Elsa de la Chesnaye

No evidence of mutations in the follicle-stimulating hormone receptor gene in Mexican women with 46,XX pure gonadal dysgenesis

In the ovary FSH is necessary for normal follicular development, binding to its receptor (FSHR) that pertains to the superfamily of G-protein coupled receptors. In the FSHR gene, which consists of 10 exons, an homozygous mutation was reported in six Finnish families with gonadal dysgenesis; whereas two isolated French patients exhibited compound heterozygous mutations. Several groups, however, have searched for FSHR mutations, although in most cases the gene has been studied partially, not finding any genetic abnormalities in German, English, North American or Brazilian women. We performed direct sequencing of all 10 exons of the FSHR gene in seven sporadic patients and two sisters with 46,XX pure gonadal dysgenesis, to investigate the cause of their disorder. No heterozygous or homozygous mutant alleles were present in any of the patients. Although the number of patients evaluated was small, considering all the other previous reports, it seems that except in the Finnish population, the proportion of women with mutations in the encoding region of this gene is very low. Other possibilities for the presence of 46,XX gonadal dysgenesis, such as defects in the regulatory regions of the FSHR gene promoter, in the untranslated regions of exons 1 and 10, and within introns, or the existence of other genes likely to be important for normal ovarian function on the X chromosome or on autosomes, should be considered. In contrast with other studies, we did not find polymorphisms of the FSHR gene, indicating that apparently in Mexicans this gene is not highly polymorphic.

Analysis of C-850T and G-308A Polymorphisms of the Tumor Necrosis Factor-α Gene in Maya-Mestizo Women with Preeclampsia

Objective: To determine whether polymorphisms in the TNF-α promoter gene are associated with preeclampsia. Methods: 105 women with preeclampsia and 200 controls were genotyped for the G-308A and C-850T polymorphisms by RFLP. Differences in allele, genotype, and haplotype frequencies between groups were assessed. Results: The genotypic and allelic distribution of both polymorphisms was similar between groups. Moreover, the estimated overall pair of loci haplotype frequencies did not differ significantly. Conclusion: We did not find any association between these polymorphisms and the risk for preeclampsia. However, we found that both the genotypic and allelic distribution in our population differed from those reported in other populations.

Fbxw15/Fbxo12J Is an F-Box Protein-Encoding Gene Selectively Expressed in Oocytes of the Mouse Ovary

Abstract In recent years, several factors required for follicular assembly and/or early growth of newly formed primordial follicles have been characterized, but additional factors likely remain to be identified. We have used cDNA arrays to compare gene expression in the neonatal mouse ovary at 48 h (when primordial follicles are being assembled) and at 96 h (when early follicular growth is taking place) after birth to that of ovaries collected <24 h after birth (when follicles have not yet been formed). Segregating genes according to their pattern of expression revealed the presence of one cluster of 24 genes for which expression consistently increased at 48 and 96 h. The top increaser in this cluster encodes a ∼1.5-kb mRNA containing an open reading frame of 1401 bp that encodes a protein of 466 amino acids. The predicted 52.3-kDa protein is a member of the F-box-only (FBXO) protein family, termed FBXW15 or FBXO12J. It has a cytoplasmic localization that includes the endoplasmic reticulum. Expression of Fbxw15/Fbxp12J mRNA is oocyte-specific; the mRNA is first detected on Gestational Day 18, decreasing thereafter to minimal levels on the day of birth. The prevalence of Fbxw15/Fbxp12J mRNA increases again at 48 and 96 h after birth, coinciding with the time of follicular assembly and the initiation of early follicular growth, respectively. The specific expression of Fbxw15/Fbxp12J in oocytes and its developmental pattern of expression suggest a role for this gene in the regulation of oocyte physiology.

The transcription factors Sox5 and Sox9 regulate Catsper1 gene expression

Catsper is a Ca2+permeable channel required for sperm hyperactivation. In spite of its central role in male fertility, the transcriptional mechanisms that regulate Catsper1 expression are ill defined. In this work, we describe the identification and characterization of important regulatory elements in the murine Catsper1 gene proximal promoter. Four transcription start sites and three functional Sox‐binding sites were identified in the Catsper1 promoter. Interestingly, transcription factors Sox5 and Sox9 caused a significant increase in transactivation of the Catsper1 promoter in heterologous systems, and chromatin immunoprecipitation assays showed that both transcription factors interact with the Catsper1 promoter in vivo. These results provide new insights into the molecular mechanisms that control Catsper channel expression.

Scant XYqh− testicular cells with normal SRY was enough to differentiate bilateral testes in a 45,X/46,XYqh− patient

OBJECTIVE It has been established that in 45,X/46,XY individuals predominance of XY or XO gonadal cells determines gonadal differentiation. However, in some cases there is no concordance between the predominance of XY cells and testis differentiation. Here we describe the SRY findings in a patient bearing a 45,X/46,XYqh- karyotype. STUDY DESIGN The patient presented two small testes (one with spermatogenesis), a male phenotype, and a predominant 45,X karyotype in leukocytes and gonadal cells. PCRs of SRY, ZFY and Yqh were performed on DNA from leukocytes and from left gonadal tissue. SRY-PCR products were purified and sequenced. RESULTS A normal SRY sequence was found in both tissues. CONCLUSIONS Despite the predominance of 45,X cells in gonads, some patients in whom SRY is normal can develop testes, probably due to the presence of alternative mechanisms involved in testicular differentiation; however, further gonadal development could be impaired.

Artículo de revisiónAspectos genéticos y neuroendocrinos en el trastorno del espectro autistaGenetic and neuroendocrine aspects in autism spectrum disorder

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder.

Aspectos genéticos y neuroendocrinos en el trastorno del espectro autista

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder.