Cyclic Nucleotide-Specific Optogenetics Highlights
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Proteomic Profile of Human Spermatozoa in Healthy And
Cao et al. Reproductive Biology and Endocrinology (2018) 16:16 https://doi.org/10.1186/s12958-018-0334-1 REVIEW Open Access Proteomic profile of human spermatozoa in healthy and asthenozoospermic individuals Xiaodan Cao, Yun Cui, Xiaoxia Zhang, Jiangtao Lou, Jun Zhou, Huafeng Bei and Renxiong Wei* Abstract Asthenozoospermia is considered as a common cause of male infertility and characterized by reduced sperm motility. However, the molecular mechanism that impairs sperm motility remains unknown in most cases. In the present review, we briefly reviewed the proteome of spermatozoa and seminal plasma in asthenozoospermia and considered post-translational modifications in spermatozoa of asthenozoospermia. The reduction of sperm motility in asthenozoospermic patients had been attributed to factors, for instance, energy metabolism dysfunction or structural defects in the sperm-tail protein components and the differential proteins potentially involved in sperm motility such as COX6B, ODF, TUBB2B were described. Comparative proteomic analysis open a window to discover the potential pathogenic mechanisms of asthenozoospermia and the biomarkers with clinical significance. Keywords: Proteome, Spermatozoa, Sperm motility, Asthenozoospermia, Infertility Background fertilization failure [4] and it has become clear that iden- Infertility is defined as the lack of ability to achieve a tifying the precise proteins and the pathways involved in clinical pregnancy after one year or more of unprotected sperm motility is needed [5]. and well-timed intercourse with the same partner [1]. It is estimated that around 15% of couples of reproductive age present with infertility, and about half of the infertil- Application of proteomic techniques in male ity is associated with male partner [2, 3]. -
Testicular Dysgenesis Syndrome: from Human Disorders to Mechanistic Studies in an Animal Model
Conference abstracts. International Symposium on Animal Biology of Reproduction, Nov. 15-18, 2006, Belo Horizonte, Brazil. Testicular dysgenesis syndrome: from human disorders to mechanistic studies in an animal model R. Sharpe, K. Mahood, H. Scott, N. Hallmark, G. Hutchison, C. McKinnell, D. Ferrara MRC Human Reproductive Sciences Unit, Queen’s Medical Research Institute, Edinburgh. Disorders of male reproductive development are fetal Leydig cells towards the centre of the testis and extremely common in humans. They may manifest this migration appears to interfere with the final phases either at birth (cryptorchidism, hypospadias) or in young of seminiferous cord formation and appropriate adulthood (low sperm counts, testicular germ cell testicular cell segregation in the fetal testis. This then cancer). There is reasonable evidence that the incidence leads postnatally to the appearance of focal dysgenetic of most of these disorders has been increasing in recent areas that contain malformed seminiferous cords and decades and it has been hypothesised that they form a intratubular Leydig cells. Wherever the intratubular testicular dysgenesis syndrome (TDS), with a common Leydig cells occur, no germ cells survive and this may origin in fetal life. Each of these disorders is a partly explain the common occurrence of Sertoli cell- significant risk factor for each of the others and they all only tubules within the adult testis of rats exposed in share common, pregnancy-related risk factors. It is utero to DBP. DBP exposure in fetal life also results hypothesised that the disorders arise as a result of in a delay in the normal phases of germ cell maldevelopment of the testis which leads to malfunction development; this is first manifest by delayed entry of the developing Sertoli and Leydig cells in the fetal into quiescence coincident with prolongation of testis with the disorders resulting downstream from this expression of the pluripotency factor OCT4. -
Structure-Based Redesigning of Pentoxifylline Analogs Against
