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by claude@2026-07, 2026-07-09
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This study presents a 2M-cell atlas of the female reproductive system, integrating transcriptomic and spatial data to define 210 cell types, reveal novel cell populations, and link genetic risk variants to specific cell states and disease pathogenesis.
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by claude@2026-07, 2026-07-09
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The paper studied how cell types are distributed across the female reproductive system over the lifespan and menstrual cycle by generating an integrated human female reproductive system cell atlas comprising single-cell transcriptomic data from more than 2 million cells across the ovary, fallopian tube, uterus, cervix, and vagina, further complemented by spatial transcriptomics and chromatin accessibility profiling. Cross-organ analysis identified shared and organ-specific cellular states, including uterine-specific perivascular populations, hypoxia-sensing ILC3s enriched in the uterus, lipid-associated macrophage subsets that differed by organ, and an ectopic endometrial-like epithelial population in a pediatric ovary consistent with early endometriosis. The authors integrated the atlas with GWAS to link risk variants for major gynecological conditions to mesenchymal cell states defined by transcriptional programs and context, and they used chromatin maps to nominate disease effector genes, such as PMOS locus evidence linking to INHBB in granulosa cells. The study’s main limitation is that, despite detection of ectopic cell signatures in donors, it is a reference atlas resource rather than a longitudinal causal experiment. This paper is centrally about endometriosis — it reports detection of endometrial-like cells in a pediatric ovary consistent with early endometriosis within a broader pan-organ reproductive atlas.
Abstract
Single cell transcriptomics has transformed our knowledge of reproductive tissues, yet studies remain largely organ-specific and temporally limited, leaving an incomplete picture of how cell types are distributed across the reproductive system over a lifetime. Gynaecological conditions affect more than one in four females and frequently span multiple organs and life stages. To advance our understanding and treatment of these conditions, an integrated cellular reference is essential. Here we present the Human Female Reproductive System Cell Atlas v1 : a single-cell transcriptomic resource integrating more than 2M cells across the ovary, fallopian tube, uterus, cervix and vagina over the lifespan and menstrual cycle, further integrated with spatial transcriptomics and chromatin accessibility profiling to define 210 cell types through community-based annotation. Cross-organ integration resolves shared and organ-specific cellular states, identifying uterine-specific perivascular populations lining uterine spiral arteries, hypoxia-sensing type 3 innate lymphoid cells (ILC3s) enriched in the uterus, and lipid-associated macrophages with distinct subsets in each reproductive organ, including a previously undescribed population shared between the uterus and fallopian tube. Cross-organ integration enables detection of ectopic epithelial populations in otherwise healthy donors, including endometrial-like cells within a paediatric ovary consistent with early endometriosis. Integration with genome-wide association studies (GWAS) reveals that risk variants for major gynecological conditions act in mesenchymal cell states defined by specific transcriptional programmes and spatial or temporal context – for instance, heavy menstrual bleeding risk is enriched in basal fibroblasts (SFRP5⁺) of the regenerative endometrial compartment. An integrated chromatin accessibility atlas provides peak-to-gene maps across reproductive cell types, enabling nomination of disease effector genes and providing the first regulatory evidence linking a Polyendocrine Metabolic Ovarian Syndrome (PMOS) risk locus to INHBB in granulosa cells. Together, this resource establishes a cellular and molecular framework for reproductive biology and the pathogenesis of neglected gynaecological conditions.
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Abstract
Single cell transcriptomics has transformed our knowledge of reproductive tissues, yet studies remain largely organ-specific and temporally limited, leaving an incomplete picture of how cell types are distributed across the reproductive system over a lifetime. Gynaecological conditions affect more than one in four females and frequently span multiple organs and life stages. To advance our understanding and treatment of these conditions, an integrated cellular reference is essential. Here we present the Human Female Reproductive System Cell Atlas v1: a single-cell transcriptomic resource integrating more than 2M cells across the ovary, fallopian tube, uterus, cervix and vagina over the lifespan and menstrual cycle, further integrated with spatial transcriptomics and chromatin accessibility profiling to define 210 cell types through community-based annotation. Cross-organ integration resolves shared and organ-specific cellular states, identifying uterine-specific perivascular populations lining uterine spiral arteries, hypoxia-sensing type 3 innate lymphoid cells (ILC3s) enriched in the uterus, and lipid-associated macrophages with distinct subsets in each reproductive organ, including a previously undescribed population shared between the uterus and fallopian tube. Cross-organ integration enables detection of ectopic epithelial populations in otherwise healthy donors, including endometrial-like cells within a paediatric ovary consistent with early endometriosis. Integration with genome-wide association studies (GWAS) reveals that risk variants for major gynecological conditions act in mesenchymal cell states defined by specific transcriptional programmes and spatial or temporal context – for instance, heavy menstrual bleeding risk is enriched in basal fibroblasts (SFRP5⁺) of the regenerative endometrial compartment. An integrated chromatin accessibility atlas provides peak-to-gene maps across reproductive cell types, enabling nomination of disease effector genes and providing the first regulatory evidence linking a Polyendocrine Metabolic Ovarian Syndrome (PMOS) risk locus to INHBB in granulosa cells. Together, this resource establishes a cellular and molecular framework for reproductive biology and the pathogenesis of neglected gynaecological conditions.
Competing Interest Statement
S.A.T. is a scientific advisory board member of Bioptimus, ForeSite Labs, Xaira Therapeutics, a co-founder, Board observer and equity holder of TransitionBio, a co-founder, consultant and Board Director of Ensocell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. M.M. holds shares and consults for Emm Technology Ltd. K.T.Z. has received grant income from Aspira Ltd, Bayer AG, Exeltis Ltd, and Proteomics Inc (funds to institution), and acted as a consultant for Gedeon Richter, ZEG Berlin, Roche Inc, and Apikal ltd (fees to institution). E.S-V. is Chief Scientific Officer of the AE-PMOS Society.
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