The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Anil Suri - One of the best experts on this subject based on the ideXlab platform.
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Contraceptive vaccines targeting sperm.
Expert opinion on biological therapy, 2005Co-Authors: Anil SuriAbstract:Overpopulation is a global problem of significant magnitude, with grave implications for the future. Development of new contraceptives is necessary, as existing forms of birth Control are unavailable, impractical and/or too expensive for many individuals due to sociological, financial or educational limitations. Immunocontraception and, in particular, the targeting of antibodies to sperm-specific antigens implicated in sperm-egg binding and fertilisation offers an attractive approach to Control Fertility. Sperm-specific antibodies may impair Fertility by inhibiting sperm motility, by reducing penetration of the cervical mucus by sperm, or by interfering in sperm capacitation or the acrosome reaction; alternatively, antisperm antibodies may invoke the complement cascade, resulting in sperm lysis. The antibodies raised against sperm-specific antigens have proved to be extremely effective at reducing sperm-egg interactions in vitro; Fertility trials in subhuman primates will eventually be needed to prove the effectiveness of the sperm antigens in terms of contraceptive efficacy before trials in humans can be justified. In addition, existing and emerging strategies (such as sperm proteomics, the determination of molecular and structural details of sperm proteins, and the modelling of protein-ligand interactions using X-ray and/or NMR structures to name a few) are expected to provide the experimental foundation for the design of small molecule inhibitors with antiFertility effects. The technology underpinning vaccine development is constantly being developed and the introduction of DNA/RNA vaccines is certain to impact upon the field of immunocontraception.
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sperm specific proteins potential candidate molecules for Fertility Control
Reproductive Biology and Endocrinology, 2004Co-Authors: Anil SuriAbstract:The increase in population growth rate warrants the development of additional contraceptive methods that are widely acceptable, free from side effects and less expensive. Immunocontraception, and in particular the targeting of antibodies to gamete-specific antigens implicated in sperm egg binding and fertilization, offers an attractive approach to Control Fertility. The development of a contraceptive vaccine based on sperm antigen represents a promising approach to contraception. In mammals, fertilization is completed by the direct interaction of sperm and egg, a process mediated primarily by sperm surface proteins. Sperm have proteins that are unique, cell specific, immunogenic and accessible to antibodies. A few of the sperm specific proteins have been isolated and characterized. The antibodies raised against the sperm specific antigens have proved to be extremely effective at reducing sperm-egg interaction in vitro; Fertility trials in sub-human primates would eventually prove the effectiveness of the sperm antigens in terms of contraceptive efficacy.
Sarah Gallet - One of the best experts on this subject based on the ideXlab platform.
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Brain Endothelial Cells Control Fertility through Ovarian-Steroid–Dependent Release of Semaphorin 3A
PLoS Biology, 2014Co-Authors: Paolo Giacobini, Jyoti Parkash, Celine Campagne, Andrea Messina, Filippo Casoni, Charlotte Vanacker, Fanny Langlet, Barbara Hobo, Gabriella Cagnoni, Sarah GalletAbstract:Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide Controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus Controlling key physiological functions such as reproduction.
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brain endothelial cells Control Fertility through ovarian steroid dependent release of semaphorin 3a
PLOS Biology, 2014Co-Authors: Paolo Giacobini, Jyoti Parkash, Celine Campagne, Andrea Messina, Filippo Casoni, Charlotte Vanacker, Fanny Langlet, Barbara Hobo, Gabriella Cagnoni, Sarah GalletAbstract:Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide Controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus Controlling key physiological functions such as reproduction.
Paolo Giacobini - One of the best experts on this subject based on the ideXlab platform.
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Brain Endothelial Cells Control Fertility through Ovarian-Steroid–Dependent Release of Semaphorin 3A
PLoS Biology, 2014Co-Authors: Paolo Giacobini, Jyoti Parkash, Celine Campagne, Andrea Messina, Filippo Casoni, Charlotte Vanacker, Fanny Langlet, Barbara Hobo, Gabriella Cagnoni, Sarah GalletAbstract:Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide Controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus Controlling key physiological functions such as reproduction.
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brain endothelial cells Control Fertility through ovarian steroid dependent release of semaphorin 3a
PLOS Biology, 2014Co-Authors: Paolo Giacobini, Jyoti Parkash, Celine Campagne, Andrea Messina, Filippo Casoni, Charlotte Vanacker, Fanny Langlet, Barbara Hobo, Gabriella Cagnoni, Sarah GalletAbstract:Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide Controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus Controlling key physiological functions such as reproduction.
