Kate Cavanaugh

Happy Fluorescence Friday with this new preprint 👀

New job, new preprint! We found that embryo implantation can be understood as active wetting! Embryos from older mothers have trouble implanting because they are too contractile and viscous. Check out the wonderful thread (and movies!) by @katecavanaugh.bsky.social.

www.biorxiv.org/content/10.1...

Thank you!!! This was a fun paper to do/write. But Aren't we all just really really really old embryos anyway? 🤣😅

Thanks Vicky!! I hope you're doing well!

Thanks Rikki! I hope all is well with you! 💪

Thanks for the kind words, mark!!

Thanks Vinny! I hope you and yours are doing well!!!

Amazingly, yes! Here, we indexed embryos, calculated compaction metrics, and selected Normal and Accelerated tempo’d embryos for later implantation assays. We find compaction metrics correlate with ultimate implantation potential – for both aged and young maternal conditions.

Well, we also find increased contractility in the aged embryo also correlates with faster compaction at the 8-cell stage. Could this be a possible metric to see which ones will implant?

But contractility tunes cell-cell adhesion (limiting spreading) and cell-substrate adhesion (promoting spreading). Aged embryos show higher blastocyst surface tension AND higher spreading forces via Traction Force Microscopy. Weird… So how can we explain reduced spreading?

Using mouse embryos, we visualize implantation in vitro to see what’s wrong in embryo development w/ advanced maternal age. In vitro implantation assays show aged embryos do not implant as efficiently.

Thanks for following along. We hope this info can be used to improve IVF procedures to increase success rates for women of all ages. Please like/RT. @eshre.bsky.social #eshrejc @bwfund.bsky.social @hhmi.org #reproductivehealth #reproductivehealth #devbiol

We stand on the shoulders of giants! Many other groups have looked at compaction metrics - like the extent of embryo "flattening" as a way to show viability. But we hoped that we could fill the gap as to whether compaction itself correlates with later implantation potential 💪

we heavily used the Spirochrome dyes for this paper!

A mechanical origin for implantation defects in embryos from aged females https://www.biorxiv.org/content/10.1101/2025.09.29.679218v1

A profuse thank you to all collaborators - Diana Laird, @pwoakes.bsky.social , and @ricardalert.bsky.social – whose hard work really elevated our findings. Thank you to Orion, who gave me incredible freedom to explore this new research in the lab.

a close up of a person 's face with the words `` i want to be forever young '' . ALT: a close up of a person 's face with the words `` i want to be forever young '' .

And finally, can we rejuvenate embryos to restore developmental potential? We hope yes – by tuning embryonic contractility we may find the embryonic fountain of youth to improve fertility if this holds true for human embryos.

a little girl in a red dress is standing in front of a scale .. ALT: a little girl in a red dress is standing in front of a scale ..

What this also suggests is something out of Willy Wonka – we can use early compaction metrics to find the good and bad embryos. Talk about an Eggdicator…

To summarize - we find that there is an optimal contractile regime for embryos to undergo proper development/implantation. Contractility shifts the proportion of optimal embryos in each maternal condition.

Amazingly, yes! Here, we indexed embryos, calculated compaction metrics, and selected Normal and Accelerated tempo’d embryos for later implantation assays. We find compaction metrics correlate with ultimate implantation potential – for both aged and young maternal conditions.

Well, we also find increased contractility in the aged embryo also correlates with faster compaction at the 8-cell stage. Could this be a possible metric to see which ones will implant?

Egg Dfk GIF ALT: Egg Dfk GIF

So, seems like age-related implantation defects are driven by the egg/embryo itself! But how can we pick the good embryos that are competent to implant in IVF procedures? Can we leverage this mechanical info of implantation competence?

a black and white photo of a drop of water falling from a bottle on a concrete surface . ALT: a black and white photo of a drop of water falling from a bottle on a concrete surface .

Enter theory! We modeled embryos like a liquid droplet wetting on a surface. We find age-related spreading behaviors are explained by increased tissue viscosity, which limits implantation spreading. Imagine a droplet of water vs honey spreading…

But contractility tunes cell-cell adhesion (limiting spreading) and cell-substrate adhesion (promoting spreading). Aged embryos show higher blastocyst surface tension AND higher spreading forces via Traction Force Microscopy. Weird… So how can we explain reduced spreading?

Implantation is inherently a mechanical process. We find contractility is necessary and sufficient for spreading behaviors. We can artificially age embryos from young females and even rescue aged embryo spreading just by tuning contractility!

Using mouse embryos, we visualize implantation in vitro to see what’s wrong in embryo development w/ advanced maternal age. In vitro implantation assays show aged embryos do not implant as efficiently.

The “age” of an egg impacts its development. HFEA data on IVF uterine transfers shows live births = rescued if women >35 use donor embryos from women <35. We find this trend = true for aged mice, too! Now we have an experimentally tractable system!

an older woman is holding a megaphone in her mouth and says you are old ALT: an older woman is holding a megaphone in her mouth and says you are old

But did you know - pregnancies >35yrs are considered GERIATRIC (!) offensive! This is because fertility declines as women age – why? Turns out it’s not just your bones that stiffen with age…

A mechanical origin for implantation defects in embryos from aged females Women over 35 experience a marked reduction in fertility. The origin of these fertility defects appears to reside in the implantation capacity of the embryo itself, but the mechanistic basis of this i...

First, check out my recent bioRxiv preprint w/ @oweinerlab.bsky.social: www.biorxiv.org/content/10.1...
We find contractility shifts the proportion of implantation-competent embryos from young and aged females. Keep reading this for more info!

See this? This = implanting mouse embryo. Usually this happens inside its mother and is invisible to us, but we can actually watch implantation ex vivo with the hope of understanding why implantation goes awry in embryos of older women. A 🧵...