1,721,358 research outputs found
Unraveling the fertility knot in World Health Organization type 2 anovulatory women: another step toward a pharmacogenetic treatment choice
No full textFollicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility
Lessons Learned in Andrology: Back to the future: making children in bed (at the right time)
No full textComment on personal view of current status of male infertility diagnosis and treatmen
Mutations of the G protein-coupled receptors of the hypothalamo-pituitary-gonadal axis. Where do we stand?
No full textnot availabl
Transgenic animals in male reproductive research.
No full textAlthough transgenic mouse technology has already been widely used for the study of gene function and regulation in many areas of biomedicine, it has been applied only sporadically to the investigation of testicular function. Nevertheless, the contribution of this experimental approach to the understanding of male reproduction is considerable, not least because of the frequency of infertility in transgenic mice. Transgenic mice can be produced by microinjection of DNA constructs in the male pronucleus of fertilized eggs that are then retransferred into the oviducts of pseudopregnant females and allowed to develop to term. A proportion of the offspring have the foreign DNA sequences permamently integrated into the genome and thus become transgenic. In this way it is possible to obtain either the over-expression of genes, which can be targeted to the testis using testis-specific promoters, or to effect interruption of the functional integrity of genes by insertional mutagenesis. The regulation of gene expression in vivo can be studied by producing transgenic mice where the transgene is composed of the regulatory sequences of a gene of interest driving the expression of a reporter gene. Specific genes can be "knocked out" by homologous recombination. This article reviews the contribution of the transgenic approach to the following areas of male reproduction: the identification of factors involved in sex determination and development of the reproductive tract; the study of the function and expression of genes important for spermatogenesis and male reproduction; the identification of genes involved in spermatogenesis and of genomic sequences directing the expression of a transgene in the testis; the study of the function of specific reproductive tissues or cells in vivo; oncogenesis in reproductive tissues; the creation of cell lines suitable for in vitro studies; gene therapy
Molecular diagnosis of Y chromosome microdeletions in Europe: State-of-the-art and quality control
Full text linkThe polymerase chain reaction (PCR) screening of microdeletions of the Y chromosome has become an important diagnostic step in the work-up of male infertility. However, there is no agreement about how this diagnosis should be performed. There are suggestions that the large variation in deletion frequency reported in the literature could be due to the various selection criteria of the patients analysed, although methodological aspects may play a role as well. As for other genetic diseases, molecular diagnosis of Y chromosome microdeletions should be controlled by adopting strict internal quality control measures and by participating in external quality assessment schemes. Such an external quality assessment project is presently being organized jointly by the European Academy of Andrology and the European Molecular Genetics Quality Network. Three preliminary trials have given a state-of-the-art picture of the diagnostic performance in various European laboratories, showing an overall rate of misdiagnosis of ~5% for both AZFb and AZFc regions, and providing data useful in the generation of guidelines for the molecular diagnosis of Y chromosome microdeletions
Gonadotrophin Receptors
No full textThe two gonadotrophin receptors (GnRs), luteinizing hormone receptor (LHCGR) and follicle-stimulating receptor (FSHR), belong to the glycoprotein hormone receptor subgroup of type A G protein-coupled receptors (GPCRs). LHCGR binds specifically the two structurally similar gonadotrophins, luteinizing hormone (LH) and human chorionic gonadotrophin (hCG), and FSHR binds follicle-stimulating hormone (FSH). The receptors reside on plasma membrane and transmit the gonadotrophin signal to target cells using the classical Gs/adenylyl cyclase/cyclic AMP/protein kinase A signaling cascade. Other signaling pathways (e.g., inositol phosphate, calcium) are activated at pharmacological hormone concentrations or at high receptor density. LHCGR is expressed in testicular Leydig cells and in ovarian theca, luteinizing granulosa and luteal cells. FSHR is expressed in testicular Sertoli cells and ovarian granulosa cells. LHCGR activation stimulated Leydig cell steroidogenesis, in particular testosterone production, while FSHR maintains Sertoli cell metabolism, thereby indirectly stimulating spermatogenesis. Recent basic research, using GnR, expressing cells in vitro and genetically modified mice in vivo, has elucidated novel aspects of the molecular mechanisms of gonadotrophin receptor function. The crystal structure of GnRs has also been partly resolved. Numerous inactivating and activating GnR mutations that have been discovered in patients have unraveled the molecular basis of hypogonadism and other aberrations of reproductive endocrine functions. The purpose of this chapter is to review the recent trends of GnR research and how it has elucidated the molecular mechanisms of GnR function and the role of GnR in human reproductive physiology and pathophysiology
The EAA international quality control programme for Y-chromosomal microdeletions.
No full textnot availabl
Mechanisms in endocrinology: Genetics of FSH action: a 2014-and-beyond view
Full text linkOBJECTIVE: To assess the pharmacogenetic potential of FSH for infertility
treatment.
DESIGN: Review of the literature and genomic databases.
METHODS: Single-nucleotide polymorphism (SNP) assessed: rs6166 (c.2039A>G,
p.N680S), rs6165 (c.919A>G, p.T307A), rs1394205 (c.-29G>A) in FSHR, and
rs10835638 (c.-211G>T) in FSHB. Literature search via PubMed. Blast analysis of
genomic information available in the NCBI nucleotide database. Comparison of
allele frequency and haplotype distribution using the
http://spsmart.cesga.estool.
RESULTS: All these SNPs appear first in Homo, result in reduced FSH action, and
are present with variable frequencies and combinations worldwide. Stringent
clinical studies demonstrate that the FSHR genotype influences serum FSH levels
and gonadal response in both sexes. Serum FSH levels depend on the -211G>T SNP,
influencing transcriptional activity of the FSHB promoter. Genotypes reducing FSH
action are overrepresented in infertile subjects.
CONCLUSIONS: Although the clinical relevance of the FSHR polymorphisms alone is
limited, the combination of FSHR and FSHB genotypes has a much stronger impact
than either one alone in both sexes. About 20% of people are carriers of the
alleles associated with lower serum FSH levels/reduced FSHR expression or
activity, possibly less favorable for reproduction. Prospective studies need to
investigate whether stratification of infertile patients according to their
FSHR-FSHB genotypes improves clinical efficacy of FSH treatment compared with the
current, naïve approach. A relative enrichment of less favorable FSHR-FSHB
genotypes may be related to changes in human reproductive strategies and be a
marker of some health-related advantage at the cost of reduced fertility
Genetics of hypogonadotropic hypogonadism
No full textBackground: Idiopathic hypogonadotropic hypogonadism (HH) results from a defect in the normal pulsatile secretion pattern of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Clinically it can be categorized as one of two types: HH associated with anosmia, known as Kallmann syndrome, and isolated HH. The anatomical explanation for Kallmann syndrome stems from incomplete or total failure of GnRH-secreting neurons to migrate from the olfactory epithelium to their final destination in the mediobasal hypothalamus. Several genes are involved in the migration of the GnRH neurons. Conclusions: Mutations of the KAL1 gene, encoding for anosmin 1, and of the FGFR1 (or KAL2) gene, encoding for fibroblast growth factor receptor 1, can be found in familial cases of Kallmann syndrome. KAL1 mutations are responsible for X-linked recessive inheritance, and FGFR1 mutations are the autosomal dominant form. Moreover, mutations of the gonadotropin-releasing hormone receptor gene and G-protein-coupled receptor 54 gene are found in over 50% of familial cases of isolated HH with autosomal recessive inheritance
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