Loss-of-function mutations with circadian rhythm regulator Per1/Per2 lead to premature ovarian insufficiency†

Zheng, Yating; Liu, Chao; Li, Yan; Jiang, Haijuan; Yang, Peixin; Tang, Jing; Xu, Ying; Wang, Han; He, Yulong

doi:10.1093/biolre/ioy245

Cited by 29 publications

(30 citation statements)

References 28 publications

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“…Aging single mutation female Per1 −/− and Per2 −/− mice, bear smaller litters than their WT counterparts. In addition, aging Per1 m/m /Per2 m/m double mutation mice have a significantly reduced number of ovarian follicles, displaying a decrease in female fertility starting approximately at 20 weeks and have significantly fewer pups born from 32 weeks old and onwards [77]. The Per2 oscillation was increased in uteri endometrial stromal cells (UESCs) during implantation, and decreased during differentiation [78].…”

Section: Per1 1 2 Andmentioning

confidence: 99%

Circadian Clock, Time-Restricted Feeding and Reproduction

Pan

Taylor

Cohen

et al. 2020

IJMS

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The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

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Section: Per1 1 2 Andmentioning

confidence: 99%

Circadian Clock, Time-Restricted Feeding and Reproduction

Pan

Taylor

Cohen

et al. 2020

IJMS

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“…PER1 has a role in feeding and active behavior in mammals and is controlled by circadian rhythms (Kim et al, 2020). From a non-tumor perspective, PER1 is related to conditions such as Parkinson's disease, obesity, sleep, drug resistance, and premature ovarian insufficiency (Zheng et al, 2019;Delgado-Lara et al, 2020;EmeklI et al, 2020;Mabrouk et al, 2020;Arellanes-Licea et al, 2021). PER1 enhances the activity of GPX through the interaction of PER1 and GPX1 in the cytoplasm, thereby improving the oxidative phosphorylation efficiency of mitochondria (Sun et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

et al. 2021

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Background: Period circadian protein homolog 1 (PER1) is an important component of the biorhythm molecular oscillation system and plays an important part in the development and progression of mammalian cancer. However, the correlations of PER1 with prognosis and tumor-infiltrating lymphocytes in ovarian cancer (OV) remain unclear.Methods: The Oncomine and TIMER databases were used to examine the expression of PER1 in OV. Kaplan–Meier Plotter and PrognoScan were used to evaluate the relationship between PER1 and prognosis. Kaplan–Meier Plotter was used to analyze the relationships between PER1 and clinicopathological features of OV patients. The relationship between PER1 expression and immune infiltration in OV was investigated using the TIMER database and CIBERSORT algorithm. The STRING database was used to analyze PER1-related protein functional groups, the GeneMANIA online tool was used to analyze gene groups with similar functions to those of PER1, and Network Analyst was used to identify transcription factors that regulate PER1. The correlation between PER1 and immunoinvasion of OV was analyzed using TIMER. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect PER1 expression.Results: PER1 was differentially expressed in different cancer tissues, and its expression in various OV subtypes was lower than that in normal ovarian tissue. OV patients with low PER1 expression had a reduced overall survival rate. Decreased PER1 expression in stage 1 and stage 1+2 OV patients was related to poor prognosis, while increased PER1 expression in stage 3+4 patients and TP53 mutation were related to poor overall survival and progression-free survival. We identified eight genes whose expression was strongly correlated with that of PER1, as well as four transcription factors that regulate PER1. In OV, PER1 expression levels were positively correlated with infiltration levels of cells including neutrophils, regulatory T cells, and M2 macrophages, and closely related to a variety of immune markers. Reduced expression of PER1 was significantly associated with poor overall survival.Conclusion: These findings suggest that PER1 could be used as a prognostic biomarker to determine prognosis and immune infiltration in OV patients.

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“…As is well recognized, the circadian rhythm is an indispensable timing system in the body, which drives the daily oscillations of a variety of critical cellular and physiological processes, such as the cell cycle and its regulators, energy metabolism, cardiovascular function, sleep-wake rhythms, insulin secretion, hormone secretion, and even reproduction. [39][40][41][42][43] Therefore, the transcription level of the circadian rhythm gene in the P4 exposed group may have negatively affected gonad development in juvenile Yellow River Carp, which in turn impacted their reproduction.…”

Section: Discussionmentioning

confidence: 99%

Progesterone affects sex differentiation and alters transcriptional of genes along circadian rhythm signaling and hypothalamic‐pituitary‐gonadal axes in juvenile Yellow River Carp (Cyprinus carpio var.)

Xia

Wang

Wan

et al. 2019

Environmental Toxicology

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Progesterone (P4) is a biologically active steroid hormone that is involved in the regulation of oocyte growth and maturation, as well as development of the endometrium and implantation in the uterus of humans. It can also stimulate oocyte maturation in female fish, as well as spermatogenesis and sperm motility in male fish. Thus, P4 has been extensively used in human and animal husbandry as a typical progestin. However, P4 remaining in the water environment will pose a potential hazard to aquatic organisms. For example, it can interfere with sex differentiation and reproduction in aquatic vertebrates such as fish. Therefore, we investigated the effects of prolonged progesterone exposure on the expression of genes related to circadian rhythm signaling and the hypothalamic‐pituitary‐gonadal (HPG) axes in Yellow River Carp, which may have a potential impact on their sex differentiation. Our results suggested that P4 exposure altered the expression of genes related to circadian rhythm signaling, which can lead to disorders in the endocrine system and regulate the HPG axes‐related activities. Furthermore, the expression of genes related to the HPG axes was also altered, which might affect gonadal development and the reproductive systems of Yellow River Carp. In addition, these changes may provide a plausible mechanism for the observed shifts in their sex ratio toward females.

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Loss-of-function mutations with circadian rhythm regulator Per1/Per2 lead to premature ovarian insufficiency†

Cited by 29 publications

References 28 publications

Circadian Clock, Time-Restricted Feeding and Reproduction

Circadian Clock, Time-Restricted Feeding and Reproduction

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

Progesterone affects sex differentiation and alters transcriptional of genes along circadian rhythm signaling and hypothalamic‐pituitary‐gonadal axes in juvenile Yellow River Carp (Cyprinus carpio var.)

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