Obesity modulates cell-cell interactions during ovarian folliculogenesis

Summary: Obesity is known to affect female reproduction, as evidenced by obese patients suffering from subfertility and abnormal oogenesis. However, the underlying mechanisms by which obesity impairs folliculogenesis are poorly documented. Here, we performed comprehensive single-cell transcriptome a...

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Main Authors: Xin Long, Qiuyun Yang, Jingjing Qian, Huiying Yao, Rui Yan, Xin Cheng, Qiancheng Zhang, Chan Gu, Fei Gao, Hongmei Wang, Lin Zhang, Fan Guo
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221015972
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author Xin Long
Qiuyun Yang
Jingjing Qian
Huiying Yao
Rui Yan
Xin Cheng
Qiancheng Zhang
Chan Gu
Fei Gao
Hongmei Wang
Lin Zhang
Fan Guo
author_facet Xin Long
Qiuyun Yang
Jingjing Qian
Huiying Yao
Rui Yan
Xin Cheng
Qiancheng Zhang
Chan Gu
Fei Gao
Hongmei Wang
Lin Zhang
Fan Guo
author_sort Xin Long
collection DOAJ
description Summary: Obesity is known to affect female reproduction, as evidenced by obese patients suffering from subfertility and abnormal oogenesis. However, the underlying mechanisms by which obesity impairs folliculogenesis are poorly documented. Here, we performed comprehensive single-cell transcriptome analysis in both regular diet (RD) and obese mouse models to systematically uncover how obesity affects ovarian follicle cells and their interactions. We found an increased proportion of Inhbb highly expressed granulosa cells (GCs) among all the GC subpopulations in obese mice. Under obese conditions, excessive androgen secreted from endocrine theca cells (ETCs) may contribute to the imbalanced change of GC subtypes through ETCs-GCs interactions. This is alleviated by enzalutamide, an androgen receptor antagonist. We also identified and confirmed typical GC markers, such as Marcks and Prkar2b, for sensitive evaluation of female fertility in obesity. These data represent a resource for studying transcriptional networks and cell-cell interactions during folliculogenesis under physiological and pathological conditions.
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spelling doaj.art-ce74a901b51847b4a440c19829caa38d2022-12-21T21:40:03ZengElsevieriScience2589-00422022-01-01251103627Obesity modulates cell-cell interactions during ovarian folliculogenesisXin Long0Qiuyun Yang1Jingjing Qian2Huiying Yao3Rui Yan4Xin Cheng5Qiancheng Zhang6Chan Gu7Fei Gao8Hongmei Wang9Lin Zhang10Fan Guo11State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, ChinaWest China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaWest China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaWest China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China; West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Corresponding authorState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authorSummary: Obesity is known to affect female reproduction, as evidenced by obese patients suffering from subfertility and abnormal oogenesis. However, the underlying mechanisms by which obesity impairs folliculogenesis are poorly documented. Here, we performed comprehensive single-cell transcriptome analysis in both regular diet (RD) and obese mouse models to systematically uncover how obesity affects ovarian follicle cells and their interactions. We found an increased proportion of Inhbb highly expressed granulosa cells (GCs) among all the GC subpopulations in obese mice. Under obese conditions, excessive androgen secreted from endocrine theca cells (ETCs) may contribute to the imbalanced change of GC subtypes through ETCs-GCs interactions. This is alleviated by enzalutamide, an androgen receptor antagonist. We also identified and confirmed typical GC markers, such as Marcks and Prkar2b, for sensitive evaluation of female fertility in obesity. These data represent a resource for studying transcriptional networks and cell-cell interactions during folliculogenesis under physiological and pathological conditions.http://www.sciencedirect.com/science/article/pii/S2589004221015972Biological sciencesEndocrinologyCell biologyTranscriptomics
spellingShingle Xin Long
Qiuyun Yang
Jingjing Qian
Huiying Yao
Rui Yan
Xin Cheng
Qiancheng Zhang
Chan Gu
Fei Gao
Hongmei Wang
Lin Zhang
Fan Guo
Obesity modulates cell-cell interactions during ovarian folliculogenesis
iScience
Biological sciences
Endocrinology
Cell biology
Transcriptomics
title Obesity modulates cell-cell interactions during ovarian folliculogenesis
title_full Obesity modulates cell-cell interactions during ovarian folliculogenesis
title_fullStr Obesity modulates cell-cell interactions during ovarian folliculogenesis
title_full_unstemmed Obesity modulates cell-cell interactions during ovarian folliculogenesis
title_short Obesity modulates cell-cell interactions during ovarian folliculogenesis
title_sort obesity modulates cell cell interactions during ovarian folliculogenesis
topic Biological sciences
Endocrinology
Cell biology
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004221015972
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