Critical Roles of the Circadian Transcription Factor BMAL1 in Reproductive Endocrinology and Fertility

Jiang, Yin; Li, Shiping; Xu, Wei; Ying, Junjie; Qu, Yi; Jiang, Xiaohui; Zhang, Ayuan; Yan, Yue; Zhou, Ruixi; Ruan, Tiechao; Li, Jinhui; Mu, Dezhi

doi:10.3389/fendo.2022.818272

Cited by 15 publications

(18 citation statements)

References 118 publications

(238 reference statements)

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“…Furthermore, Bmal1 knockout was found to induce ovarian dysplasia, significantly reduce follicle and corpora lutea counts, and impair steroid production in female mice. In Bmal1 knockout male mice, testes, seminal vesicles, and seminiferous tubules are generally reduced in diameter [ 23 – 25 ]. These results suggest a key role for Bmal1 in reproductive endocrinology and fertility, although we lack an understanding of the underlying mechanisms.…”

Section: Overview Of Bmal1mentioning

confidence: 99%

Neural function of Bmal1: an overview

et al. 2023

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Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the biologic clock. Although Bmal1 is well-established as a major regulator of circadian rhythm, a growing number of studies in recent years have shown that dysfunction of Bmal1 underlies a variety of psychiatric, neurodegenerative-like, and endocrine metabolism-related disorders, as well as potential oncogenic roles. In this review, we systematically summarized Bmal1 expression in different brain regions, its neurological functions related or not to circadian rhythm and biological clock, and pathological phenotypes arising from Bmal1 knockout. This review also discusses oscillation and rhythmicity, especially in the suprachiasmatic nucleus, and provides perspective on future progress in Bmal1 research.

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Section: Overview Of Bmal1mentioning

confidence: 99%

Neural function of Bmal1: an overview

et al. 2023

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“…This study demonstrated that mice lacking BMAL1 expression in the uterus can implant embryos but not sustain a pregnancy. The previous studies showed the possible involvement of Bmal1 in regulation of male and female reproductive functions [ 31 , 32 , 33 ]. It was shown that systemic Bmal1 KO female mice can ovulate but both embryo development and ovarian production of progesterone (P4) are not enough to achieve embryo implantation [ 10 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

Ono

Toyoda

Kagami

et al. 2022

IJMS

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Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.

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“…Theca cells are the pacemakers that regulate ovulation timing and transient sensitivity to LH [ 14 ]. In these conditional knockout mice, transient susceptibility to LH was found in littermate controls and granulosa cell-specific Bmal1 knockout mice, but not in theca cell-specific Bmal1 knockouts [ 7 , 74 ]. This indicated that follicle development and ovulation are affected by circadian rhythm disfunction in theca cells ( Table 1 ).…”

Section: Effects Of the Circadian Clock On The Hypothalamic–pituitary...mentioning

confidence: 99%

The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship

Ono

Ando

Daikoku

et al. 2023

IJMS

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The circadian rhythm, which is necessary for reproduction, is controlled by clock genes. In the mouse uterus, the oscillation of the circadian clock gene has been observed. The transcription of the core clock gene period (Per) and cryptochrome (Cry) is activated by the heterodimer of the transcription factor circadian locomotor output cycles kaput (Clock) and brain and muscle Arnt-like protein-1 (Bmal1). By binding to E-box sequences in the promoters of Per1/2 and Cry1/2 genes, the CLOCK-BMAL1 heterodimer promotes the transcription of these genes. Per1/2 and Cry1/2 form a complex with the Clock/Bmal1 heterodimer and inactivate its transcriptional activities. Endometrial BMAL1 expression levels are lower in human recurrent-miscarriage sufferers. Additionally, it was shown that the presence of BMAL1-depleted decidual cells prevents trophoblast invasion, highlighting the importance of the endometrial clock throughout pregnancy. It is widely known that hormone synthesis is disturbed and sterility develops in Bmal1-deficient mice. Recently, we discovered that animals with uterus-specific Bmal1 loss also had poor placental development, and these mice also had intrauterine fetal death. Furthermore, it was shown that time-restricted feeding controlled the uterine clock’s circadian rhythm. The uterine clock system may be a possibility for pregnancy complications, according to these results. We summarize the most recent research on the close connection between the circadian clock and reproduction in this review.

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Critical Roles of the Circadian Transcription Factor BMAL1 in Reproductive Endocrinology and Fertility

Cited by 15 publications

References 118 publications

Neural function of Bmal1: an overview

Neural function of Bmal1: an overview

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship

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