Author ORCID Identifier(s)
https://orcid.org/0000-0003-4158-595X
Date of Award
7-2025
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
First Advisor
Christine Metz
Abstract
Infertility is a rising health concern that affects approximately 13% of reproductive age women. Advancements in infertility care are limited by our understanding of healthy human endometrial function. Decidualization is the differentiation process of endometrial stromal cells (eSCs) into secretory decidual cells, is essential for pregnancy success, and correlates with a large influx of immune cells during the secretory phase of the menstrual cycle. Uterine natural killer (uNK) cells are the most abundant immune cell of the secretory phase endometrium and have many roles in maintaining endometrial homeostasis including enhancing eSC decidualization, clearing senescent decidual cells, and increasing spiral artery remodeling. However, most functional studies involving human uNK cells are limited by endometrial tissue accessibility. In this study, we developed and validated uNK cell isolation and expansion techniques using menstrual effluent (ME) as a source of endometrial cells, then used these ME-derived uNK cells to investigate interactions between uNK cells and decidualizing eSCs. Cultured, MEderived uNK cells retained phenotypes of biopsy and decidua-derived uNK cells as assessed by flow cytometry, single cell RNA sequencing, and bulk RNA sequencing. uNK cells co-cultured with eSCs stimulated a pro-inflammatory eSC response via IFNg release and mediated contact-dependent eSC remodeling during decidualization. These results indicate that ME is a viable source of uNK cells that can be used in downstream functional analyses, and that uNK cells have a role in mediating eSC inflammation and remodeling during decidualization. In summary, the development of techniques to isolate and study uNK cells from ME greatly expands uNK cell availability and can provide an avenue for greater understanding of mechanisms that contribute to female infertility.
Recommended Citation
Busch, Stephanie, "Immunology and the Endometrium: Understanding Uterine Natural Killer Cell Interactions with Endometrial Stromal Cells During Decidualization Using a Novel Menstrual Effluent-Derived Model" (2025). Donald and Barbara Zucker School of Medicine Theses and Dissertations. 55.
https://academicworks.medicine.hofstra.edu/zsom_dissertations/55