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数学模型揭示,离子转运体数量的异质性调节了小鼠精子获能的分数。

Mathematical model reveals that heterogeneity in the number of ion transporters regulates the fraction of mouse sperm capacitation.

机构信息

Instituto de Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.

Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

出版信息

PLoS One. 2021 Nov 18;16(11):e0245816. doi: 10.1371/journal.pone.0245816. eCollection 2021.

DOI:10.1371/journal.pone.0245816
PMID:34793454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8601445/
Abstract

Capacitation is a complex maturation process mammalian sperm must undergo in the female genital tract to be able to fertilize an egg. This process involves, amongst others, physiological changes in flagellar beating pattern, membrane potential, intracellular ion concentrations and protein phosphorylation. Typically, in a capacitation medium, only a fraction of sperm achieve this state. The cause for this heterogeneous response is still not well understood and remains an open question. Here, one of our principal results is to develop a discrete regulatory network, with mostly deterministic dynamics in conjunction with some stochastic elements, for the main biochemical and biophysical processes involved in the early events of capacitation. The model criterion for capacitation requires the convergence of specific levels of a select set of nodes. Besides reproducing several experimental results and providing some insight on the network interrelations, the main contribution of the model is the suggestion that the degree of variability in the total amount and individual number of ion transporters among spermatozoa regulates the fraction of capacitated spermatozoa. This conclusion is consistent with recently reported experimental results. Based on this mathematical analysis, experimental clues are proposed for the control of capacitation levels. Furthermore, cooperative and interference traits that become apparent in the modelling among some components also call for future theoretical and experimental studies.

摘要

获能是哺乳动物精子在雌性生殖道中必须经历的一个复杂的成熟过程,以便能够使卵子受精。这个过程涉及到鞭毛摆动模式、膜电位、细胞内离子浓度和蛋白质磷酸化等方面的生理变化。通常,在获能培养基中,只有一部分精子能够达到这种状态。导致这种异质反应的原因尚不清楚,仍是一个悬而未决的问题。在这里,我们的主要结果之一是开发了一个离散的调控网络,该网络主要具有确定性动力学,同时结合了一些随机元素,用于涉及获能早期事件的主要生化和生物物理过程。该模型的获能标准要求特定水平的特定节点集的收敛。除了再现了几个实验结果并提供了对网络相互关系的一些见解外,该模型的主要贡献在于,提示了精子中离子转运体的总量和个体数量的可变性调节了获能精子的比例。这一结论与最近报道的实验结果一致。基于这个数学分析,提出了一些实验线索,以控制获能水平。此外,建模中一些成分之间表现出的合作和干扰特性也需要未来进行理论和实验研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76b/8601445/66e3a2d52e8d/pone.0245816.g007.jpg
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A Minimal Model Shows that a Positive Feedback Loop Between sNHE and SLO3 can Control Mouse Sperm Capacitation.一个最小模型表明,sNHE和SLO3之间的正反馈回路可以控制小鼠精子获能。
Front Cell Dev Biol. 2022 Mar 25;10:835594. doi: 10.3389/fcell.2022.835594. eCollection 2022.
Membrane Potential Determined by Flow Cytometry Predicts Fertilizing Ability of Human Sperm.
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Cyclin-CDK Complexes are Key Controllers of Capacitation-Dependent Actin Dynamics in Mammalian Spermatozoa.细胞周期蛋白-CDK 复合物是哺乳动物精子顶体反应依赖的肌动蛋白动力学的关键控制器。
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