The fallopian tubes—long, slender structures connecting the ovaries and the uterus—play an important role in women’s reproductive health. Their fringed ends collect the egg from the ovary, coaxing it in for fertilization. The fertilized zygote then descends into the uterus for implantation.
Conditions affecting the fallopian tubes can disrupt this process, with serious consequences for reproductive health. For example, tubal infections can result in infertility and ectopic pregnancies, and recent research suggests that high-grade serous ovarian cancers arise in the fallopian tubes.1,2 “Everybody focuses on the ovary or the uterus, [mostly] ignoring the fallopian tubes,” said Ernst Lengyel, a gynecologic oncologist at the University of Chicago. “To get a comprehensive understanding of pelvic health, you have to understand how [the fallopian tubes] work.”
Now, Lengyel and his team have characterized the cellular landscape of healthy fallopian tubes throughout the menstrual cycle and menopause.3 The results, published in Nature Communications, provide a detailed resource that researchers can use to study conditions affecting the fallopian tubes.
“We really need to understand better the normal functioning of [fallopian tubes], but also what happens when it makes that switch to being more at risk of transforming into cancer,” said Kate Lawrenson, a women’s health expert at the University of Texas Health Science Center at San Antonio who was not involved in the study. The findings advance the field’s understanding of the hormonal environment of the fallopian tubes and how the organ changes with menopause, she said.
Previously, Lengyel and his colleagues at the University of Chicago, Anindita Basu and Mengjie Chen, generated a single-cell atlas of healthy postmenopausal fallopian tubes.4 In the present study, the team set out to characterize fallopian tubes from premenopausal women. After collecting samples from patients who underwent surgeries for fibroid removal, Lengyel and his team used single-cell transcriptomics and epigenomics to build a comprehensive cell atlas.
Because the women were at different stages of their menstrual cycles, the researchers could compare their fallopian tube cell profiles. They discovered an enrichment of different cell subtypes and gene profiles. For example, the predominant cell type expressed during the proliferative phase of the menstrual cycle—when the endometrium thickens in preparation for pregnancy—expressed genes linked with regenerative stem cells and protein folding. In contrast, cell populations enriched during the secretory phase—when the endometrium prepares for zygote implantation—expressed genes associated with placental development. Dissecting the molecular interactions revealed that cells in the secretory phase were enriched for pathways that ensure successful fertilization.
The researchers next sought to understand how the cellular landscape changes as women go through menopause. Comparing results from the premenopausal samples with the previously-collected postmenopausal samples revealed that the latter contained fewer epithelial and immune cells and more stromal cells.3 The epithelial cells had reduced expression of antigen-presenting cell surface receptor genes, DNA repair markers, and hormone receptors.
Menopause also altered overall gene expression profiles: Premenopausal samples showed increased expression of genes required for metabolic activity, whereas postmenopausal samples had increased expression of aging- and apoptosis-associated genes.
Lengyel said that while they expected to see cellular and gene profile alterations throughout the menstrual cycle, they did not anticipate such significant postmenopausal changes. “It was surprising to us because we thought that once menopause comes in, [the fallopian tube] is more or less an inactive tissue and doesn't do anything because it has lost its reproductive function.”
Since growing evidence suggests that fallopian tube epithelial cells may be the progenitor cells of high-grade ovarian cancers, the researchers compared their data to cancer genome databases. They found that epithelial cell markers upregulated in postmenopausal women shared some characteristics of ovarian cancer cells, supporting the theory that these may be the cells of origin for ovarian cancer.
“[The results provide] a new look at postmenopausal [fallopian] tubes in a way that they haven’t been looked at before,” said Lawrenson. “And this is going to be really important for understanding which cells are giving rise to ovarian cancer.” However, she noted that this study had a small sample size and that future studies should include more people from diverse backgrounds.
Lengyel said that, so far, they have only identified genes expressed in fallopian tubes. Further studies using three-dimensional cultures of fallopian tubes are needed to test their functional implications. “This is just a dictionary; the book has to be written about it.”
- Rigby CH, et al. The immune cell profile of human fallopian tubes in health and benign pathology: A systematic review. J Reprod Immunol. 2022;152:103646.
- Labidi-Galy SI, et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun. 2017;8(1):1093.
- Weigert M, et al. A cell atlas of the human fallopian tube throughout the menstrual cycle and menopause. Nat Commun. 2025;16(1):372.
- Lengyel E, et al. A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing. Cell Rep. 2022;41(12):111838.
