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Tomomi Kawamura Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Yidan Dai Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Masanori Ono Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Takayuki Kikuchi Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Akina Yamanaka Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Keiko Ueno Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Junya Kojima Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Tomoko Fujiwara Department of Social Work and Life Design, Kyoto Notre Dame University, Kyoto, Japan

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Takiko Daikoku Division of Animal Disease Model, Research Center for Experimental Modeling of Human Disease, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

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Yoshiko Maida Department of Nursing, College of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan

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Hitoshi Ando Department of Cellular and Molecular Function Analysis, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

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Hiroshi Fujiwara Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

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Naoaki Kuji Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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Hirotaka Nishi Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan

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In brief

In this study, we examined the relationship between BMAL1 expression and the genes regulating steroid biosynthesis in human luteinized granulosa cells. BMAL1 function is crucial for steroid production and proper ovarian function, highlighting the importance of circadian clock regulation in female reproductive health.

Abstract

Human luteinized granulosa cells were collected to analyze circadian clock gene expression and its effect on the genes regulating steroid biosynthesis. We used siRNA to knock down the expression of BMAL1 in KGN cells. We measured the expression levels of genes regulating steroid biosynthesis and circadian clock RT-qPCR. We demonstrated that BMAL1 expression positively correlates with genes regulating steroid biosynthesis (CYP11A1, CYP19A1, STAR, and ESR2). The knockdown of BMAL1 in KGN cells revealed a significant decrease in steroid synthase expression. In contrast, when BMAL1 was overexpressed in KGN and HGL5 cells, we observed a significant increase in the expression of steroid synthases, such as CYP11A1 and CYP19A1. These results indicated that BMAL1 positively controls 17β-estradiol (E2) secretion in granulosa cells. We also demonstrated that dexamethasone synchronization in KGN cells enhanced the rhythmic alterations in circadian clock genes. Our study suggests that BMAL1 plays a critical role in steroid biosynthesis in human luteinized granulosa cells, thereby emphasizing the importance of BMAL1 in the regulation of reproductive physiology.

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