Foxl2 functions in sex determination and histogenesis throughout mouse ovary development

Background. Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, e.g., Rspo1. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit. Results. Following Foxl2 loss, early testis genes (including Inhbb, Dhh, and Sox9) and several novel ovarian genes were consistently dysregulated during embryonic development. In the absence of Foxl2, expression changes affecting a large fraction of pathways were opposite those observed in Wnt4-null ovaries, reinforcing the notion that these genes have complementary actions in ovary development. Loss of one copy of Foxl2 revealed strong gene dosage sensitivity, with molecular anomalies that were milder but resembled ovaries lacking both Foxl2 alleles. Furthermore, a Foxl2 transgene disrupted embryonic testis differentiation and increased the levels of key female markers. Conclusion. The results, including a comprehensive principal component analysis, 1) support the proposal of dose-dependent Foxl2 function and anti-testis action throughout ovary differentiation; and 2) identify candidate genes for roles in sex determination independent of FOXL2 (e.g., the transcription factors IRX3 and ZBTB7C) and in the generation of the ovarian reserve downstream of FOXL2 (e.g., the cadherin-domain protein CLSTN2 and the sphingomyelin synthase SGMS2). The gene inventory is a first step toward the identification of the full range of pathways with partly autonomous roles in ovary development, and thus provides a framework to analyze the genetic bases of female fertility

Sul test di esclusione del colore. - I Valutazione della concentrazione ottimale [On the dye exclusion of test cell vitality. I. Evaluation of the optimal concentration]

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Sul test di esclusione del colore. - II Influenza di sostanze macromolecolari neutre. [On the dye exclusion test of cell vitality. II. Influence of neutral macromolecular substances.]

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Genetics of the ovarian reserve

Primordial follicles or non-growing follicles (NGFs) are the functional unit of reproduction, each comprising a single germ cell surrounded by supporting somatic cells. NGFs constitute the ovarian reserve, prerequisite for germ cell ovulation and the continuation of the species. The dynamics of the reserve is determined by the number of NGFs formed and their complex subsequent fates. During the reproductive lifespan, the ovarian reserve progressively diminishes due to follicle atresia as well as recruitment, maturation, and ovulation. The depletion of the ovarian reserve is the major determining driver of menopause, which ensues when the number of primordial follicles falls below a threshold of ~1,000. Therefore, genes and processes involved in follicle dynamics are particularly important to understand the process of menopause, both in the typical reproductive lifespan and in conditions like primary ovarian insufficiency (POI), defined as menopause before age 40. Genes and their variants that affect the timing of menopause thereby provide candidates for diagnosis of and intervention in problems of reproductive lifespan. We review the current knowledge of processes and genes involved in the development of the ovarian reserve and in the dynamics of ovarian follicles

Germ cell formation from embryonic stem cells and the use of somatic cell nuclei in oocytes

Embryonic stem cells (ESCs) have remarkable properties of pluripotency and self-renewal, along with the retention of chromosomal integrity. Germ cells function as a kind of "transgenerational stem cells," transmitting genetic information from one generation to the next. The formation of putative primordial germ cells (PGCs) and germ cells from mouse and human ESCs (hESCs) has, in fact, been shown, and the apparent derivation of functional mouse male gametes has also been described. Additionally, investigators have successfully reprogrammed somatic nuclei into a pluripotent state by inserting them into ESCs or oocytes. This would enable the generation of ESCs genetically identical to the somatic cell donor and their use in cell therapy. However, these methodologies are still inefficient and their mechanisms poorly understood. Until full comprehension of these processes is obtained, clinical applications remain remote. Nevertheless, they represent promising tools in the future, enhancing methods of therapeutic cloning and infertility treatment

Incidence of non-age-dependent chromosomal abnormalities: a population-based study on 88965 amniocenteses

Current knowledge about the incidence of chromosomal abnormalities in the general population comes from studies in newborns carried out in the 70s, before the era of widespread prenatal diagnosis. In the following years, data on frequency of chromosomal abnormalities in the second trimester of pregnancy have been used in conjunction with the data on the natural history of chromosomally abnormal fetuses to infer maternal age-specific rates of cytogenetic abnormalities in live-born infants. Starting from the data gathered in 1995–1996 from all Italian cytogenetic laboratories (with 92% compliance to the study), we have compared the frequency of chromosomal abnormalities at amniocentesis in cases with maternal age of ≥35 years (51 758 individuals) and cases with maternal age of <35 years (37 207 cases). The comparison confirmed the age-dependency of aneuploidies, whereas none of the structural abnormalities showed age-related differences. Furthermore, among the mosaic aneuploidies, trisomy 21 and 45,X/46,XX were found with a significantly higher incidence in older women. Chromosomal abnormalities that showed no significant difference between the two groups were summed for the overall national cohort, providing a general estimate of the incidence in the second trimester of pregnancy. The data provide critical background information for prenatal genetic counseling and for the planning of health care policy

Sul test di esclusione del colore. - I Valutazione della concentrazione ottimale [On the dye exclusion of test cell vitality. I. Evaluation of the optimal concentration]

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Il gene SHOX e il suo ruolo nei disturbi dell\u2019accrescimento

no abstrac