www.nature.com/scientificreports OPEN Structure‑based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies Mutyala Satish1,5, Sandhya Kumari2,5, Waghela Deeksha1, Suman Abhishek1, Kulhar Nitin1, Satish Kumar Adiga2, Padmaraj Hegde3, Jagadeesh Prasad Dasappa4, Guruprasad Kalthur2* & Eerappa Rajakumara1* Phosphodiesterase (PDE) inhibitors, such as pentoxifylline (PTX), are used as pharmacological agents to enhance sperm motility in assisted reproductive technology (ART), mainly to aid the selection of viable sperm in asthenozoospermic ejaculates and testicular spermatozoa, prior to intracytoplasmic sperm injection (ICSI). However, PTX is reported to induce premature acrosome reaction (AR) and, exert toxic efects on oocyte function and early embryo development. Additionally, in vitro binding studies as well as computational binding free energy (ΔGbind) suggest that PTX exhibits weak binding to sperm PDEs, indicating room for improvement. Aiming to reduce the adverse efects and to enhance the sperm motility, we designed and studied PTX analogues. Using structure‑guided in silico approach and by considering the physico‑chemical properties of the binding pocket of the PDEs, designed analogues of PTX. In silico assessments indicated that PTX analogues bind more tightly to PDEs and form stable complexes. Particularly, ex vivo evaluation of sperm treated with one of the PTX analogues (PTXm‑1), showed comparable benefcial efect at much lower concentration—slower -
Chemotaxis: Communication Strategies from Bacteria to Humans
Michael Eisenbach Chemotaxis: Rina Barak Anat Bren Communication strategies Galit Cohen Ben-Lulu Fei Sun from bacteria to humans Jianshe Yan Yael Yosef Department of Biological Chemistry Tel. 972 8 934 3923 Fax. 972 8 934 4112 E-mail: [email protected] Signal transduction in bacterial chemotaxis We explore signal transduction strategies using chemotaxis of the bacteria Escherichia coli and Salmonella typhimurium as a model. Bacterial chemotaxis is a sophisticated system that integrates many different signals into a common output - a change in the direction of flagellar rotation. Our goal is to understand how CheY - a messenger protein that shuttles back and forth between the receptor supramolecular complex and the flagellar-motor supramolecular complex (Fig. 1) - brings about changes in the direction of flagellar rotation. We found that phosphorylation of CheY increases its binding to the switch protein FliM with a consequent increased probability of clockwise rotation, we identified the reciprocal binding domains on FliM and CheY, and we further found that CheY phosphorylation also Fig. 1 Simplified scheme of signal transduction in bacterial chemotaxis regulates the termination of the signal by controlling the activity of E. coli and S. typhimurium. Black arrows stand for regulated of a specific phosphatase, CheZ. Recently we investigated the protein-protein interactions. CheY is a response regulator, CheA is a correlation between the fraction of FliM molecules that are histidine kinase, and CheZ is a phosphatase. occupied by CheY and the probability of clockwise rotation. We found that this probability increases only when most of the FliM provided evidence that CheY acetylation also occurs in vivo molecules are occupied by CheY, and then the change is very and that, in the absence of Acs, chemotaxis is defective. -
Mechanisms of the Sperm Guidance, an Essential Aid for Meeting the Oocyte
430 Editorial Mechanisms of the sperm guidance, an essential aid for meeting the oocyte Raquel Lottero-Leconte*, Carlos Agustín Isidro Alonso*, Luciana Castellano, Silvina Perez Martinez Laboratory of Biology of Reproduction in Mammals, Center for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine, University of Buenos Aires (UBA), Buenos Aires, Argentina *These authors contributed equally to this work. Correspondence to: Silvina Perez Martinez, Senior Investigator. Center for Pharmacological and Botanical Studies, University of Buenos Aires (UBA), School of Medicine, National Scientific and Technical Research Council-Argentina (CONICET), Paraguay 2155, 15th Floor, C1121ABG, Ciudad de Buenos Aires, Argentina. Email: [email protected]. Provenance: This is an invited Editorial commissioned by Section Editor Weijun Jiang (Nanjing Normal University, Department of Reproductive and Genetics, Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China). Comment on: De Toni L, Garolla A, Menegazzo M, et al. Heat Sensing Receptor TRPV1 Is a Mediator of Thermotaxis in Human Spermatozoa. PLoS One 2016;11:e0167622. Submitted Mar 07, 2017. Accepted for publication Mar 14, 2017. doi: 10.21037/tcr.2017.03.68 View this article at: http://dx.doi.org/10.21037/tcr.2017.03.68 In mammals, ejaculated spermatozoa must migrate into the to a temperature gradient (towards the warmer temperature) female reproductive tract in order to reach and fertilize the (Figure 1). Spermatozoa can sense both the absolute ambient oocyte (Figure 1). The number of spermatozoa that reach temperature and the temperature gradient. Previous studies the oviductal isthmus (where they attach to oviductal cells showed that, at peri-ovulation stage, there is a temperature and form the sperm reservoir) is small (1,2) and only ~10% difference between the sperm reservoir site (cooler) and the of these spermatozoa in humans become capacitated (3) fertilization site (warmer). -
