they could no longer divide 1 8 . The total number of Sertoli cells set at puberty was believed to determine the ultimate sperm production capacity of the adult .
Recent Discovery: Under certain conditions, such as after transplantation, these cells can regain the ability to proliferate 1 .
In fish and amphibians, Sertoli cells retain a remarkable ability to proliferate throughout life in two distinct phases:
This demonstrates an evolutionary plasticity, where the same core cell type has adapted different strategies across species to accomplish the same ultimate goal: producing viable sperm.
As air pollution became a major 21st-century public health challenge, scientists noticed a disturbing trend: a global decline in sperm quality. A key question emerged: could PM2.5—the fine particulate matter small enough to penetrate the body's protective barriers—be a culprit? The suspicion fell on the Sertoli cell, the guardian of the sperm production environment.
| Parameter Investigated | Observation with PM2.5 Exposure | Effect of NQO1 Overexpression |
|---|---|---|
| Mitochondrial Structure | Severe damage; cristae disintegration 2 | Not directly measured, but function improved |
| Reactive Oxygen Species (ROS) | Increased by 1.8-fold 2 | Increased SOD activity (+35%), reduced oxidative damage 2 |
| UPRmt Pathway Activity | Activated in a concentration-dependent manner 2 | Increased UPRmt protein levels by 40-60% 2 |
| Cell Survival (Bcl-2/Bax Ratio) | Decreased (inferred) | Increased by 2.1-fold 2 |
| Cell Death (Apoptosis) | Significantly induced | Significantly suppressed 2 |
The story of the Sertoli cell doesn't end with sperm production. Its unique ability to create an immune-privileged site has inspired scientists to explore its use in cell therapy 1 .
In experimental models of Type I diabetes, researchers have co-transplanted insulin-producing β cells together with Sertoli cells into recipient organisms 1 . The Sertoli cells act as biological bodyguards, protecting the β cells from immune rejection without the need for powerful immunosuppressive drugs, successfully restoring glucose homeostasis in mice, rats, and humans in these studies 1 .
Mice
Rats
Humans
A 2025 study identified a long non-coding RNA called LINC00467 that regulates a specific type of Sertoli cell death known as ferroptosis in men with non-obstructive azoospermia (NOA) 6 .
This opens up another new pathway for potential therapeutic intervention for male infertility.
From its elegant structure first glimpsed under a simple microscope 150 years ago to its newly discovered roles in responding to modern environmental threats, the Sertoli cell has proven to be a cell of remarkable beauty and plasticity. It is far more than a passive "nurse"; it is an active director, a steadfast guardian, and a versatile partner in the miracle of life.
As we continue to unravel its secrets, the Sertoli cell not only promises new hope for treating infertility but also serves as a model for innovative therapies in regenerative medicine, proving that this timeless cell is perfectly poised for the future.