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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ion Channels / metabolism*
  • Ion Transport / physiology
  • Male
  • Mice
  • Models, Theoretical*
  • Phosphorylation
  • Sperm Capacitation / physiology*
  • Spermatozoa / metabolism*

Substances

  • Ion Channels

Grants and funding

All authors thank CONACyT for grant CB-2015-01 255914-F7. A.D. performed part of this work while carrying out a Sabbatical at the Instituto Gulbenkian de Ci\^encia (IGC) supported by DGAPA/PASPA/ UNAM and IGC. A.A.A-G. thanks CONACyT for doctoral and mobility fellowships 509572. A.A-G. thanks CONACyT for doctoral fellowship 428858. G.M-M. acknowledges support from DGAPA/PASPA/UNAM for a sabbatical leave at ENS, Paris. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.