SPERM THERMOTAXIS Anat Bahatand Michael Eisenbach
SPERM THERMOTAXIS Anat Bahat and Michael Eisenbach∗ Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel Abstract Thermotaxis — movement directed by a temperature gradient — is a prevalent process, found from bacteria to human cells. In the case of mammalian sperm, thermotaxis appears to be an essential mechanism guiding spermatozoa, released from the cooler reservoir site, towards the warmer fertilization site. Only capacitated spermatozoa are thermotactically responsive. Thermotaxis appears to be a long-range guidance mechanism, additional to chemotaxis, which seems to be short-range and likely occurs at close proximity to the oocyte and within the cumulus mass. Both mechanisms probably have a similar function — to guide capacitated, ready-to- fertilize spermatozoa towards the oocyte. The temperature difference between the site of the sperm reservoir and the fertilization site is generated at ovulation by a temperature drop at the former. The molecular mechanism of sperm thermotaxis waits to be revealed. Keywords: Thermotaxis (sperm); Guidance (sperm); Thermosensing (sperm); Fertilization; Spermatozoa (mammalian); Female genital tract. ∗ Corresponding author. Tel: +972-8-934-3923; fax: +972-8-947-2722. E-mail address: [email protected] (M. Eisenbach). 1. Introduction A new life begins after the sperm cell (spermatozoon) meets the oocyte and initiates a series of processes that leads to sperm penetration, sperm-oocyte fusion, and zygote division. However, the chance of an incidental encounter between the gametes is very slim (Eisenbach and Tur-Kaspa, 1999; Hunter, 1993) due to a number of reasons. First, the number of ejaculated spermatozoa that reach the oviductal isthmus [where they become trapped and form a sperm reservoir (Suarez, 2002)] is small (Harper, 1982). -
Sperm Motility, Oxidative Status, and Mitochondrial Activity: Exploring Correlation in Different Species
antioxidants Article Sperm Motility, Oxidative Status, and Mitochondrial Activity: Exploring Correlation in Different Species Alessandra Gallo 1,* , Maria Consiglia Esposito 1 , Elisabetta Tosti 1 and Raffaele Boni 1,2,* 1 Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy; [email protected] (M.C.E.); [email protected] (E.T.) 2 Department of Sciences, University of Basilicata, 85100 Potenza, Italy * Correspondence: [email protected] (A.G.); [email protected] (R.B.); Tel.: +39-081-5833233 (A.G.); +39-0971-205017 (R.B.) Abstract: Sperm quality assessment is the first step for evaluating male fertility and includes the estimation of sperm concentration, motility, and morphology. Nevertheless, other parameters can be assessed providing additional information on the male reproductive potential. This study aimed to evaluate and correlate the oxidative status, mitochondrial functionality, and motility in sperma- tozoa of two marine invertebrate (Ciona robusta and Mytilus galloprovincialis) and one mammalian (Bos taurus) species. By combining fluorescent staining and spectrofluorometer, sperm oxidative status was evaluated through intracellular reactive oxygen species (ROS) and plasma membrane lipid peroxidation (LPO) analysis. Mitochondrial functionality was assessed through the mitochondrial membrane potential (MMP). In the three examined species, a negative correlation emerged between sperm motility vs ROS levels and LPO. Sperm motility positively correlated with MMP in bovine, whereas these parameters were not related in ascidian or even negatively related in mussel sper- matozoa. MMP was negatively related to ROS and LPO levels in ascidians, only to LPO in bovine, Citation: Gallo, A.; Esposito, M.C.; and positively related in mussel spermatozoa. -
An Approach to the Factors Related to Sperm Capacitation Process
