Female fertility and environmental pollution

A realistic picture of our world shows that it is heavily polluted everywhere. Coastal regions and oceans are polluted by farm fertilizer, manure runoff, sewage and industrial discharges, and large isles of waste plastic are floating around, impacting sea life. Terrestrial ecosystems are contaminated by heavy metals and organic chemicals that can be taken up by and accumulate in crop plants, and water tables are heavily contaminated by untreated industrial discharges. As deadly particulates can drift far, poor air quality has become a significant global problem and one that is not exclusive to major industrialized cities. The consequences are a dramatic impairment of our ecosystem and biodiversity and increases in degenerative or man-made diseases. In this respect, it has been demonstrated that environmental pollution impairs fertility in all mammalian species. The worst consequences are observed for females since the number of germ cells present in the ovary is fixed during fetal life, and the cells are not renewable. This means that any pollutant affecting hormonal homeostasis and/or the reproductive apparatus inevitably harms reproductive performance. This decline will have important social and economic consequences that can no longer be overlooked

Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker originate from CD44-negative cells

In human prostate cancer (PCa), the neuroendocrine cells, expressing the prostate cancer stem cell (CSC) marker CD44, may be resistant to androgen ablation and promote tumor recurrence. During the study of heterogeneity of the highly aggressive neuroendocrine PCa cell lines PC3 and DU-145, we isolated and expanded in vitro a minor subpopulation of very small cells lacking CD44 (CD44neg). Unexpectedly, these sorted CD44neg cells rapidly and spontaneously converted to a stable CD44high phenotype specifically expressing the CD44v8-10 isoform which the sorted CD44high subpopulation failed to express. Surprisingly and potentially interesting, in these cells expression of CD44v8-10 was found to be induced in stem cell medium. CD44 variant isoforms are known to be more expressed in CSC and metastatic cells than CD44 standard isoform. In agreement, functional analysis of the two sorted and cultured subpopulations has shown that the CD44v8-10pos PC3 cells, resulting from the conversion of the CD44neg subpopulation, were more invasive in vitro and had a higher clonogenic potential than the sorted CD44high cells, in that they produced mainly holoclones, known to be enriched in stem-like cells. Of interest, the CD44v8-10 is more expressed in human PCa biopsies than in normal gland. The discovery of CD44v8-10pos cells with stem-like and invasive features, derived from a minoritarian CD44neg cell population in PCa, alerts on the high plasticity of stem-like markers and urges for prudency on the approaches to targeting the putative CSC

XIV workshop on the development and function of reproductive organs

The XIV Workshop on the Development and Function of Reproductive Organs was held in Rome, from 14-17 September, 2008, at the Congress Centre of the University of Tor Vergata of Villa Mondragone (Rome, Italy). The Workshop was conceived to be a survey of the events from the formation of the gamete precursors, the primordial germ cells, to the development of the preimplantation embryo through female and male gametogenesis in the mouse experimental model. It was divided into six topics including classic and highly-debated current subjects in the field of the biology of reproduction: mammalian primordial germ cells, the formation of the gonads, stem cells and germ cells, gametogenesis from birth to adult (male), gametogenesis from birth to adult (female), and finally fertilization and preimplantation embryo

Structural changes in rat Pneumocystis carinii surface antigens after terbinafine administration in experimental P. carinii pneumonia

Terbinafine is a synthetic antifungal agent which has recently been found to be highly effective against Pneumocystis carinii. This study evaluated the efficacy of terbinafine on rat P. carinii antigenic profile and the immune response by Western blot analysis, in comparison with atovaquone and co-trimoxazole in rats with pneumocystosis. Terbinafine was shown to target two specific major antigens, particularly those of 116 and 35–40 kDa. Antibodies reactive against these moieties were found in all rats treated with atovaquone and co-trimoxazole, but not in those treated with terbinafine. These surface antigen modifications could be related to disease severity and could provide additional information for monitoring the efficacy of this treatment

Mouse oocytes inhibit plasminogen activator production by ovarian cumulus and granulosa cells

Following the preovulatory surge of gonadotropins, the compact layer of cumulus cells in the antral follicle secretes a hyaluronic acid-enriched extracellular matrix and undergoes a morphological change referred to as cumulus expansion. It has been previously shown that a soluble factor(s) produced by the oocyte is required, in combination with FSH, to promote this process. Since such matrix is sensitive to proteases we have now studied the effect of the oocyte on another gonadotropin-controlled follicle cell function, i.e., the synthesis of plasminogen activator (PA). Our data indicate that isolated cumulus cells secrete uPA in the medium and that FSH or dbcAMP increases this production. The presence of the oocyte or the oocyte-conditioned medium greatly reduces uPA synthesis induced by FSH and dbcAMP in cumulus cells by modulating the abundance of its mRNA. The ability of the mouse oocyte to produce such a factor(s) is dependent upon its stage of development, with fully grown oocytes but not growing oocytes or two-cell embryos being able to inhibit uPA synthesis. A preliminary characterization of this factor suggests that it is a heat-unstable protein with an apparent molecular weight above 100 kDa. Thus, the mouse oocytes appear to promote preovulatory matrix accumulation that occurs just prior ovulation by modulating the gonadotropin action on both the synthesis and the degradation of specific matrix component