循环节律扰乱通过NAD+代谢重编程损害了卵巢卵泡的发育
Yan-Yun Ying1, Xin Chen1, Sen-Yi Yao1
1Institute of Medical Genetics and Development, and Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, 310006, China.
EBioMedicine
|March 9, 2026
概括
长时间的光周期暴露会破坏女性的生殖健康,因为它会损害NAD+代谢和卵巢功能. 补充尼古丁胺胺单核酸 (NMN) 可以恢复卵巢功能并改善生育结果.
科学领域:
- 生殖生物学 生殖生物学
- 时间生物学 时间生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 循环节律对人类健康至关重要,尤其是生殖健康.
- 扰乱的昼夜节律与女性不孕症有关,但影响卵巢功能的机制尚不清楚.
- 生活方式中的长光周期 (LP) 暴露可能会破坏自然的光暗周期.
研究的目的:
- 研究长光周期 (LP) 暴露对大鼠毛囊发育和卵巢功能的影响.
- 阐明昼夜干扰对卵巢健康的潜在分子机制.
- 评估尼古丁胺胺 mononucleotide (NMN) 在缓解LP诱导的卵巢功能障碍方面的治疗潜力.
主要方法:
- 鼠被暴露在LP条件下 (18小时的光/6小时的黑暗),以模拟生活方式的光暴露.
- 卵巢功能通过激素水平,雌性周期,形态,卵泡发育和排卵来评估.
- 研究分子机制使用RNA测序,代谢学,ChIP/qPCR,电子显微镜,免疫光学和西部涂抹.
- 评估了NMN补充对LP暴露的老鼠卵巢功能的影响.
主要成果:
- 暴露于LP减少了卵巢毛囊和卵细胞产量,导致颗粒细胞氧化应激和线粒体功能障碍.
- 通过抑制SIRT3活性和SOD2脱乙烯化,LP暴露降低了NAD+水平.
- 由LP暴露引起的循环节障碍通过BMAL1损害了卵巢NAMPT表达,影响了NAD+合成.
- 在暴露于LP的老鼠中,NMN治疗显著增加了腹膜毛囊和检索的卵细胞.
结论:
- 通过LP暴露破坏循环节律,通过失调的NAD+代谢损害了卵巢功能和卵泡发育.
- 准NAD+代谢途径为卵巢疾病提供了一个有前途的治疗策略.
- 恢复NAD+水平可能提供一种新的方法来对抗与昼夜干扰相关的不孕症.
相关概念视频
Hormonal Control of the Ovarian Cycle
7.3K
The ovarian cycle is meticulously regulated by the hypothalamic-pituitary-gonadal axis. This cycle orchestrates the release of a mature oocyte, essential for reproduction.
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
7.3K
Circadian Rhythms and Gene Regulation
4.7K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.7K
Hormonal Regulation of the Menstrual Cycle
2.0K
The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
2.0K
Ovarian Cycle
4.9K
The menstrual cycle includes a critical component known as the ovarian cycle, which undergoes two main phases each month—the follicular phase and the luteal phase. The follicular phase is variable and averaging around 14 days. Ovulation, triggered by a surge in luteinizing hormone (LH), marks the transition between the two phases. The second phase, the luteal phase, is relatively consistent, lasting approximately 14 days, and is marked by the activity of the corpus luteum. While a cycle...
4.9K
Oogenesis
70.9K
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
70.9K
Oogenesis
4.6K
Oogenesis, the process of developing egg cells (female gametes), occurs within the ovaries and is fundamental to female fertility. This sequence begins during fetal development when diploid oogonia in the developing ovaries undergo mitotic divisions to produce primary oocytes. By birth, these primary oocytes enter prophase I of meiosis but become arrested in this stage, remaining suspended until puberty.
Each primary oocyte is surrounded by a layer of pre-granulosa cells, forming what is...
Each primary oocyte is surrounded by a layer of pre-granulosa cells, forming what is...
4.6K


