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

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.

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

10.1101/2021.02.04.429865 ◽

2021 ◽

Author(s):

Alejandro Aguado-García ◽

Daniel A. Priego-Espinosa ◽

Andrés Aldana ◽

Alberto Darszon ◽

Gustavo Martínez-Mekler

Keyword(s):

Mathematical Model ◽

Experimental Verification ◽

Intracellular Signaling ◽

Female Genital Tract ◽

Experimental Studies ◽

Fertility Control ◽

Experimental Results ◽

Loss Of Function ◽

Ion Transporters ◽

Individual Number

AbstractCapacitation is a complex maturation process that 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, synergistic and interference traits that become apparent in the modelling among some components also call for future theoretical and experimental studies.Author SummaryFertilization is one of the fundamental processes for the preservation of life. In mammals sperms undergo a complex process during their passage through the female tract known as capacitation which enables them for fertilization. At the present time it is accepted from experimental observation, though not understood, is that only a fraction of the sperm is capacitated. In this work, by means of a network mathematical model for regulatory spermatozoa intracellular signaling processes involved in mice capacitation, we find that the variability in the distribution of the number of ion transporters intervenes in the regulation of the capacitation fraction. Experimental verification of this suggestion could open a line of research geared to the regulation of the degree of heterogeneity in the number of ion transporters as a fertility control. The model also uncovers through in silico hyperactivation, loss of function and knockout of network elements, synergetic traits which again call for experimental verification.

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Thermotaxis of mammalian sperm cells: A potential navigation mechanism in the female genital tract

Nature Medicine ◽

10.1038/nm0203-149 ◽

2003 ◽

Vol 9 (2) ◽

pp. 149-150 ◽

Cited By ~ 148

Author(s):

Anat Bahat ◽

Ilan Tur-Kaspa ◽

Anna Gakamsky ◽

Laura C. Giojalas ◽

Haim Breitbart ◽

...

Keyword(s):

Genital Tract ◽

Female Genital Tract ◽

Sperm Cells ◽

Mammalian Sperm ◽

Female Genital

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XIV.—Studies on Reproduction in the Albino Mouse. II. Contributions on the Maturation of the Sperm Cells

Proceedings of the Royal Society of Edinburgh ◽

10.1017/s0370164600012232 ◽

1940 ◽

Vol 59 ◽

pp. 145-152 ◽

Cited By ~ 6

Author(s):

Hugo Merton

Keyword(s):

Genital Tract ◽

Vas Deferens ◽

Female Genital Tract ◽

Morphological Characters ◽

Sperm Cells ◽

Physiological Salt Solution ◽

Mammalian Sperm ◽

Long Time ◽

Slow Passage ◽

Female Genital

The morphological characters of mammalian sperm cells taken from the ductuli efferentes differ only slightly from the sperm derived from the vas deferens. However, it is known that spermatozoa from the caput epididymis, when kept in physiological salt solution, quickly become immotile, whereas those from the cauda epididymis retain their motility for a long time (Moore, 1928). During the slow passage through the epididymis the spermatozoa undergo a physiological process of maturation, which is said to occur under the influence of the epithelium of the epididymis and to result in a lesser susceptibility on the part of the spermatozoa to extraneous influences (Braus and Redenz, 1924; Redenz, 1926; and Lanz, 1929). Other authors maintain that this maturation of the spermatozoon is not conditioned by environmental influences (Young, 1931). In any case the spermatozoa achieve full functional ability only after they have reached the cauda epididymis and the vas deferens. These are the spermatozoa which enter the female genital tract at copulation, and thus it follows that spermatozoa for artificial insemination in the mouse must be taken from the vas deferens and cauda epididymis.

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Possibilities of application of regenerative technologies in gynecology

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1171 ◽

2020 ◽

Vol 75 (1) ◽

pp. 4-17

Author(s):

Julia V. Denisova ◽

Ekaterina V. Mandra ◽

Aleksey V. Lyundup ◽

Yana Y. Sulina ◽

Leonid S. Aleksandrov ◽

...

