Microscopy Offers a New View into Uterine Repair

About six years ago, Claire Ang, a graduate student in stem cell biologist Kara McKinley’s lab at Harvard University, first observed the mouse uterine tissue under a microscope and fell in love with the organ. “I remember that picture and thinking like, ‘Oh my god, [this] system is amazing. I want to know everything about this,’” recalled Ang.

McKinley’s lab studies the stem and progenitor cells that help the mammalian inner uterine lining—the endometrium—regenerate more than 400 times over the course of a woman’s life after menstruation and pregnancy.¹ Specifically, Ang’s work looked into how the endometrium returns to the preinjury state after these events.

A majority of Ang’s work relied on a spinning disc confocal microscope, wherein hundreds of pinholes on a rotating opaque disc scan a sample, building up an image. “The imaging aspect of this came from my love of just looking at the tissue more than anything, at least at the beginning,” said Ang.

In addition to quenching Ang’s curiosity of seeing the tissue, these confocal images of mouse uterine tissues offered a clearer understanding of the various progenitor cells in repairing injured uterine epithelium.² The findings, which challenge the current knowledge in the field, were recently published in a non-peer-reviewed preprint.

During menstruation, the upper two thirds of the endometrial layer sheds and is replenished eventually, continuing the menstrual cycle. At present, scientists propose that this repair happens due to the contribution of epithelial progenitor cells housed in the endometrial glands adjoining the shed layer.

To better understand these dynamics, Ang and her team carried out lineage tracing of cells within the endometrial glands to track their fate. Ang and her colleagues collected mouse endometrium either undergoing menstruation or injured by ablation and examined the tissue under a microscope. “We were expecting to see large stretches of tissue that didn't have any epithelium because the tissue had shed,” said Ang. But the images that Ang acquired revealed a completely different picture.

They observed epithelial cells surrounding both the outer tissue that was going to be shed and the underlying tissue that would be retained. However, unlike previously hypothesized, these epithelial cells were not coming from the endometrial glands after tissue detachment, revealing that repair and tissue detachment occur concurrently with minimal contribution from endometrial glands.

“So, the entire timeline of the steps of menstruation were just completely different from what we expected to see,” said Ang. They could not have understood this without actually seeing the tissue, she noted. “We finally put together this model from just honestly looking at a lot of images.”

The visually stunning images further added to the appeal. “I love looking at this tissue. I love working on it,” she said. “I feel like I could look at these pictures forever, and I feel like I could work on this model system forever.”