Integrated single-cell and spatial transcriptomics reveal microenvironment disruptions by androgen in mouse ovary
Man Luo,
Xiaofeng Yang,
Mengsi Zhou,
Jing Zhang,
Biao Yu,
Hongkai Lian,
Jianping Ye
Affiliations
Man Luo
Institute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China; Corresponding author
Xiaofeng Yang
Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
Mengsi Zhou
Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
Jing Zhang
Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230036, China
Biao Yu
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Hongkai Lian
Institute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
Jianping Ye
Institute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; Zhengzhou Key Laboratory for Obesity Research, Zhengzhou 450007, China; Corresponding author
Summary: Elevated levels of androgen are risk factors for disrupted follicular maturation in the polycystic ovary syndrome (PCOS), a reproductive disease in women. As essential cell types for follicular maturation, granulosa and thecal cells respond to androgen, but their responses are unclear at the subpopulation level. Using single-cell RNA sequencing and spatial transcriptomics, we examined the subpopulation and function alterations in an androgen-induced PCOS-like mouse model. The results demonstrated that the granulosa cell subset 5 (GC5) was active in inflammation and the thecal cell subtype 2 (TC2) had an enhanced activity in lipid metabolism. The two subsets were expanded in population size and intercellular signaling pathways, such as Ptn-Ncl and Mdk-Ncl. The results reveal that androgen induced landscape and function shifts in the two cell types under the condition of impaired follicular maturation. The study characterizes the ovarian microenvironment in responses to androgen in PCOS mice.