Keyword(s):

Pelvic Organ Prolapse ◽

Genital Tract ◽

Cellular Therapy ◽

Female Genital Tract ◽

Experimental Studies ◽

Pelvic Organ ◽

Ovarian Failure ◽

Female Reproductive System ◽

Biological Scaffolds ◽

Female Genital

The article presents a review of publications devoted to the use of regenerative technologies in the treatment of gynecological pathologies. The authors describe possible ways to solve these problems by analyzing the experimental studies conducted in the world. Identified the main indications for tissue engineering: Ashermans syndrome, primary ovarian failure, infertility caused by chemotherapy, a niche in the uterus, endometrial pathology (endometriosis, endometrial problems, etc.), cervical pathology, female genital tract abnormalities, pelvic organ prolapse. The results of clinical trials of cell therapy aimed at treating infertility caused by Asherman syndrome and primary ovarian failure, female genital tract abnormalities, as well as such rare pathology as a niche of the uterus. At the preclinical stage, in addition to the above, considered cellular therapy of cervical pathologies, endometrial diseases and pelvic organ prolapse. Eximined cell cultures and the level of their influence on the regeneration of the female reproductive system structures, presented the biological scaffolds that stimulate the growth of stem cells, their effectiveness and shortcomings are covered.

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Membranes of Mammalian Sperm and Capacitation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010009004x ◽

1976 ◽

Vol 34 ◽

pp. 12-13

Author(s):

M. Gordon

Keyword(s):

Cell Membrane ◽

Outer Membrane ◽

Genital Tract ◽

Acrosome Reaction ◽

Female Genital Tract ◽

Cytochemical Analysis ◽

Mammalian Sperm ◽

Female Genital

Capacitation prepares the mammalian sperm for interaction with the ovum. It occurs in the female genital tract and involves a change in the properties of the membrane over the head. The head membranes are morphologically specialized in different regions. The portion overlying the acrosome is loose and not linked to a cytoplasmic substratum (Fig. 1). It is differentiated from the tight membrane apposed to the post acrosomal cap (PAC) (1). Following capacitation, the periacrosomal segment fuses with the outer membrane of the acrosome allowing escape of the acrosomal contents, the “acrosome reaction”. The fertilizing sperm contacts the vitellus at the PAC. Thus the outer membrane is separated into a portion concerned with the loss of the acrosome and another with ovum contact. The outer membrane of the acrosome is distinguished from the inner since it participates in the acrosome reaction. Cytochemical analysis of the cell membrane supports the concept that the stimulus for capacitation is a change in the properties of the plasmalemma induced by fluids of the female tract.

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Cyclic Nucleotide-Specific Optogenetics Highlights Compartmentalization of the Sperm Flagellum into cAMP Microdomains

Cells ◽

10.3390/cells8070648 ◽

2019 ◽

Vol 8 (7) ◽

pp. 648 ◽

Cited By ~ 4

Author(s):

Diana N. Raju ◽

Jan N. Hansen ◽

Sebastian Rassmann ◽

Birthe Stüven ◽

Jan F. Jikeli ◽

...

Keyword(s):

Genital Tract ◽

Physiological Function ◽

Female Genital Tract ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Sperm Capacitation ◽

Pharmacological Interventions ◽

Sperm Flagellum ◽

Mammalian Sperm ◽

Female Genital

Inside the female genital tract, mammalian sperm undergo a maturation process called capacitation, which primes the sperm to navigate across the oviduct and fertilize the egg. Sperm capacitation and motility are controlled by 3′,5′-cyclic adenosine monophosphate (cAMP). Here, we show that optogenetics, the control of cellular signaling by genetically encoded light-activated proteins, allows to manipulate cAMP dynamics in sperm flagella and, thereby, sperm capacitation and motility by light. To this end, we used sperm that express the light-activated phosphodiesterase LAPD or the photo-activated adenylate cyclase bPAC. The control of cAMP by LAPD or bPAC combined with pharmacological interventions provides spatiotemporal precision and allows to probe the physiological function of cAMP compartmentalization in mammalian sperm.

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