Thank you so much 😄 It was a joy putting it together!

Absolutely! Anytime I thought the uterus would pick option A or B, it would proceed to pick option ₩§°ž»

…and I love that!

1st McKinley Lab grad student’s 1st preprint!
@claireang.bsky.social studied how the uterus safely excises massive amounts of tissue during menstruation and pregnancy.

Come for her GORGEOUS images, stay for her incredible discoveries.
www.biorxiv.org/content/10.6...
w/ @akelleher1017.bsky.social

Thank you so much!! It’s such an incredible system. Never fails to amaze me!!

Thanks!! 😄

Thank you so much!!

Bonus shoutout to @akelleher1017.bsky.social for making a *reliable* Cre line, and to biology, for coming up with such beautiful solutions to complex problems!

This project was a wild ride, and I’m thankful to have been on it with @karalmckinley.bsky.social and such incredible lab mates and collaborators! Thank you all!

Top: Schematic of mouse uterus at homeostasis showing magnified cross-section with intact green luminal epithelium and blue glands. Bottom left (blue box, chemical ablation pathway): mid-point shows complete epithelial depletion with glands remaining, and the recovered timepoint shows dark blue luminal epithelium re-epithelialized from glandular progenitors. Bottom right (green box, menstruation and pregnancy pathways): pregnancy mid-point shows gold central tissue, which will eventually shed, with an intact green luminal epithelial smile and blue glands. The menstruation mid-point shows gold shedding tissue with smile-shaped green epithelial structures. Recovered timepoints for both pregnancy and menstruation show restored green luminal epithelium from luminal progenitors. Labels indicate glandular versus luminal progenitor sources.

Instead, epithelial remodeling during menstruation and pregnancy bypassed the need for gland contributions by covering stromal tissues before injury.

In short:

We looked in young mice.
We looked in aged mice.
We looked after inducing menstruation.
We looked during pregnancy.
We looked after childbirth.
We even looked in one case of natural miscarriage.

Aaand gland contributions were minimal in all cases except luminal epithelium ablation.

As for humans, we can’t say for sure what’s happening there. There is evidence that the glands contribute to epithelial regeneration in the human endometrium, but the role of luminal epithelium has remained underexplored.

Two historical pen-and-ink anatomical drawings from Van Der Horst (1954) showing uterine cross-sections from young (left) and aged (right) elephant shrews during menstruation. Both drawings depict gland structures throughout the tissue, and epithelial sheets extending around the periphery of a central mass of tissue, reminiscent of the smile structures. Citation: C. J. Van Der Horst; Elephantulus going into anoestrus; menstruation and abortion. Philos Trans R Soc Lond B Biol Sci 10 December 1954.

These mechanisms may not be limited to just lab mice. Naturally menstruating spiny mice lack glands entirely, and drawings of menstruating elephant shrew endometrium from 1954 exhibit structures remarkably similar to smiles.

The coolest thing about this mechanism is that it can minimize the exposure of stromal tissues, which are sensitive and prone to scarring if they’re not re-epithelialized quickly. It’s like the endometrium is repairing itself before the damage even occurs.

Schematic showing the orientation of a longitudinal section of a pregnant mouse uterus with multiple implantation sites (pink beads). Bottom: Immunofluorescence image of a longitudinal cross-section collected on day 7.5 of pregnancy, showing cyan smile-shaped structures (white dashed outlines) flanking each central implantation site (green). Scale bar 500 μm.

And when we looked at linage tracing results from mid-pregnancy, we found similar smile structures enveloping each implantation site. Like menstruation, the glands only made minor contributions to the smiles.

Occlusion and reformation of the rat uterine lumen during pregnancy Implantation sites were obtained from rats at various stages of pregnancy and were studied by light microscopy and scanning electron microscopy. Early in pregnancy the uterine luminal epithelium and ...

Then I had a lightbulb moment 💡 These structures reminded me of the process of epithelial remodeling that occurs in rat pregnancy, which Welsh and Enders described over 40 years ago. onlinelibrary.wiley.com/doi/abs/10.1...

Three immunofluorescence cross-sectional images showing variability during the first day of menstruation. Cyan smile-shaped epithelial structures (outlined with white dashed lines) wrap increasingly around the central yellow shedding tissue. Images are arranged from left to right, with gradually increasing degrees of shedding tissue envelopment. Top row shows emoji faces with a neutral smile, wider smile, and a highly curved smile to indicate smile shape progression. Scale bar 500 μm.

Cyclic schematic of four uterine cross-sections, showing the stages of re-epithelialization during menstruation. Starting from top: (1) intact uterus with green luminal epithelium and blue glands → (2) differentiation/formation of shedding tissue (gold) at the center of the tissue. The luminal epithelium has been pushed to the periphery of the shedding tissue → (3) peripheral luminal epithelium (the smile) has widened along the border of the shedding tissue (gold dashed line) → (4) the luminal epithelium smile has enveloped the whole mass of tissue in the center, which then sheds. Retained tissue is also lined with luminal epithelium. → (1) the luminal epithelium folds back down to its normal shape to return the tissue to its original intact state. The luminal epithelium remains green.