Alan Richard Clarke - One of the best experts on this subject based on the ideXlab platform.
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apc2 is critical for ovarian wnt signalling Control Fertility and tumour suppression
BMC Cancer, 2019Co-Authors: Nohaehssan Mohamed, Trevor Hay, Karen Ruth Reed, Matthew John Smalley, Alan Richard ClarkeAbstract:Canonical WNT signalling plays a critical role in the regulation of ovarian development; mis-regulation of this key pathway in the adult ovary is associated with subFertility and tumourigenesis. The roles of Adenomatous polyposis coli 2 (APC2), a little-studied WNT signalling pathway regulator, in ovarian homeostasis, Fertility and tumourigenesis have not previously been explored. Here, we demonstrate essential roles of APC2 in regulating ovarian WNT signalling and ovarian homeostasis. A detailed analysis of ovarian histology, gene expression, ovulation and hormone levels was carried out in 10 week old and in aged constitutive APC2-knockout (Apc2−/−) mice (mixed background). Statistical significance for qRT-PCR data was determined from 95% confidence intervals. Significance testing was performed using 2-tailed Student’s t-test, when 2 experimental cohorts were compared. When more were compared, ANOVA test was used, followed by a post-hoc test (LSD or Games-Howell). P-values of < 0.05 were considered statistically significant. APC2-deficiency resulted in activation of ovarian WNT signalling and sub-Fertility driven by intra-ovarian defects. Follicular growth was perturbed, resulting in a reduced rate of ovulation and corpora lutea formation, which could not be rescued by administration of gonadotrophins. Defects in steroidogenesis and follicular vascularity contributed to the subFertility phenotype. Tumour incidence was assessed in aged APC2-deficient mice, which also carried a hypomorphic Apc allele. APC2-deficiency in these mice resulted in predisposition to granulosa cell tumour (GCT) formation, accompanied by acute tumour-associated WNT-signalling activation and a histologic pattern and molecular signature seen in human adult GCTs. Our work adds APC2 to the growing list of WNT-signalling members that regulate ovarian homeostasis, Fertility and suppress GCT formation. Importantly, given that the APC2-deficient mouse develops tumours that recapitulate the molecular signature and histological features of human adult GCTs, this mouse has excellent potential as a pre-clinical model to study ovarian subFertility and transitioning to GCT, tumour biology and for therapeutic testing.
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APC2 is critical for ovarian WNT signalling Control, Fertility and tumour suppression
BMC cancer, 2019Co-Authors: Nohaehssan Mohamed, Trevor Hay, Karen Ruth Reed, Matthew John Smalley, Alan Richard ClarkeAbstract:Canonical WNT signalling plays a critical role in the regulation of ovarian development; mis-regulation of this key pathway in the adult ovary is associated with subFertility and tumourigenesis. The roles of Adenomatous polyposis coli 2 (APC2), a little-studied WNT signalling pathway regulator, in ovarian homeostasis, Fertility and tumourigenesis have not previously been explored. Here, we demonstrate essential roles of APC2 in regulating ovarian WNT signalling and ovarian homeostasis. A detailed analysis of ovarian histology, gene expression, ovulation and hormone levels was carried out in 10 week old and in aged constitutive APC2-knockout (Apc2−/−) mice (mixed background). Statistical significance for qRT-PCR data was determined from 95% confidence intervals. Significance testing was performed using 2-tailed Student’s t-test, when 2 experimental cohorts were compared. When more were compared, ANOVA test was used, followed by a post-hoc test (LSD or Games-Howell). P-values of
Charlotte Vanacker - One of the best experts on this subject based on the ideXlab platform.
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Brain Endothelial Cells Control Fertility through Ovarian-Steroid–Dependent Release of Semaphorin 3A
PLoS Biology, 2014Co-Authors: Paolo Giacobini, Jyoti Parkash, Celine Campagne, Andrea Messina, Filippo Casoni, Charlotte Vanacker, Fanny Langlet, Barbara Hobo, Gabriella Cagnoni, Sarah GalletAbstract:Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide Controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus Controlling key physiological functions such as reproduction.
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brain endothelial cells Control Fertility through ovarian steroid dependent release of semaphorin 3a
PLOS Biology, 2014Co-Authors: Paolo Giacobini, Jyoti Parkash, Celine Campagne, Andrea Messina, Filippo Casoni, Charlotte Vanacker, Fanny Langlet, Barbara Hobo, Gabriella Cagnoni, Sarah GalletAbstract:Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide Controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus Controlling key physiological functions such as reproduction.