Cyclic FEE peptide increases human gamete fusion and potentiates its RGD-induced inhibition

Ziyyat, Ahmed; Naud-Barriant, Nathalie; Barraud-Lange, Virginie; Chevalier, Fabien Le; Kulski, O.; Lemkecher, T.; Bomsel, Morgane; Wolf, Jean-Philippe

doi:10.1093/humrep/dei241

Cited by 15 publications

(24 citation statements)

References 66 publications

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“…Overnight insemination is the standard incubation time condition for human eggs (Tournaye et al, 1997;Ziyyat et al, 2005;Barraud-Lange et al, 2008). For analysis, oocytes were washed and loaded with the DNA-specific fluorochrome Hoechst 33342 (Sigma-Aldrich) at 5 μg/ml for 5 min.…”

Section: Fusion Assaymentioning

confidence: 99%

Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization

et al. 2014

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Little is known about the molecular mechanisms that induce gamete fusion during mammalian fertilization. After initial contact, adhesion between gametes only leads to fusion in the presence of three membrane proteins that are necessary, but insufficient, for fusion: Izumo1 on sperm, its receptor Juno on egg and Cd9 on egg. What happens during this adhesion phase is a crucial issue. Here, we demonstrate that the intercellular adhesion that Izumo1 creates with Juno is conserved in mouse and human eggs. We show that, along with Izumo1, egg Cd9 concomitantly accumulates in the adhesion area. Without egg Cd9, the recruitment kinetics of Izumo1 are accelerated. Our results suggest that this process is conserved across species, as the adhesion partners, Izumo1 and its receptor, are interchangeable between mouse and human. Our findings suggest that Cd9 is a partner of Juno, and these discoveries allow us to propose a new model of the molecular mechanisms leading to gamete fusion, in which the adhesion-induced membrane organization assembles all key players of the fusion machinery.

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Section: Fusion Assaymentioning

confidence: 99%

Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization

et al. 2014

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“…In conclusion, we previously showed that cyclic FEE peptide binds to the human oocyte membrane (24), most probably on the a6b1 integrin. This integrin is present on human oocytes and sperm.…”

Section: Number Of Littersmentioning

confidence: 59%

“…But as we have already shown with the human equivalent of QDE (cFEE), it is probably both the peptide composition and cyclization that might explain our results (24). Indeed, our peptide does not contain a terminal aspartic acid, which has been shown to be responsible for the inhibitory effect (26).…”

Section: Number Of Littersmentioning

confidence: 61%

“…It has been shown that linear CAQDEC reduces sperm binding and sperm-egg fusion but the cyclic form did not have any inhibitory effect on zona-free oocytes, which suggests different properties for different peptide conformations (27). This result may be species dependent; Myles et al (14) found that an equivalent cyclic peptide was an inhibitor in the guinea pig whereas cFEE enhanced gamete fusion on human zonafree oocytes (24).…”

Section: Number Of Littersmentioning

confidence: 99%

“…This cyclic form mimics the effect of the sperm interaction on the egg. Indeed, we showed that the cyclic peptide (CSFEEC) mimicking the ADAM2 disintegrin-binding domain increases the fertilization index of human zona pellucida (ZP)-free oocyte (24).…”

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confidence: 99%

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Cyclic QDE peptide increases fertilization rates and provides healthy pups in mouse

Barraud-Lange¹,

Naud-Barriant²,

Ducot

et al. 2009

Fertility and Sterility

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Role of sperm αvβ3 integrin in mouse fertilization

Boissonnas

Montjean

Lesaffre

et al. 2010

Developmental Dynamics

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Oocyte integrins have been described as essential for fertilization. But this concept has been challenged by deletion experiments. Recently, we have shown that sperm integrin a6b1 plays a determinant role in mouse gamete interaction. In this study, we demonstrate the presence of avb3 integrin by Western blot and immunofluorescence on the sperm membrane. Oocytes and/or sperm preincubations with anti-av or anti-b3 antibodies were performed before in vitro fertilization on cumulus-intact and zona-free egg assays. We observed inhibitory effects on the fusion process mostly by means of sperm function. An antibody directed against vitronectin inhibited gametes fusion, whereas the presence of exogenous vitronectin increased its efficiency. We suggest that vitronectin (on multimeric forms) can play a first nonspecific link corresponding to loosely bound spermatozoa to oocyte and that this link could be mediated by means of oocyte proteoglycans or integrins, and sperm avb3 integrin. Developmental Dynamics 239:773-783,

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Cyclic FEE peptide increases human gamete fusion and potentiates its RGD-induced inhibition

Abstract: RGD-sensitive and -insensitive integrins may be associated in a multimolecular complex working as a sperm receptor on the human oocyte membrane. Supplementation of human IVF culture medium with cFEE peptide might improve fertilization rates in ART.

Cited by 15 publications

References 66 publications

Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization

Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization

Cyclic QDE peptide increases fertilization rates and provides healthy pups in mouse

Role of sperm αvβ3 integrin in mouse fertilization

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