How Does Endometriosis Develop?

Endometriosis Guest Series with Katie Edmonds

Part One: What is Endometriosis?

Part Two: How Does Endometriosis Develop?

Part Three: Endometriosis and Immune Dysfunction

Part Four: Understanding & Managing Endometriosis Symptoms

Part Five: 3 Short Videos on Endometriosis That Will Blow Your Mind

This month on the blog, we have a 5-part endometriosis series by guest expert Katie Edmonds. Last week, Katie answered the question, “What is endometriosis, really?”. In this post, she’ll explain how endometriosis develops in the body.

How Does Endometriosis Develop?

Endometriosis takes many steps to form into the fully established disease we know. No, you didn’t just “catch endo” like the flu, even if it felt like symptoms came on fast and hard. There are so many steps in developing endo that it’s much more like a story unfolding, and a BIG story at that. Still, this story has a clear beginning: The creation of an endometriosis-like (endo-like) cell. These cells are similar to the cells of the endometrial lining, but distinctly different… and not in a good way.

Endo-like cells are more like jacked Navy SEALs than cushions of fertility. They are often highly sensitive to estrogen and very resistant to progesterone, meaning there’s lots of growth without much cooling. They can avoid normal cellular death and immune cleanup processes, and become pain factories. These cells are great at migrating, self-healing, and invading into the smallest nooks and crannies (which may be associated with the start of adenomyosis in the uterine wall)(1). Where did this thing come from? Turns out, research has ‘a great many ideas.

Meet Your Endometrial Cells

Endometrial cells line the inside of the uterus, making up your endometrial lining, or endometrium. This lining grows each month in preparation for a baby to be implanted, and, if no baby comes, shed with menses. After shedding, this tissue regrows! We don’t give it enough credit for doing this. Like, wouldn’t it be great if fingers re-grew if they were cut off? They don’t, but your endometrial cells do. This is thanks to the stem cells within that allow your normal endometrial cells to have this superpower. In fact, for the sake of this endo story, we could think of these cells as superheroes.

Side note: understanding how those endo cells got to where your lesions are is a whole other can of worms. For now, know that yes, it’s totally possible for endometrial cells to be born a hop, skip, and a jump outside of the uterus, in something called Müllerian rests. Not a problem in healthy individuals…. although obviously a problem if those cells start behaving like endo.

Training Endometrial Cell Superheroes To Become Supervillains

In the case of endo, it appears some of these endometrial cells are behaving quite differently. How?

Genetically, you inherit a mixed bag of cellular behaviors, some of which will be stuck with you for life. But, here’s a pop quiz: If corn has 32,000 genes and a tree has 45,000, how many genes do humans have? Only about 25,000!  Fewer than corn.

It’s possible for humans have less genes than corn (or trees, for that matter) thanks to epigenetics. Epigenetics is how genes can change their behavior depending on what “information” they pick up. In fact, gene behaviors can turn “on” or “off” based on any number of lifestyle experiences you have throughout your entire life, including stress levels, diet, sun exposure, community level, toxins, and more! This is how a measly 25,000 genes can change their behavior so profoundly from person to person, allowing us to have fewer genes yet be so complex. These epigenetic changes can also be beneficial, or not… mostly the latter when it comes to endometriosis.

Research has pinpointed numerous genetic and epigenetic alterations that create a supervillain out of your superhero endometrial cell, becoming the highly feared endo-like cell. Dun, dun, dunnnn. Here are examples of some contributors:

GENETICS: SHAKE WHAT YOUR MAMA GAVE YOU

To start, it’s estimated that a little over half of us (51% of us, to be exact) may be born with the genes that predispose us to develop endo. For example, a protein-coding gene called BCL6 may set our endometrial cells up for progesterone resistance. Another gene (NPSR1) may contribute to some of the pain and inflammation we face. Gene inheritance is how endo can run in families, as in, your more likely to develop endo if your mother had it.

But, even though you have have inherited “endo genes”, it doesn’t mean your normal endometrial cells will automatically become supervillains, just that you have a lot more likelihood of it happening. You also can develop endo even if it doesn’t run in your family. This is how genetics is one factor of many in “getting endo”, but it’s not a genetic disease. (2-4)

EPIGENETICS AND DIOXINS

Dioxins are one of the most feared environmental contaminants worldwide. They are nasty byproducts of industrial and farming processes that linger in the environment for decades, known to be potent endocrine disruptors and linked to a variety of diseases, including endometriosis.

Endometrial cells exposed to dioxins can get their behavior scrambled, so-to-speak, in ways that prevent normal cell death—something you really want when it comes to endo. Dioxins can also contribute to progesterone resistance and create abnormalities with the Homeobox A10 gene, which effects fertility. And, because the epigenetic effects of dioxins are so potent, there is concern that these can be passed down inter-generationally (meaning you could have inherited these epigenetic changes from your mother or grandmother who was exposed, even if you yourself weren’t). (5-6)

EPIGENETICS AND PHTHALATES

Phthalates are used to make plastics durable and fragrances last longer, they’re found in everything from synthetic floor tiles and carpets to lipstick, and your favorite smelling shampoo, body wash, and perfume. Yes, even if organic or “all natural” (because of a loophole, if you see fragrance/parfum as an ingredient it almost certainly has phthalates in it). 

