Endocrine disruptors and spontaneous premature labor: a case control study

<p>Abstract</p> <p>Background</p> <p>Premature labor is a poorly understood condition. Estrogen is thought to play a key role and therefore the labor process may be affected by endocrine disruptors. We sought to determine whether or not an environmental toxicant, DDE, or dietary derived endocrine disruptors, daidzein and genistein, are associated with spontaneous preterm labor.</p> <p>Methods</p> <p>Cases were defined as primiparous patients having a preterm delivery at or before 35 weeks following the spontaneous onset of labor. Controls were defined as primiparous women who delivered on the same day as the cases but at term gestation.</p> <p>Over approximately 1 year, 26 cases and 52 controls were recruited. Subjects agreed to have blood tests on day one postpartum for DDE and for the phytoestrogens genistein and daidzein.</p> <p>Results</p> <p>The mean concentration of DDE was similar in the case and control groups: 4.29 vs 4.32 ng/g lipid p = .85. In the case group, 13/26 had detectable levels of daidzein (range 0.20 – 1.56 ng/ml) compared to 25/52 controls (range 0.21 – 3.26 ng/ml). The mean concentration of daidzein was similar in cases compared to controls: 0.30 vs .34 ng/ml p = 0.91. Of the case group,14/26 had detectable levels of genistein (range 0.20 – 2.19 ng/ml) compared to 32/52 controls (range 0.21 – 2.55 ng/ml). The mean concentration of genistein was similar in cases compared to controls: 0.39 vs 0.31 ng/ml, p = 0.61.</p> <p>Conclusion</p> <p>The serum levels of DDE in this population were found to be low.</p> <p>There appears to be no relationship between serum concentrations of DDE, daidzein, and genistein and spontaneous preterm labor in our population. The inability to identify an effect may be related to the comparatively low concentrations of DDE in our population and the rapid and variable reduction of phytoestrogens from women in labor.</p

Micro-connectomics: probing the organization of neuronal networks at the cellular scale.

Defining the organizational principles of neuronal networks at the cellular scale, or micro-connectomics, is a key challenge of modern neuroscience. In this Review, we focus on graph theoretical parameters of micro-connectome topology, often informed by economical principles that conceptually originated with Ramón y Cajal's conservation laws. First, we summarize results from studies in intact small organisms and in samples from larger nervous systems. We then evaluate the evidence for an economical trade-off between biological cost and functional value in the organization of neuronal networks. Various results suggest that many aspects of neuronal network organization are indeed the outcome of competition between these two fundamental selection pressures.This work was supported by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Nature Publishing Group

Interspecies somatic cell nuclear transfer is dependent on compatible mitochondrial DNA and reprogramming factors

Interspecies somatic cell nuclear transfer (iSCNT) involves the transfer of a nucleus or cell from one species into the cytoplasm of an enucleated oocyte from another. Once activated, reconstructed oocytes can be cultured in vitro to blastocyst, the final stage of preimplantation development. However, they often arrest during the early stages of preimplantation development; fail to reprogramme the somatic nucleus; and eliminate the accompanying donor cell’s mitochondrial DNA (mtDNA) in favour of the recipient oocyte’s genetically more divergent population. This last point has consequences for the production of ATP by the electron transfer chain, which is encoded by nuclear and mtDNA. Using a murine-porcine interspecies model, we investigated the importance of nuclear-cytoplasmic compatibility on successful development. Initially, we transferred murine fetal fibroblasts into enucleated porcine oocytes, which resulted in extremely low blastocyst rates (0.48%); and failure to replicate nuclear DNA and express Oct-4, the key marker of reprogramming. Using allele specific-PCR, we detected peak levels of murine mtDNA at 0.1460.055% of total mtDNA at the 2-cell embryo stage and then at ever-decreasing levels to the blastocyst stage (,0.001%). Furthermore, these embryos had an overall mtDNA profile similar to porcine embryos. We then depleted porcine oocytes of their mtDNA using 10 mM 29,39- dideoxycytidine and transferred murine somatic cells along with murine embryonic stem cell extract, which expressed key pluripotent genes associated with reprogramming and contained mitochondria, into these oocytes. Blastocyst rates increased significantly (3.38%) compared to embryos generated from non-supplemented oocytes (P,0.01). They also had significantly more murine mtDNA at the 2-cell stage than the non-supplemented embryos, which was maintained throughout early preimplantation development. At later stages, these embryos possessed 49.9962.97% murine mtDNA. They also exhibited an mtDNA profile similar to murine preimplantation embryos. Overall, these data demonstrate that the addition of species compatible mtDNA and reprogramming factors improves developmental outcomes for iSCNT embryos