y: Open log A o cc r e d s n s A López-Úbeda and Matás Andrology 2015, 4:1 Andrology-Open Access http://dx.doi.org/10.4172/2167-0250.1000128 ISSN: 2167-0250 Research Article Open Access An Approach to the Factors Related to Sperm Capacitation Process Rebeca López-Úbeda and Carmen Matás* Department of Physiology, University of Murcia, Campus Mare Nostrum, 30071, Murcia, Spain Abstract This review summarizes some information about the different ways in relation to sperm capacitation. On one hand, the classical pathway that define the functional changes that occur in sperm during in vitro capacitation with special emphasis on the factors that lead to the tyrosine Phosphorylation (PY), and on the other hand, molecules and process that are involved in new mechanisms involved in this event like reactive species, especially Nitric Oxide (NO) and protein nitrosylation. Keywords: Spern capacitation; In vitro; Protein nitrosylation; Capacitation process implied several changes sequentially. Some of Phosphorylation these changes are rapid and occur at the moment of ejaculation. Others require a longer period of time in the female genital tract (in vivo) or Introduction in a medium capable of supporting this process (in vitro). All these After mating or artificial insemination, millions of sperm are processes (both rapid and slow), appear to be regulated by protein deposited in the female genital tract, of which only a small proportion is kinase A (PKA) and HCO-3, Soluble Adenylate Cyclase (SACY or able to reach the caudal portion of the isthmus (Figure 1A). This sperm sAC), and Cyclic Adenosine 3’5 ‘Monophosphate (cAMP) participate population encounters a sticky secretion of glycoprotein that modifies in this process (revised by [23]). -
Sperm Chemotaxis Is Driven by the Slope of the Chemoattractant
bioRxiv preprint doi: https://doi.org/10.1101/148650; this version posted June 10, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license . 1 Sperm chemotaxis is driven by the slope of the chemoattractant 2 concentration field 3 Ramírez-Gómez H.V.1, Jiménez-Sabinina V.2, Tuval I.3, Velázquez-Pérez M.1, Beltrán 4 C.1, Carneiro J.4, Wood C.D.1, 5, Darszon A.1, *, Guerrero A.1, 5, *. 5 1 Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de 6 Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, 7 Morelos, 62210, México. 8 2 Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 9 Heidelberg, Germany. 10 3 Mediterranean Institute for Advanced Studies, IMEDEA (CSIC-UIB), Esporles, 11 Balearic Islands, Spain. 12 4 Instituto Gulbenkian de Ciência (IGC), Rua da Quinta Grande, 6 2780-156, Oeiras, 13 Portugal. 14 5 Laboratorio Nacional de Microscopía Avanzada, Instituto de Biotecnología, 15 Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, 62210, 16 México. 17 * Correspondence and requests for materials should be addressed to A.G. or A.D. 18 (email: [email protected], [email protected]). 1 bioRxiv preprint doi: https://doi.org/10.1101/148650; this version posted June 10, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Cilia and Flagella of Eukaryotes
Cilia and Flagella of Eukaryotes I . R . GIBBONS The simple description that cilia are "contractile protoplasm in Early Developments its simplest form" (Dellinger, 1909) has fallen away as a mean- Among the most notable steps in the history of early studies ingless phrase ... A cilium is manifestly a highly complex and Downloaded from http://rupress.org/jcb/article-pdf/91/3/107s/1075481/107s.pdf by guest on 26 September 2021 compound organ, and . morphological description is clearly on cilia and flagella were the initial light microscope observa- only a beginning . tions of beating cilia on ciliated protozoa by Anton van Leeu- Irene Manton, 1952 wenhoek in 1675 ; the hypothesis proposed by W . Sharpey in 1835 that cilia and flagella are active organelles moved by contractile material distributed along their length rather than As recognized by Irene Manton (1) at the time that the basic passive structures moved by cytoplasmic flow or other contrac- 9 + 2 structural uniformity of cilia and most eukaryotic flagella tile activity within the cell body; and the observation in 1888- was first becoming recognized, these organelles are sufficiently 1890 by E . Ballowitz (2) that sperm flagella contain a substruc- complex that knowledge of their structure, no matter how ture of about 9-11 fine fibrils which are continuous along the detailed, cannot provide an understanding of their mechanisms length of the flagellum (Fig . 1) . More detailed accounts with of growth and function . In our understanding of these mecha- full references to this early work and to other studies before nisms, the substantial advances of the intervening 28 years 1948 can be found in the monographs of Sir James Gray (3) have, for the most part, resulted from experiments in which it and Michael Sleigh (4) . -
