Abstract:
STUDY QUESTION:Is it possible to identify original compounds that are able to enhance sperm motility from the venom of the scorpion Scorpio maurus palmatus? SUMMARY ANSWER:We identified a potent disulfide-rich peptide (DRP) of 73 amino acids that significantly improved the motility of fresh and frozen-thawed sperm in different mammalian species, including human, and improved fertilization outcome in mouse IVF experiments. WHAT IS KNOWN ALREADY:Any disturbance of sperm motility has a strong impact on fertilization and can lead to subfertility or infertility. Significant efforts have, therefore, been made to identify pharmacological drugs that might improve sperm motility. Such compounds are particularly useful in azoospermia to improve testicular sperm extraction and in the domain of cryopreservation because the motility of frozen-thawed sperm is reduced. STUDY DESIGN, SIZE, DURATION:This was a basic science/medical research study aimed at identifying original compounds from a library of venoms able to enhance mammalian sperm motility, including human. We first identified in the venom of a scorpion S. m. palmatus a fraction able to potently activate sperm motility. We next purified and characterized the compound by liquid chromatography, mass spectrometry and peptide synthesis. Finally, the potency and toxicity of both purified and synthetic versions of the identified compound on sperm motility were assessed using different in vitro tests in different mammalian species. PARTICIPANTS/MATERIALS, SETTING, METHODS:For human sperm, biological samples were collected from normozoospermic donors and subfertile patients attending a reproduction department for diagnostic semen analysis. Testicular sperm was collected from cynomolgus monkeys (Macaca fascicularis) euthanized for the needs of specific authorized research projects. The peptide was also tested on bovine and mouse epidydimal sperm. We measured different sperm motility parameters with a computer-assisted sperm analysis system in the presence or absence of the peptide. MAIN RESULTS AND THE ROLE OF CHANCE:Size exclusion chromatography enabled us to isolate a fraction of the venom of S. m. palmatus able to increase sperm motility. By liquid chromatography and mass spectrometry, a peptide comprising 73 amino acids with 4 disulfide bridges was identified as responsible for the biological activity and called 'spermaurin'. The identity of spermaurin was confirmed by chemical synthesis. We showed that the peptide increased the motility of fresh and frozen-thawed human sperm. We observed that the potency of the peptide was higher on fresh ejaculated spermatozoa with a low motility, achieving a 100% increase of curvilinear velocity in poorly performing sperm. We also demonstrated that peptide is effective on bovine and mouse fresh epididymal, bovine frozen-thawed ejaculated and fresh non-human primate testicular sperm. Finally, in mouse IVF, the production of 2-cell embryos was increased by 24% when sperm were treated with the peptide. LIMITATIONS, REASONS FOR CAUTION:This work is an in vitro evaluation of the ability of spermaurin to improve sperm motility parameters. Another limitation of this study is the small number of human sperm samples tested with the natural (n = 36) and synthetic (n = 12) peptides. Moreover, the effect of the peptide on IVF outcome was only tested in mouse and further tests with human and bovine gametes are required to confirm and extend this result in other mammalian species. WIDER IMPLICATIONS OF THE FINDINGS:This work confirms our initial study showing that venoms represent an interesting source of molecules that are able to modify sperm physiology. Moreover, this work presents the first demonstrated biological action of a venom peptide from the scorpion S. m. palmatus with sequence similarities to La1 peptide from Liocheles australasiae (Wood scorpion), a widespread family of DRPs. LARGE SCALE DATA:Not applicable. STUDY FUNDING/COMPETING INTEREST(S):This work is part of the project 'LAB COM-14 LAB7 0004 01-LIPAV', funded by the program LabCom 2014 from the French Research Agency (ANR). Dr Arnoult reports grants from IMV Technologies during the conduct of the study. In addition, Drs Arnoult, Martinez, Ray and Schmitt have a patent EP16305642.7 pending containing some of the information presented in this manuscript.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Martinez G,Hograindleur JP,Voisin S,Abi Nahed R,Abd El Aziz TM,Escoffier J,Bessonnat J,Fovet CM,De Waard M,Hennebicq S,Aucagne V,Ray PF,Schmitt E,Bulet P,Arnoult Cdoi
10.1093/molehr/gaw075subject
Has Abstractpub_date
2017-02-10 00:00:00pages
116-131issue
2eissn
1360-9947issn
1460-2407pii
gaw075journal_volume
23pub_type
杂志文章abstract::The objectives of this study were to determine if human ejaculated sperm exhibit active caspases and if caspase-dependent apoptosis markers are identifiable. Sperm from fertile donors and infertile patients were examined after gradient separation into leukocyte-free fractions of high and low motility. Sperm were evalu...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.11.984
更新日期:2002-11-01 00:00:00
abstract::Recurrent pregnancy loss (RPL) is a common and distressing disorder. Chromosomal errors in the embryo are the single most common cause, whereas uterine factors are invariably invoked to explain non-chromosomal miscarriages. These uterine factors are, however, poorly defined. The ability of a conceptus to implant in th...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gaq079