So where did all the luminal epithelium come from, if not from the glands? On day 1 of menstruation, we found luminal epithelium wrapping around the shedding tissue in arched structures we called “smiles.” Surprisingly, smiles also covered the retained portions of the endometrium before shedding.

Side-by-side immunofluorescence microscopy images comparing uterine cross-sections with (right) or without (left) menstruation. Cyan luminal epithelium and yellow glandular structures embedded in magenta stromal tissue are visible in both images. Neither image contains yellow gland derived luminal epithelium. Scale bar 200 μm.

But what do the glands contribute during events that are a normal part of uterine biology, like menstruation?

Turns out, not a lot. After recovery from menstruation, <1% of the luminal epithelium had come from the glands, which was the opposite of what we expected.

Top: Schematic of Cxcl15iCre R26nTnG mouse model showing Cre- cells marked with Tomato (magenta) and Cre+ or descendant cells marked with GFP (yellow). Bottom: Side-by-side immunofluorescence microscopy images. Left (-ablation): gland lineage in yellow makes only minor contributions to the luminal epithelium. Right (recovered from ablation): an intact yellow luminal epithelium indicates re-epithelialization from gland lineages.

Three-panel uterine cross-section diagram showing progression through luminal epithelium ablation and recovery: (1) homeostatic tissue with intact green luminal epithelium and blue glands → (2) Ablated tissue with luminal epithelium removed, only glands remain → (3) Regenerated tissue with luminal epithelium (now blue) fully restored, demonstrating complete re-epithelialization capacity.

Lo and behold, the glands re-epithelialized the entire lumen within 72h of ablation! And this epithelium was functional—it could support pregnancy. 9/12 mice that underwent ablation carried litters to term, compared to 7/12 unablated controls.

Side-by-side immunofluorescence microscopy images. Left (-ablation): intact luminal epithelium in cyan lines the lumen in the center of the tissue. Glands in magenta bud off the luminal epithelium. Right (+ablation): glands remain intact, but the luminal epithelium has been depleted. Scale bar 200 μm.

Lineage tracing in mice revealed that glands only minimally contribute to luminal epithelium in uninjured endometrium, so we chemically ablated the luminal epithelium to see if the glands could regenerate it.

Schematic of mouse uterus showing cross-sectional anatomy. Pink tube-shaped structure labeled "mouse uterus" with a magnified cross-section with green luminal epithelium bordering the lumen. Blue glands branch off the luminal epithelium. Further magnification of one gland structure details endometrial layers: green luminal epithelium at the top (bordering the lumen) and blue glandular structures (CXCL15+) embedded in pink stromal tissue.

Circular diagram illustrating conventional model of menstruation. Four stages connected by arrows: (1) uninjured endometrium with intact luminal epithelium (green) and a gland (blue) → (2) tissue shedding where upper portion of tissue, including luminal epithelium and upper stroma, are lost → (3) new luminal epithelium emerges from exposed glands → (4) full restoration of the luminal epithelium → (1) return to intact tissue.

The conventional model of menstruation is that chunks of superficial endometrium are shed, which uncovers underlying gland structures that go on to provide new epithelial cells to restore the luminal epithelium.

When I started, I wanted to know how the uterine epithelium regenerates across menstruation, pregnancy, and childbirth, which all involve significant disruption to the endometrial tissue lining the uterine cavity.

Excited to share my new preprint from the McKinley lab, where we explored regenerative mechanisms across menstruation and pregnancy! We thought specialized glands would regenerate everything.

We were wrong.

But the real mechanism turned out to be way cooler :) 🧪🧵
www.biorxiv.org/content/10.6...

Lab mice can now have periods like humans Studies of rodents with a menstrual on/off switch could help people with endometriosis and other disorders

Thrilled to see our preprint featured in Science News! 🩸

Big thanks to Holly Barker for writing such a thoughtful piece about our work. So exciting to see broader attention to menstruation research and new model systems!

www.science.org/content/arti...

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!

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...

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...
🧵

ReproBioArt 2025 #ReproBioArt: Where science becomes art. Explore incredible images from reproductive biology research and consider submitting your own to win free registration to SSR 2026! @SSRrepro

The 2025 edition of ⁦‪SSRepro‬⁩ #ReproBioArt image contest is live and the gallery is filling up with such beautiful images! Submit yours today!!
#ReproRocks ⁦

woobox.com/2poyka/galle...

Thank you Kara!! All the credit goes to you for building such a supportive lab environment and encouraging me to grow into leadership roles!

Honored to have received this mentorship award! Being nominated by my colleagues makes it especially meaningful and it’s been so enriching to have the opportunity to support and grow with so many incredible people!!

“women will control around two-thirds of all private wealth in the US by 2030,” via @semafor.com

www.mckinsey.com/~/media/McKi...