MIG-23 is involved in sperm migration in Ascaris suum

Sperm motility acquisition during maturation is essential for successful fertilization.Extracellular adenosine-5'-triphosphate (ATP) level mediation by MIG-23, which is a homolog of human ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), was required for major sperm protein filament dynamics and sperm motility in the nematode Ascaris suum. MIG-23 was localized on the sperm plasma membrane. During sperm activation, mitochondrial activity was increased dramatically, and a large amount of ATP was produced and stored in refringent granules (RGs). In addition, a portion of the produced ATP was released to the extracellular space through ATP channels, which were composed of innexins and localized on the sperm plasma membrane. Spermatozoa, instead of spermatids, hydrolyzed exogenous ATP and processed ecto-ATPase activity. MIG-23 contributed to the ecto-ATPase activity of spermatozoa. MIG-23 activity was interrupted, spermatozoa also decreased their ATP hydrolysis activity. Blocking MIG-23 activity resulted in an increase in the depolymerization rate of MSP filaments in pseudopodia, which eventually affected nematode sperm migration. Overall, our data imply that MIG-23, which contributes to the ecto-ATPase activity of spermatozoa, regulates sperm migration by modulating extracellular ATP levels.

Role of Integrins in Sperm Activation and Fertilization

In mammals, integrins are heterodimeric transmembrane glycoproteins that represent a large group of cell adhesion receptors involved in cell–cell, cell–extracellular matrix, and cell–pathogen interactions. Integrin receptors are an important part of signalization pathways and have an ability to transmit signals into and out of cells and participate in cell activation. In addition to somatic cells, integrins have also been detected on germ cells and are known to play a crucial role in complex gamete-specific physiological events, resulting in sperm-oocyte fusion. The main aim of this review is to summarize the current knowledge on integrins in reproduction and deliver novel perspectives and graphical interpretations presenting integrin subunits localization and their dynamic relocation during sperm maturation in comparison to the oocyte. A significant part of this review is devoted to discussing the existing view of the role of integrins during sperm migration through the female reproductive tract; oviductal reservoir formation; sperm maturation processes ensuing capacitation and the acrosome reaction, and their direct and indirect involvement in gamete membrane adhesion and fusion leading to fertilization.

Mammalian sperm hyperactivation regulates navigation via physical boundaries and promotes pseudo-chemotaxis

Mammalian sperm migration within the complex and dynamic environment of the female reproductive tract toward the fertilization site requires navigational mechanisms, through which sperm respond to the tract environment and maintain the appropriate swimming behavior. In the oviduct (fallopian tube), sperm undergo a process called “hyperactivation,” which involves switching from a nearly symmetrical, low-amplitude, and flagellar beating pattern to an asymmetrical, high-amplitude beating pattern that is required for fertilization in vivo. Here, exploring bovine sperm motion in high–aspect ratio microfluidic reservoirs as well as theoretical and computational modeling, we demonstrate that sperm hyperactivation, in response to pharmacological agonists, modulates sperm–sidewall interactions and thus navigation via physical boundaries. Prior to hyperactivation, sperm remained swimming along the sidewalls of the reservoirs; however, once hyperactivation caused the intrinsic curvature of sperm to exceed a critical value, swimming along the sidewalls was reduced. We further studied the effect of noise in the intrinsic curvature near the critical value and found that these nonthermal fluctuations yielded an interesting “Run–Stop” motion on the sidewall. Finally, we observed that hyperactivation produced a “pseudo-chemotaxis” behavior, in that sperm stayed longer within microfluidic chambers containing higher concentrations of hyperactivation agonists.

