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Induction of menstruation in mice reveals the regulation of menstrual shedding

Reposted by Çağrı Çevrim

Hannah Haberkern @hannah-haberkern.bsky.social · 12h

Amazing! Hard to believe this didn't exist until now.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

I’m thrilled to share my postdoc work and the first paper from the McKinley Lab! 🎉
@karalmckinley.bsky.social
We built the first transgenic model of menstruation in mice.
We used it to uncover how the endometrium organizes and sheds during menstruation. 🧪
www.biorxiv.org/content/10.1...
🧵

During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this co...

www.biorxiv.org

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Reposted by Çağrı Çevrim

@NicoliLab @nicolilab.bsky.social · 18h

OMG 😱 a true game changer for biology! Menstruation is a natural miracle of tissue regeneration. Amazing biology to come!

Çağrı Çevrim @cagricevrim.bsky.social · 19h

I’m thrilled to share my postdoc work and the first paper from the McKinley Lab! 🎉
@karalmckinley.bsky.social
We built the first transgenic model of menstruation in mice.
We used it to uncover how the endometrium organizes and sheds during menstruation. 🧪
www.biorxiv.org/content/10.1...
🧵

Induction of menstruation in mice reveals the regulation of menstrual shedding

During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this co...

www.biorxiv.org

1 4 12

Reposted by Çağrı Çevrim

Adam Gracz @graczlab.bsky.social · 16h

This is probably one of the coolest and most creative mouse models I’ve ever seen!

Kara McKinley @karalmckinley.bsky.social · 18h

Lab’s 1st preprint!

Menstruation is understudied due to societal taboos + a biological challenge: mice (a key system for research + drug discovery) don’t menstruate.

@cagricevrim.bsky.social made menstruating mice + used them to discover early events in menstruation.

He is on the job market!

Çağrı Çevrim @cagricevrim.bsky.social · 19h

I’m thrilled to share my postdoc work and the first paper from the McKinley Lab! 🎉
@karalmckinley.bsky.social
We built the first transgenic model of menstruation in mice.
We used it to uncover how the endometrium organizes and sheds during menstruation. 🧪
www.biorxiv.org/content/10.1...
🧵

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Çağrı Çevrim @cagricevrim.bsky.social · 17h

Thank you for your kind words ❤️ Coming from someone who works with Hofstenia, that means a lot!

Çağrı Çevrim @cagricevrim.bsky.social · 17h

Thank you!
It’s nice to see other people sharing our excitement!

Çağrı Çevrim @cagricevrim.bsky.social · 18h

Thanks Anna! ❤️

Çağrı Çevrim @cagricevrim.bsky.social · 19h

Thank you!

Çağrı Çevrim @cagricevrim.bsky.social · 19h

Last but not least, a huge thanks to all co-authors and collaborators.
This was truly a team effort that brought together many people with different expertise.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

In short, we developed the first transgenic menstruating mouse and discovered a new principle of endometrial layering and regeneration.
X-Mens opens the door to studying menstrual biology and pathologies with precision and help closing the longstanding gap in women’s health research.

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Çağrı Çevrim @cagricevrim.bsky.social · 19h

So the entire endometrium is organized radially, from undifferentiated fibroblasts to the most mature decidual cells.

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Çağrı Çevrim @cagricevrim.bsky.social · 19h

These rings form a gradient. Young decidual cells sit at the edge, mature ones at the center. As the gradient expands, it pushes undifferentiated fibroblasts to the periphery, creating the basalis, and defining the plane of shedding.

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Çağrı Çevrim @cagricevrim.bsky.social · 19h

Next, we built a fine time-series of X-Mens cycles to see how these layers form.
To our surprise, the functionalis is not a single layer.
It has three concentric rings of decidual cells, each at a different stage of differentiation.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

And our comparative analysis showed that the functionalis and basalis layers in X-Mens mice and humans are highly similar.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

We used Slide-tags, a spatial single-cell RNA sequencing method, to map this layering in detail using both human and X-Mens uterine samples.

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Çağrı Çevrim @cagricevrim.bsky.social · 19h

We next took a century old challenge.
The human endometrium has been known to have two layers:
the functionalis, which decidualizes and sheds, and the basalis, which stays intact and regenerates the tissue.
The amazing part?
X-Mens mice show the same architecture.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

X-Mens menstruation recapitulates key aspects of human menstruation.
Single-cell analyses showed shared genetic programs between the two species.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

Inducing decidualization in non-pregnant mice causes endometrial shedding and vaginal bleeding, just like in humans when progesterone levels fall.
So, our transgenic system enables repeatable induction of menstruation in mice.
We call it X-Mens!

Çağrı Çevrim @cagricevrim.bsky.social · 19h

We used chemogenetics to trigger decidualization, a key transformation in the uterine lining (endometrium) that happens cyclically in humans but only during pregnancy in mice.

Çağrı Çevrim @cagricevrim.bsky.social · 19h

First things first: yes, mice do not naturally menstruate.
In fact, fewer than 2% of mammals do, and none of them are standard lab animals.
This scarcity made studying menstruation extremely difficult for decades.