更新日期:2010-12-01 00:00:00
abstract::The influence of seminal plasma on the mRNA expression of cytokines in human endometrial epithelial and stromal cells and the cytokine production of spermatozoa were investigated in vitro. Seminal plasma and spermatozoa were collected from healthy volunteers and were screened by enzyme-linked immunosorbent assay for c...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag095
更新日期:2003-12-01 00:00:00
abstract:STUDY QUESTION:Do human adult Leydig cells (ALCs) within hyperplastic micronodules display characteristics of foetal LCs (FLCs)? SUMMARY ANSWER:The gene expression profiles of FLCs and all ALC subgroups were clearly different, but there were no significant differences in expressed genes between the normally clustered ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax012
更新日期:2017-05-01 00:00:00
abstract::Tenascin-C is an extracellular matrix glycoprotein whose monomers include eight consecutive fibronectin type III-like repeats, encoded by exons 10-16, and which are subject to alternative splicing. Transcripts containing these exons are expressed during tissue wounding and active tissue remodelling. Human fetal membra...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.11.1066
更新日期:1999-11-01 00:00:00
abstract::We describe a rapid and specific differential amplification system which can detect five of the most common cystic fibrosis mutations from a single cell. In the first round of the polymerase chain reaction (PCR), regions of exons 4, 10 and 11 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene conta...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.3.203
更新日期:1996-03-01 00:00:00
abstract::Villous tissues from 30 spontaneous abortions and the same number of artificial abortions were obtained and analysed for the frequency of polyploid cells. Single cell suspensions were made from these tissues without culture and the ploidy of > 100 cells was analysed. Trisomies of chromosomes 17 and 4 have rarely been ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.5.445
更新日期:1997-05-01 00:00:00
abstract::Several investigators have noted that hormone-dependent development of endometriosis implants lags behind that of simultaneously analysed eutopic endometrium. With the recent discovery of the oestrogen receptor-beta (ER-beta) isoform, the aim of this study was to investigate whether differences in the expression of ER...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.7.651
更新日期:1999-07-01 00:00:00
abstract::Previous studies have implicated receptor tyrosine kinases in progesterone-induced [Ca2+]i signalling, and consequent induction of the acrosome reaction, in human spermatozoa. We have investigated the effects of tyrosine kinase inhibition on [Ca2+]i responses in large numbers of individual human spermatozoa. Genistein...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.4.326
更新日期:2002-04-01 00:00:00
abstract::The distribution and size of a surface membrane antigen identified by a monoclonal antibody (MAC9393) have been examined in testicular and epididymal bovine sperm preparations. Western blots indicated a substantial decrease in molecular mass of the antigen during epididymal maturation from approximately 87 kDa in the ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.7.673
更新日期:1998-07-01 00:00:00
abstract::Sperm experience intense and varied selection that dramatically impacts the evolution of sperm quality. Selection acts to ensure that sperm are fertilization-competent and able to overcome the many challenges experienced on their way towards eggs. However, simply being able to fertilize an egg is not enough to ensure ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gau067
更新日期:2014-12-01 00:00:00
abstract::Fatty acid amide hydrolase (FAAH) is involved in embryo development and implantation. Sex hormones down-modulate FAAH activity in the mouse uterus. However, the regulation of the FAAH gene in the uterus is unknown. Our results showed that FAAH mRNA is localized to uterine epithelial cells and circular myometrium durin...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/8.7.651
更新日期:2002-07-01 00:00:00
abstract::Oocytes are usually the largest cells in the body and as such offer unique opportunities for single-cell analysis. Unfortunately, these cells are also some of the rarest in the mammalian female, usually necessitating single-cell analysis. In cases of infertility in humans, determining the quality of the oocyte is ofte...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gav064
更新日期:2016-03-01 00:00:00
abstract::The peri-implantation period is a critical time during murine development. Although the importance of nitric oxide has been demonstrated during gestation, its role in implantation has not been fully defined. The aim of this study was to quantify (by Western blotting) two prominent nitric oxide synthase (NOS) isoforms,...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.5.467
更新日期:1999-05-01 00:00:00
abstract::Charcot-Marie-Tooth (CMT) disease is the 'common' name for a range of hereditary peripheral neuropathies. CMT1 is the most common form and is transmitted in an autosomal dominant manner. CMT1A maps to chromosome 17p11.2 and is caused, in the majority of cases, by a 1.5 Mb DNA duplication, that includes the peripheral ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag054
