Aldana Andrés, Carneiro Jorge, Martínez-Mekler Gustavo, Darszon Alberto
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.
Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Physiol. 2021 Jul 19;12:682790. doi: 10.3389/fphys.2021.682790. eCollection 2021.
The acrosome reaction (AR) is an exocytotic process essential for mammalian fertilization. It involves diverse physiological changes (biochemical, biophysical, and morphological) that culminate in the release of the acrosomal content to the extracellular medium as well as a reorganization of the plasma membrane (PM) that allows sperm to interact and fuse with the egg. In spite of many efforts, there are still important pending questions regarding the molecular mechanism regulating the AR. Particularly, the contribution of acrosomal alkalinization to AR triggering physiological conditions is not well understood. Also, the dependence of the proportion of sperm capable of undergoing AR on the physiological heterogeneity within a sperm population has not been studied. Here, we present a discrete mathematical model for the human sperm AR based on the physiological interactions among some of the main components of this complex exocytotic process. We show that this model can qualitatively reproduce diverse experimental results, and that it can be used to analyze how acrosomal pH (pH ) and cell heterogeneity regulate AR. Our results confirm that a pH increase can on its own trigger AR in a subpopulation of sperm, and furthermore, it indicates that this is a necessary step to trigger acrosomal exocytosis through progesterone, a known natural inducer of AR. Most importantly, we show that the proportion of sperm undergoing AR is directly related to the detailed structure of the population physiological heterogeneity.
顶体反应（AR）是哺乳动物受精所必需的胞吐过程。它涉及多种生理变化（生化、生物物理和形态学），最终导致顶体内容物释放到细胞外介质中，以及质膜（PM）的重组，使精子能够与卵子相互作用并融合。尽管进行了许多努力，但关于调节AR的分子机制仍存在重要的悬而未决的问题。特别是，顶体碱化对AR触发生理条件的贡献尚未得到很好的理解。此外，能够发生AR的精子比例对精子群体内生理异质性的依赖性也尚未得到研究。在此，我们基于这一复杂胞吐过程中一些主要成分之间的生理相互作用，提出了一个人类精子AR的离散数学模型。我们表明，该模型能够定性地重现各种实验结果，并且可用于分析顶体pH值（pH ）和细胞异质性如何调节AR。我们的结果证实，pH值升高本身可在一部分精子中触发AR，此外，这表明这是通过孕酮（一种已知的AR天然诱导剂）触发顶体胞吐作用的必要步骤。最重要的是，我们表明发生AR的精子比例与群体生理异质性的详细结构直接相关。
