1,721,290 research outputs found

    The INSL3-LGR8 hormonal system in humans: Testicular descent, cryptorchidism and testicular functions

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    INSL3 is a member of the relaxin-insulin family, and it is expressed in pre- and postnatal Leydig cells of the testis in a variety of mammalian species, including humans. This peptide affects testicular descent during embryonic development by acting on gubernaculum via its specific receptor LGR8. From initial animal data showing the cryptorchid phenotype of Insl3/Lgr8 mutants, an extensive search for mutations in the INSL3 and LGR8 genes was undertaken in human patients with cryptorchidism. Six mutations in INSL3 and one in LGR8 genes have been detected exclusively in men with undescended testes, with an overall frequency of mutation in cryptorchid or ex-cryptorchid men of 4-5%. Definitive proofs of a causative role for many of these mutations are still lacking. However, the specific association with cryptorchidism actually suggests that they might be responsible for the phenotype. Apart from the role in testicular descent and cryptorchidism, more recent data suggest additional yet unidentified endocrine and paracrine actions in adults. INSL3 is produced constitutively, but in a differentiation-dependent manner by the adult Leydig cells, and its production and secretion is dependent on LH. INSL3 circulates at high concentrations in serum of adult males and it is increasingly used as a specific marker of Leydig cell differentiation and function. Research is needed to clarify the possible paracrine role of the INSL3/LGR8 system in the testis and ovary, and endocrine effects in many tissues where LGR8 expression has been identified. © 2005 Bentham Science Publishers Ltd

    mechanism of human sperm activation by extracellular atp

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    We have identified the mechanism whereby extracellular ATP (ATPe) triggers the acrosome reaction in human spermatozoa. This nucleotide opens a ligand-gated ion channel expressed on the sperm plasma membrane. ATPe threshold and 50% effective concentration calculated on the total added ATPe are 0.1 and 2 mM, respectively, corresponding to a free ATP concentration (ATP4-) of 3 and 200 microM, respectively. The ATPe-gated channel is selective for monovalent cations (Na+, choline, and methylglucamine), whereas on the contrary, permeability to Ca2+ is negligible. Isosmolar replacement of extracellular Na+ with sucrose fully blocked ATPe-dependent sperm activation, thus suggesting a mandatory role for Na+ influx. These results show that human sperm express an ATPe-gated Na+ channel that might have an important role in sperm activation before egg fertilization

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Impact of Endocrine Disruptors on Male Sexual Development

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    Many andrological pathologies seen in adults, including infertility, actually arose in younger age, due to the strong susceptibility and vulnerability of male gonads to external insults, starting from gestational age and during all growth phases. Three main phases are particularly susceptible for normal testis development and function: the intrauterine phase, the neonatal phase comprising the so-called minipuberty, and puberty. However, even during infancy, when the testes are apparently “sleeping,” damaging causes with permanent effects on testicular function can occur. Among risk factors for alterations of sexual and reproductive organs and function, endocrine-disrupting chemicals (EDCs) have gained particular attention in the last decades, given their ability to disrupt them at different levels and at different ages, with long-term consequences and possibly also transgenerational effects. Bisphenol A, phthalates, and perfluoroalkyl substances are particularly intriguing chemicals, given the strong experimental evidence suggesting effects on hormone nuclear receptors, hypothalamus-pituitary-testis axis, and direct action on spermatogenesis and steroidogenesis. Although epidemiological studies in humans have shown controversial and inconsistent results, the overall conclusion points toward a positive association between exposure to EDCs and alteration of male reproductive system
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