Sperm migration in the genital tract—In silico experiments identify key factors for reproductive success

Sperm migration in the female genital tract controls sperm selection and, therefore, reproductive success as male gametes are conditioned for fertilization while their number is dramatically reduced. Mechanisms underlying sperm migration are mostly unknown, since in vivo investigations are mostly unfeasible for ethical or practical reasons. By presenting a spatio-temporal model of the mammalian female genital tract combined with agent-based description of sperm motion and interaction as well as parameterizing it with bovine data, we offer an alternative possibility for studying sperm migration in silico. The model incorporates genital tract geometry as well as biophysical principles of sperm motion observed in vitro such as positive rheotaxis and thigmotaxis. This model for sperm migration from vagina to oviducts was successfully tested against in vivo data from literature. We found that physical sperm characteristics such as velocity and directional stability as well as sperm-fluid interactions and wall alignment are critical for success, i.e. sperms reaching the oviducts. Therefore, we propose that these identified sperm parameters should be considered in detail for conditioning sperm in artificial selection procedures since the natural processes are normally bypassed in reproductive in vitro technologies. The tremendous impact of mucus flow to support sperm accumulation in the oviduct highlights the importance of a species-specific optimum time window for artificial insemination regarding ovulation. Predictions from our extendable in silico experimental system will improve assisted reproduction in humans, endangered species, and livestock.

Sperm migration, selection, survival and fertilizing ability in the mammalian oviduct

In vitro fertilization (IVF) gives rise to embryos in a number of mammalian species and is currently widely used for assisted reproduction in humans and for genetic purposes in cattle. However, the rate of polyspermy is generally higher in vitro than in vivo and IVF remains ineffective in some domestic species like pigs and horses, highlighting the importance of the female reproductive tract for gamete quality and fertilization. In this review, the way the female environment modulates sperm selective migration, survival and acquisition of fertilizing ability in the oviduct is being considered under six aspects: (1) the utero-tubal junction which selects a sperm sub-population entering the oviduct; (2) the presence of sperm binding sites on luminal epithelial cells in the oviduct, which prolong sperm viability and plays a role in limiting polyspermic fertilization; (3) the contractions of the oviduct, which promote sperm migration toward the site of fertilization in the ampulla; (4) the regions of the oviduct, which play different roles in regulating sperm physiology and interactions with oviduct epithelial cells; (5) the time of ovulation and (6) the steroid hormonal environment which regulates sperm release from the luminal epithelial cells and facilitates capacitation in a finely orchestrated manner.

Co-Adaptation of Physical Attributes of the Mammalian Female Reproductive Tract and Sperm to Facilitate Fertilization

The functions of the female reproductive tract not only encompass sperm migration, storage, and fertilization, but also support the transport and development of the fertilized egg through to the birth of offspring. Further, because the tract is open to the external environment, it must also provide protection against invasive pathogens. In biophysics, sperm are considered “pusher microswimmers”, because they are propelled by pushing fluid behind them. This type of swimming by motile microorganisms promotes the tendency to swim along walls and upstream in gentle fluid flows. Thus, the architecture of the walls of the female tract, and the gentle flows created by cilia, can guide sperm migration. The viscoelasticity of the fluids in the tract, such as mucus secretions, also promotes the cooperative swimming of sperm that can improve fertilization success; at the same time, the mucus can also impede the invasion of pathogens. This review is focused on how the mammalian female reproductive tract and sperm interact physically to facilitate the movement of sperm to the site of fertilization. Knowledge of female/sperm interactions can not only explain how the female tract can physically guide sperm to the fertilization site, but can also be applied for the improvement of in vitro fertilization devices.

Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review

Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The present review is focused on analyzing the role played by this important channel in the post-ejaculatory life of spermatozoa, where it has been described to be involved in events such as capacitation, acrosome reaction, calcium trafficking, sperm migration, and fertilization. By performing an exhaustive bibliographic search, this review gathers, for the first time, all the modulators of the TRPV1 function that, to our knowledge, were described to date in different species and cell types. Moreover, all those modulators with a relationship with the reproductive process, either found in the female tract, seminal plasma, or spermatozoa, are presented here. Since the sperm migration through the female reproductive tract is one of the most intriguing and less understood events of the fertilization process, in the present work, chemotaxis, thermotaxis, and rheotaxis guiding mechanisms and their relationship with TRPV1 receptor are deeply analyzed, hypothesizing its (in)direct participation during the sperm migration. Last, TRPV1 is presented as a pharmacological target, with a special focus on humans and some pathologies in mammals strictly related to the male reproductive system.

