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观点:单细胞和卵裂期小鼠胚胎通过表达甘氨酸神经递质转运体和甘氨酸门控氯离子通道在高渗输卵管液中茁壮成长:临床及跨代影响

Perspective: One-Cell and Cleavage-Stage Mouse Embryos Thrive in Hyperosmotic Oviductal Fluid Through Expression of a Glycine Neurotransmitter Transporter and a Glycine-Gated Chloride Channel: Clinical and Transgenerational Implications.

作者信息

Van Winkle Lon J

机构信息

Department of Biochemistry, Midwestern University, Downers Grove, IL, United States.

Department of Medical Humanities, Rocky Vista University, Parker, CO, United States.

出版信息

Front Physiol. 2020 Dec 21;11:613840. doi: 10.3389/fphys.2020.613840. eCollection 2020.

Abstract

The osmolality of mouse oviductal fluid ranges from about 300 mOsmol/kg in the ampulla 0-3 h post coitus (h p.c.) to more than 350 mOsmol/kg in the isthmus 34-36 h p.c. Thus, it has been surprising to find that development of one-cell and cleavage-stage mouse embryos arrests in media exceeding 300 mOsmol/kg, and they develop best in unphysiological, hypotonic media. The glycine concentration in oviductal fluid can, however, rescue development in hypertonic media, so physiological conditions and likely work together to foster embryo well-being. Glycine acts on one-cell and cleavage-stage mouse embryos through the glycine-gated chloride channel, GLRA4, and uptake the glycine neurotransmitter transporter, GLYT1. Since these processes lead to further signaling in neurons, the presence and function of such signaling in preimplantation embryos also should be investigated. The more we know about the interactions of physiological processes and conditions , the better we would be able to reproduce them . Such improvements in assisted reproductive technology (ART) could improve patient outcomes for IVF and potentially help prevent unwanted developmental abnormalities in early embryos, which might include undesirable epigenetic DNA and histone modifications. These epigenetic modifications may lead to transgenerational adult disorders such as metabolic syndrome and related conditions.

摘要

小鼠输卵管液的渗透压在交配后0 - 3小时(h p.c.)壶腹部约为300 mOsmol/kg,而在交配后34 - 36小时峡部则超过350 mOsmol/kg。因此,令人惊讶的是,单细胞和卵裂期小鼠胚胎在渗透压超过300 mOsmol/kg的培养基中发育会停滞,而在非生理性的低渗培养基中发育最佳。然而,输卵管液中的甘氨酸浓度可以挽救高渗培养基中的胚胎发育,所以生理条件可能共同作用以促进胚胎健康。甘氨酸通过甘氨酸门控氯离子通道GLRA4作用于单细胞和卵裂期小鼠胚胎,并通过甘氨酸神经递质转运体GLYT1摄取甘氨酸。由于这些过程会导致神经元中进一步的信号传导,因此也应该研究此类信号传导在植入前胚胎中的存在和功能。我们对生理过程和条件相互作用了解得越多,就越能更好地重现它们。辅助生殖技术(ART)的此类改进可以改善体外受精患者的治疗效果,并有可能帮助预防早期胚胎中不必要的发育异常,这可能包括不良的表观遗传DNA和组蛋白修饰。这些表观遗传修饰可能导致跨代成人疾病,如代谢综合征及相关病症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed41/7779613/877e76d7ae34/fphys-11-613840-g001.jpg

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