When normal endometrial cells are exposed to phthalates they not only show signs of inflammation and oxidative stress, but they also become more invasive and proliferative, much like the behavior of an endo-like cell.

Unfortunately, there are 13 different studies demonstrating those with endometriosis have higher levels of phthalates in their blood, urine, or peritoneal fluid  (the slippery, immune rich liquid that lines your peritoneal cavity) than those without endo. We’re smothered, and our endometrial cells may be paying a high price. (7-8)

EPIGENETICS AND BPA, AND HER EVIL FRIENDS BPS, BPAF, AND MORE

Bisphenol A, commonly called BPA, is used primarily to make plastic products, as well as acting as protective coating for things like food and drink cans, hot coffee cups, and thermal receipt paper. Itʻs basically everywhere. Exposing normal endometrial cells to BPA has been shown to significantly decrease progesterone receptors, creating an estrogen-dominant endometrial cell that is apt to grow, grow, grow, without any cooling. (9-11)

EPIGENETICS AND CHRONIC INFLAMMATION

This part is fascinating (and one more way endometriosis is, at it’s root, an inflammatory condition)! If an innocent ‘ol endometrial cell is exposed to inflammation for too long, it can start to behave more like endo. The way this happens is actually through a side effect of chronic inflammation: the suffocation of your cells. This is called hypoxia. Without oxygen your cells cannot function—as you know, if you’ve ever had a leg fall asleep from sitting the wrong way. 

Why would your endometrial cells be suffocating? There are numerous facets linked to endo I’ll discuss in following blogs, including bacterial overgrowths in the reproductive tract or gut (both biggies for creating chronic inflammation with endo!), chemical exposure, excess blood in the peritoneal cavity (from too heavy menses combined with retrograde flow, or established endo lesions once they take hold), lack of anti-oxidants, sedentarism, and more. Once endo is established, it will also contribute to the equation. 

When chronic inflammation ensues, it damages our cellular ability to get oxygen. To survive this suffocation, our normal endometrial cells have a last-ditch epigenetic survival tactic: turning into a mesenchymal cell, a type of stem cell that has even more superpowers than usual. Unfortunately, with power comes supervillain attitude, and these new endometrial mesenchymal cells may start to adopt even more endo-like behaviors: increased invasiveness into small nooks and crannies, an enhanced ability to migrate around the body, and even more resistance to cellular death. 

This is why chronic inflammation may be another prerequisite for the early development of an aggressive endo-like cell. (12-13)

Creating Different Types of Endo

The unique combination of:

1. the genes we were born with, plus

2. the epigenetic behaviors they accrue over time

are the main reason why we develop an endo-like supervillain in the first place. These very different combinations also explain how there can be so many different types of endo—perhaps up to 65 different types! Really? Yes.

These different types have different behaviors, for example:

• While most types of endometriosis regress during pregnancy, other can progress.

• Some types of endometriosis grow slowly and may barely spread, while others grow and spread at a rapid rate.

• Certain types of deep endometriosis lesions are associated with cancer, while others are not.

• There are a wide variety of inflammation levels around what appear to be similar types of lesions, meaning that the immune reaction is widely diverse among types.

• Progesterone resistance in endo types vary from non-existent to very pronounced.

• While most endo requires estrogens to grow, some can develop without much estrogen, as seen in men or women more than 10 years after menopause (who aren’t taking hormones).

The wide variety of differing behaviors also helps us understand how endo effects our bodies differently! For example, why there’s such a wide array of symptoms experienced by endo sufferers, why different treatment options work well for some people and not at all for others, and why we benefit from unique treatment plans rather than the same blanket treatment strategy for all types. (14-15)

Retraining the Supervillain

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Guest Expert: Katie Edmonds

 

 

 

Katie Edmonds is a Nutritional Therapist, Paleo Autoimmune Certified Coach, creator of the popular blog Heal Endo, and author of the 4-Week Endometriosis Diet Plan and Heal Endo: An Anti-inflammatory Approach to Healing from Endometriosis.

After putting her own endometriosis into remission, something she never knew was possible, Katie has developed education and offerings around a research-backed diet and lifestyle shown to help heal the chronic inflammation and immune dysfunction that those with endometriosis experience.

Through her books and blog, her work has impacted the lives of tens of thousands by informing a new way forward when living with a chronic disease like endo. Katie doesn’t believe getting an endo diagnosis should be the beginning of the end and believes there is truly a much better way to approach endometriosis, both in the doctor's office and at home.

 

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