Establishment of Endometriotic Models: The Past and Future

Endometriosis affects 6–10% of reproductive-age women—yet after over a century of research, its root causes and best treatments remain poorly understood. For scientists, solving this mystery depends on experimental models: tools that mimic the disease in the lab (in vitro) or in animals (in vivo). These models help unlock how endometriosis develops, why it causes pain and infertility, and which therapies might work.

In a 2020 review published in the Chinese Medical Journal, researchers from Peking Union Medical College Hospital (Beijing) summarized the most common endometriosis models—from cell lines to cutting-edge “organoids”—and explained how they’re shaping the future of research.

Why Models Matter

Endometriosis occurs when uterine lining cells (endometrium) grow outside the uterus, usually in the pelvis. The disease is estrogen-dependent, inflammatory, and often invasive—but why some women get it (and others don’t) is still unclear. Models let scientists:

Study how endometriosis cells attach to and invade tissues
Test new drugs without risking patient safety
Explore genetic and hormonal drivers of the disease

In Vitro Models: Cells and Organoids in the Lab

In vitro (Latin for “in glass”) models use cells or tissues grown in the lab. They’re cheap, easy to manipulate, and ideal for studying basic biology.

1. Primary Cells and Immortalized Cell Lines

Primary cells are taken directly from endometriosis lesions (e.g., ovarian cysts or peritoneal implants). They’re great for capturing the disease’s true characteristics—but they die quickly in the lab. To fix this, scientists create immortalized cell lines: cells modified with viruses (like SV40 T antigen) or genes (like hTERT, which maintains telomeres) to keep dividing indefinitely.

Key cell lines include:

EEC12Z: A widely used line from peritoneal endometriosis. It’s invasive, lacks the “sticky” protein E-cadherin (which normally keeps cells in place), and responds to hormones.
EMosis-CC/TERT1: An immortalized line from ovarian endometriomas (cysts). It’s used to study how endometriosis might turn into ovarian cancer.

These lines are workhorses—but they have limits. Over time, they can lose key traits (like hormone receptors) or develop genetic changes that make them less like real endometriosis.

2. Stem Cells: The “Seed” of Endometriosis?

More than 90% of women have retrograde menstruation (menstrual blood flowing backward into the pelvis)—but only 6–10% get endometriosis. Scientists think endometrial stem cells are the missing link. These rare cells can renew themselves and form new tissue. When they’re shed during menstruation, they might implant in the pelvis and grow into endometriosis lesions.

Studies show stem cells from endometriosis patients are more invasive and better at forming blood vessels than normal stem cells. Drugs like sorafenib (used for cancer) might block these traits—offering a non-hormonal treatment option.

3. Organoids: Tiny Tissues That Mimic the Real Thing

The biggest breakthrough in endometriosis modeling is endometrial organoids—3D clusters of cells that grow into mini versions of the endometrium in a dish. Unlike flat cell lines, organoids:

Have the same structure as real endometrium (with glands and stroma)
Respond to hormones (e.g., estrogen makes them grow, progesterone makes them “decidualize” like the uterine lining during pregnancy)
Keep the genetic “fingerprint” of the original tissue (even after months of growth)

This is huge for personalized medicine. For example, organoids from a patient with severe endometriosis can be used to test which drugs shrink lesions—no more guessing if a treatment will work. They also solve a major flaw of cell lines: over time, cell lines lose genetic diversity, but organoids stay true to the original tissue.

In Vivo Models: Animals That Mimic Endometriosis

In vivo (Latin for “in living”) models use animals to study endometriosis in a whole-body context. They’re essential for testing how treatments affect fertility, pain, and inflammation.

1. Non-Human Primates (NHPs): Baboons as “Human Surrogates”

Baboons are the gold standard for endometriosis research—they get the disease naturally, have menstrual cycles, and their lesions look just like humans’. Scientists can even induce endometriosis by injecting menstrual blood into their pelvises (mimicking retrograde menstruation).

But NHPs have big downsides: they’re expensive, require specialized facilities, and raise ethical concerns. Most labs can’t afford to use them regularly.

2. Rodents: Rats and Mice for Fast, Cheap Research

Rats and mice are the workhorses of endometriosis research. They’re cheap, easy to breed, and can be genetically modified (e.g., knockout mice missing a gene linked to endometriosis).

To induce endometriosis, scientists surgically attach pieces of the uterus to the peritoneum (the lining of the abdomen). This mimics how lesions form in humans. Rodent models are great for studying:

How inflammation and angiogenesis (blood vessel growth) drive endometriosis
New drugs (e.g., cisplatin or letrozole)

But rodents don’t have periods, and their immune systems are different from humans. Results from mice don’t always translate to people—for example, a drug called IFN-α-2b works in rats but makes endometriosis worse in patients.

The Future: Organoids Lead the Way

Older models have served science well, but they have critical flaws:

Cell lines lose genetic traits over time.
Animal models aren’t human—results can be misleading.
Primary cells don’t live long enough for long-term studies.

Organoids fix almost all these problems. They’re:

Genetically stable: Keep the original tissue’s DNA.
Human-relevant: Mimic the structure and function of real endometrium.
Personalized: A patient’s own organoids can be used to test drugs.

Scientists are already using organoids to study:

Why some endometriosis lesions are more invasive
How hormones like estrogen drive the disease
Patient-specific responses to therapies (e.g., dienogest, a progestin used to treat endometriosis)

Conclusion

Endometriosis is a complex, heterogeneous disease—but models are helping scientists crack its code. From immortalized cell lines to baboon models, each tool has taught us something new. But organoids are the future. They’re the closest thing we have to studying endometriosis in a dish—and they could revolutionize personalized medicine for millions of women.

As the review’s authors write: “Different models complement each other to advance endometriosis research. The successful establishment of endometrial organoids means they are expected to become an ideal model for studying endometriosis in the future.”

This review was led by Zhi-Yue Gu, Shuang-Zheng Jia, and Jin-Hua Leng from the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.

Original study: Gu ZY, Jia SZ, Leng JH. Establishment of endometriotic models: the past and future. Chin Med J 2020;133:1703–1710. doi:10.1097/CM9.0000000000000885

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