Dissecting the PRSS37 interactome and potential mechanisms leading to ADAM3 loss in PRSS37 null sperm

A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for sperm migration from the uterus into the oviduct and sperm-egg binding in mice. Disruption of PRSS37 results in male infertility concurrent with the absence of mature ADAM3 from cauda epididymal sperm. However, how PRSS37 modulates ADAM3 maturation remains largely unclear. Here, we determine PRSS37 interactome by GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice. Three molecular chaperones (CLGN, CALR3 and PDILT) and three ADAM proteins (ADAM2, ADAM6B and ADAM4) were identified to be interacting with PRSS37. Coincidently, five of them (except ADAM4) have been reported to interact with precursor ADAM3 and regulate its maturation. We further demonstrated that PRSS37 also interacts directly with precursor ADAM3 and its deficiency impedes the association between PDILT and ADAM3. This could contribute to improper translocation of ADAM3 to the germ cell surface, leading to ADAM3 loss in PRSS37 null mature sperm. The understanding of the maturation mechanisms of pivotal sperm plasma membrane proteins will pave the way toward novel strategies for contraception and treatment of unexplained male infertility.

Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration

Transient receptor potential channels-vanilloid receptor 1 (TRPV1) regulates thermotaxis in sperm-oriented motility. We investigated the role of membrane cholesterol (Chol) on TRPV1-mediated human sperm migration. Semen samples were obtained from five normozoospemic healthy volunteers. Sperm membrane Chol content, quantified by liquid chromatography-mass spectrometry, was modified by incubating cells with 2-hydroxypropyl-ß-cyclodextrin (CD) or the complex between CD and Chol (CD:Chol). The effect on sperm migration on a 10 μM capsaicin gradient (CPS), a TRPV1 agonist, was then investigated. Motility parameters were evaluated by Sperm Class Analyser. Intracellular calcium concentration and acrosome reaction were measured by staining with calcium orange and FITC-conjugated anti-CD46 antibody, respectively. TRPV1-Chol interaction was modelled by computational molecular-modelling (MM). CD and CD:Chol, respectively, reduced and increased membrane Chol content in a dose-dependent manner, resulting in a dose-dependent increase and reduction of sperm migration in a CPS gradient. MM confirmed a specific interaction of Chol with a TRPV1 domain that appeared precluded to the Chol epimer epicholesterol (Epi-Chol). Accordingly, CD:Epi-Chol was significantly less efficient than CD:Chol, in reducing sperm migration under CPS gradient. Chol inhibits TRPV1-mediated sperm function by directly interacting with a consensus sequence of the receptor.

Ovarian odorant-like biomolecules in promoting chemotaxis behavior of spermatozoa olfactory receptors during migration, maturation, and fertilization

Background Studies have shown that olfactory receptor genes are the largest in the human genome, which are significantly expressed in olfactory and non-olfactory tissues such as the reproductive systems where they perform many important biological functions. Main body There is growing evidence that bioactive metabolites from the ovary, follicular fluid, and other parts of the female reproductive tract signal the sperm through a series of signal transduction cascades that regulate sperm migration, maturation, and fertilization processes. Several studies have highlighted the role of G-protein-coupled receptors in these cellular processes. Thus, we aimed to summarize the existing evidence describing the physiological role of most prominent exogenous and endogenous biomolecules found in the female reproductive organ in enhancing the chemotaxis behavior of spermatozoa during migration, maturation, and fertilization and also to elucidate the pathological implications of its dysfunctions and the clinical significance in human fertility. Short conclusion In the future, drugs and molecules can be designed to activate these receptors on sperm to facilitate fertility among infertile couples and use as contraceptives.