The presence of two active X chromosomes (XaXa) is a hallmark of the ground state of pluripotency specific to murine embryonic stem cells (ESCs). Human ESCs (hESCs) invariably exhibit signs of X chromosome inactivation (XCI) and are considered developmentally more advanced than their murine counterparts. We describe the establishment of XaXa hESCs derived under physiological oxygen concentrations. Using these cell lines, we demonstrate that (1) differentiation of hESCs induces random XCI in a manner similar to murine ESCs, (2) chronic exposure to atmospheric oxygen is sufficient to induce irreversible XCI with minor changes of the transcriptome, (3) the Xa exhibits heavy methylation of the XIST promoter region, and (4) XCI is associated with demethylation and transcriptional activation of XIST along with H3K27-me3 deposition across the Xi. These findings indicate that the human blastocyst contains pre-X-inactivation cells and that this state is preserved in vitro through culture under physiological oxygen.

Multi-foetal gestations remain the principal cause of adverse perinatal outcomes after ART. Singleton ART pregnancies have an increased risk of preterm delivery and low birth weight at term. Non-lethal congenital malformation rates are not increased following ART. Placenta praevia is increased following ART.

In conclusion, a sevenfold increase in laboratory-confirmed CL was observed in southern Israel in 2007-2013, probably reflecting a bigger outbreak, possibly related to urban expansion bordering with CL foci.

No abstract