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Xin Wen Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Department of Pediatric Urology, Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Jiexia Wang Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Department of Pediatric Urology, Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Mengjie Qin Department of Pharmacology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Hu Wang Zhejiang Provincial Key Laboratory of Anesthesiology, Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Jingfeng Xu Zhejiang Provincial Key Laboratory of Anesthesiology, Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Xiaoju Guan Department of Pediatric Urology, Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Dan Shan Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Panpan Chen Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Jiajia Xie Department of Pharmacology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Jingjing Shao Department of Pharmacology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Ping Duan Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Congde Chen Department of Pediatric Urology, Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Haolin Chen Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Department of Pediatric Urology, Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Department of Pharmacology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Zhejiang Provincial Key Laboratory of Anesthesiology, Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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In brief

Progenitor cells with ovulation-related tissue repair activity were identified with defined markers (LGR5, EPCR, LY6A, and PDGFRA), but their potentials to form steroidogenic cells were not known. This study shows that the cells can generate progenies with different steroidogenic activities.

Abstract

Adult mammalian ovaries contain stem/progenitor cells necessary for folliculogenesis and ovulation-related tissue rupture repair. Theca cells are recruited and developed from progenitors during the folliculogenesis. Theca cell progenitors were not well defined. The aim of current study is to compare the potentials of four ovarian progenitors with defined markers (LY6A, EPCR, LGR5, and PDGFRA) to form steroidogenic theca cells in vitro. The location of the progenitors with defined makers was determined by immunohistochemistry and immunofluorescence staining of ovarian sections of adult mice. Different progenitor populations were purified by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) techniques from ovarian cell preparation and were tested for their abilities to generate steroidogenic theca cells in vitro. The cells were differentiated with a medium containing LH, ITS, and DHH agonist for 12 days. The results showed that EPCR+ and LGR5+ cells primarily distributed along the ovarian surface epithelium (OSE), while LY6A+ cells distributed in both the OSE and parenchyma. However, PDGFRA+ cells were exclusively located in interstitial compartment. When the progenitors were purified by these markers and differentiated in vitro, LY6A+ and PDGFRA+ cells formed steroidogenic cells expressing both CYP11A1 and CYP17A1 and primarily producing androgens, showing characteristics of theca-like cells, while LGR5+ cells generated steroidogenic cells devoid of CYP17A1 expression and androgen production, showing a characteristic of progesterone-producing cells (granulosa- or lutea-like cells). In conclusion, progenitors from both OSE and parenchyma of adult mice are capable of generating steroidogenic cells with different steroidogenic capacities, showing a possible lineage preference.

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Pan-Pan Cheng Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Jun-Jie Xia Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Hai-Long Wang Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Ji-Bing Chen Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Fei-Yu Wang Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Ye Zhang Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Xin Huang Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Quan-Jun Zhang Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Zhong-Quan Qi Organ Transplantation Institute of Xiamen University, Basic Medical Department of Medical College, The Yanwu Branch of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province 361005, People's Republic of China

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Maternal diabetes adversely affects preimplantation embryo development and oocyte maturation. Thus, it is important to identify ways to eliminate the effects of maternal diabetes on preimplantation embryos and oocytes. The objectives of this study were to investigate whether islet transplantation could reverse the effects of diabetes on oocytes. Our results revealed that maternal diabetes induced decreased ovulation; increased the frequency of meiotic spindle defects, chromosome misalignment, and aneuploidy; increased the relative expression levels of Mad2 and Bub1; and enhanced the sensitivity of oocytes to parthenogenetic activation. Islet transplantation prevented these detrimental effects. Therefore, we concluded that islet transplantation could reverse the effects of diabetes on oocytes, and that this technique may be useful to treat the fundamental reproductive problems of women with diabetes mellitus.

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