Sperm Chemotaxis Is Driven by the Slope of the Chemoattractant
RESEARCH ARTICLE Sperm chemotaxis is driven by the slope of the chemoattractant concentration field He´ ctor Vicente Ramı´rez-Go´ mez1, Vilma Jimenez Sabinina2, Martı´nVela´ zquez Pe´ rez1, Carmen Beltran1, Jorge Carneiro3, Christopher D Wood4, Idan Tuval5,6, Alberto Darszon1*, Ada´ n Guerrero4* 1Departamento de Gene´tica del Desarrollo y Fisiologı´a Molecular, Instituto de Biotecnologı´a, Universidad Nacional Auto´noma de Me´xico (UNAM), Cuernavaca, Mexico; 2Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; 3Instituto Gulbenkian de Cieˆncia (IGC), Rua da Quinta Grande, Oeiras, Portugal; 4Laboratorio Nacional de Microscopı´a Avanzada, Instituto de Biotecnologı´a, Universidad Nacional Auto´noma de Me´xico (UNAM), Cuernavaca, Mexico; 5Mediterranean Institute for Advanced Studies, IMEDEA (CSIC-UIB), Esporles, Spain; 6Department of Physics, University of the Balearic Islands, Palma, Spain Abstract Spermatozoa of marine invertebrates are attracted to their conspecific female gamete by diffusive molecules, called chemoattractants, released from the egg investments in a process known as chemotaxis. The information from the egg chemoattractant concentration field is 2+ 2+ decoded into intracellular Ca concentration ([Ca ]i) changes that regulate the internal motors that shape the flagellum as it beats. By studying sea urchin species-specific differences in sperm chemoattractant-receptor characteristics we show that receptor density constrains the steepness of the chemoattractant concentration gradient detectable by spermatozoa. Through analyzing *For correspondence: different chemoattractant gradient forms, we demonstrate for the first time that [email protected] (AD); Strongylocentrotus purpuratus sperm are chemotactic and this response is consistent with [email protected] (AG) frequency entrainment of two coupled physiological oscillators: i) the stimulus function and ii) the 2+ Competing interests: The [Ca ]i changes. -
Sperm Motility Index and Intrauterine Insemination Pregnancy Outcomes
Original Research Sperm Motility Index and Intrauterine Insemination Pregnancy Outcomes Chanel L. Bonds, MD; William E. Roudebush, PhD; and Bruce A. Lessey, MD, PhD From the Department of OB/GYN, Greenville Health System, Greenville, SC, (C.L.B., B.A.L.); De- partment of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC (W.E.R.); and Department of Surgery, Division of Urology, Greenville Health System, Greenville, SC (W.E.R.) Abstract Background: This study determined if sperm motility index affects pregnancy outcome following intrauterine insemination between various ovulation induction protocols. Methods: Calculated sperm motility (determined via computer-assisted semen analyzer) indices were correlated with pregnancy outcomes following intrauterine insemination. Results: Pregnancy rates for different ranges of sperm motility index values showed a trend of in- creasing pregnancy success across increasing ranges of grouped sperm motility index values, but none of these differences between groups was statistically significant. Within the clomid/letrozole cycles, male age differed significantlyP ( = .022) between the pregnant and non-pregnant groups. The difference in sperm motility index between pregnant and non-pregnant groups approached significance P( = .066). Conclusions: A trend exists for an increased pregnancy rate as the sperm motility index approaches 200. Furthermore, our research suggests that as the male partner becomes advanced in age, the chance for getting his partner pregnant declines significantly. ntrauterine insemination (IUI) has been a first- Published pregnancy rates following IUI reveal line treatment for many infertile couples since wide variation. A review article of 18 IUI studies Ithe early 1980s.1 In theory, IUI is successful in revealed a pregnancy rate that ranged from 5% to establishing pregnancy because the procedure 62%.