更新日期:2003-07-01 00:00:00
abstract:Study Question:Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)? Summary Answer:E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs. What is Known Alre...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax006
更新日期:2017-03-01 00:00:00
abstract::Idiopathic fetal growth restriction (FGR) is often associated with placental insufficiency. Previously, we isolated and characterized homeobox gene DLX4 from the placenta and provided evidence that DLX4 may regulate placental development. Here, we have investigated whether DLX4 expression levels were altered in idiopa...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gal087
更新日期:2006-12-01 00:00:00
abstract::A number of placental cytokines participate in the feto-maternal defence mechanism. Monocyte chemotactic and activating factor (MCAF) is one of these chemokines. We investigated the pattern of placental MCAF production, the localization of MCAF-producing cells in the placenta, and alterations in its expression in chor...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.4.393
更新日期:1998-04-01 00:00:00
abstract:STUDY HYPOTHESIS:In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. STUDY FINDING:We demonstrate mechanistic differences between preterm birt...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav074
更新日期:2016-02-01 00:00:00
abstract::Successful pregnancy in humans depends on deep invasion of the maternal decidua by extravillous trophoblast cells (EVTs), a process regulated by autocrine and paracrine signals in the decidual-trophoblast microenvironment. Here we examined whether trophoblast invasion is affected by decidual differentiation of endomet...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gar015
更新日期:2011-07-01 00:00:00
abstract::The androgen receptor (AR) gene is located on the X chromosome and contains a polymorphic CAG tract. CAG repeat expansions in the AR have been associated with male infertility and the neuromuscular disease, spinal bulbar muscular atrophy (SBMA). Based on Mendelian inheritance patterns, moderate CAG expansions in infer...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.9.861
更新日期:2000-09-01 00:00:00
abstract::The major regulators of endometrial function are oestrogen and progesterone, which act through binding their nuclear receptors and by activating transcription of their target genes. Interactions between steroid receptors and transcription proteins, e.g. c-JUN/AP-1, can modulate steroid action at the transcriptional le...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/4.12.1110
更新日期:1998-12-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gax063
更新日期:2018-02-01 00:00:00
abstract::This study was initiated to determine the relationship between the fertilizing potential of spermatozoa and abnormalities in the compact packing of their chromatin which occurs in the final stage of male germ cell differentiation. Chromatin packing involves disulphide bridge covalent cross-linking. The degree of packi...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.9.825
更新日期:1999-09-01 00:00:00
abstract::The Drosophila melanogaster staufen gene encodes an RNA binding protein (Dm Stau) required for the localization and translational repression of mRNAs within the Drosophila oocyte. In mammals translational repression is important for normal spermatogenesis in males and storage of mRNAs in the oocytes of females. In the...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/6.11.983
更新日期:2000-11-01 00:00:00
abstract::Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine ...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav028
更新日期:2015-08-01 00:00:00
abstract::Oxidative damage by reactive oxygen species (ROS) is a major cause of sperm dysfunction. Excessive ROS generation reduces fertilization and enhances DNA damage of spermatozoa. Interaction between spermatozoa and oviductal epithelial cells improves the fertilizing ability of and reduces chromatin damage in spermatozoa....
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gav015
更新日期:2015-06-01 00:00:00
abstract::Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes known as the nitric oxide synthases (NOS). We have recently shown a NOS similar to constitutive brain NOS (bNOS) and endothelial NOS (ecNOS) to be present in spermatozoa. The aim of this study is to investigate NO production by human spermatozoa a...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.9.755
更新日期:1997-09-01 00:00:00
abstract::Because of its distinctive ability to act as a mitogen, a mitogen and a morphogen, hepatocyte growth factor/scatter factor (HGF/SF) has all the characteristics of a molecule able to function in regulatory networks of motility, such as the spermatogenic epithelium, and this through binding of its receptor p190MET (C-ME...
journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/2.1.2
更新日期:1996-01-01 00:00:00
abstract::In Europe up to one in four couples experience difficulty conceiving and in half of these cases the problem has been attributed to sub or infertility in the male partner. The development of assisted reproductive technologies (ART) such as in vitro fertilization and intra-cytoplasmic spermatozoa injection has allowed s...
journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/gam089
更新日期:2008-01-01 00:00:00