诺雷丁龙通过雄激素受体抑制胚胎细胞的发育,导致男性偏差
Xiao-Bing Long1, Wen-Jun Shi1, Chong-Rui Yao1
1SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China.
Aquatic toxicology (Amsterdam, Netherlands)
|June 13, 2023
概括
像诺雷丁 (NET) 这样的孕激素通过与雄激素受体 (AR) 结合来破坏鱼类的性发育. 胺 (FLU) 也结合AR,对抗NET的作用并影响生殖细胞的发育.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 发展生物学 发展生物学
背景情况:
- 表面水中的孕激素会影响鱼的生殖腺发育和性差异化.
- 孕激素诱导的性别分化背后的毒理机制仍然不清楚.
研究的目的:
- 研究诺雷丁龙 (NET) 和胺 (FLU) 对斑马鱼淋巴体分化的影响.
- 阐明孕激素诱导的性别分化的分子机制,重点关注雄激素受体 (AR) 相互作用.
主要方法:
- 斑马鱼在受精后21至49天暴露于NET和FLU.
- 分子对接分析以评估AR结合亲和力和相互作用.
- 对关键生殖细胞发育标记物的基因转录分析.
- 发生性腺发育的组织学检查.
主要成果:
- NET暴露导致男性偏差,而FLU暴露导致女性偏差.
- 结合NET和FLU暴露的男性百分比下降,表明对抗性.
- 分子对接显示NET和FLU竞争性地与AR结合.
- NET降低了胚胎细胞生物标志物基因转录,而FLU增加了它,与观察到的性别偏差一致.
结论:
- 雄激素受体 (AR) 结合是NET诱导的性别差异化的启动事件.
- NET通过AR抑制胚胎细胞的发育,导致男性偏见.
- NET和FLU对生殖腺区分产生敌对作用,这对于生态风险评估至关重要.
相关概念视频
Testosterone: Functions and Regulation
782
The intricate hormonal interplay essential for male reproductive health begins with the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This hormone prompts the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH targets the Leydig cells in the testes, stimulating them to produce and release testosterone. In concert with testosterone, FSH acts on the Sertoli cells within the seminiferous tubules to facilitate the release of...
782
Nondisjunction
3.9K
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
3.9K
Teratogenicity
2.5K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.5K
Gonadal and Placental Hormones
1.6K
The gonads, namely the testes in males and the ovaries in females, are pivotal in producing gonadal hormones that orchestrate the intricate processes of sexual development and reproduction.
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...
1.6K
Transducer Mechanism: Nuclear Receptors
1.4K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K
Infertility in Males
299
Male infertility affects millions of couples worldwide, arising from various factors that impact different stages of the reproductive process. An endocrine imbalance resulting from conditions like hypogonadism, Klinefelter syndrome, or pituitary disorders can disrupt hormone levels and reduce sperm production. Testicular defects, such as tumors, cryptorchidism, atrophic testes, abnormal sperm morphology, and low sperm count or motility, may arise due to genetic factors, structural...
299


