No abstract

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon-fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied.Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC 50 = 112.8 μM), as evaluated with Annexin-V-Alexa 508 in combination with BOBO-1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH-DA, increased significantly in fetal ovaries exposed to ¼ LC 50 (28.2 μM, a noncytotoxic and relevant occupational exposure concentration) and LC 50 PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells-oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.

Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

Spermatogenesis is a complex and highly regulated developmental process by which round spermatogonial stem cells undergo mitotic proliferation and meiosis, followed by extraordinary differentiation into highly specialized elongated mature sperm. Extensive differences in terms of sperm production such as testicular structure and organization, hormonal regulation are reported between humans and insects, yet it is not known to what extent components of the process could be conserved and furthermore to what extent the underlying genetic regulators could be shared from insects to mammals. We hence take a genomic approach to identify genes which are expressed in the testes of both fly and mouse through in silico analysis and are phylogenetically conserved across metazoans. Fifty eight testis-enriched, phylogenetically conserved from fly to mouse genes were identified. Among them, 12 genes are novel. Detailed characterization of their murine and human homologs indicate most of them are testis-restricted or enriched and developmentally regulated, thus suggesting that they are important regulators of sperm development in mammals and potential human fertility factors. Our results reveal the existence of spermatogenic homologs with similar testicular expression across a large evolutionary distance, further functional study will be needed to explore the functional conservation among those spermatogenic orthologs.

No abstract