Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes.

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian ('placental') mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy.

Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua.

Various human diseases and pregnancy-related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation. Here we report a protocol differentiating human pluripotent stem cells into endometrial stromal fibroblasts (PSC-ESFs) that are highly pure and able to decidualize.

Evolutionary transcriptomics implicates in the origins of implantation and regulation of gestation length.

The developmental origins and evolutionary histories of cell types, tissues, and organs contribute to the ways in which their dysfunction produces disease. In mammals, the nature, development and evolution of maternal-fetal interactions likely influence diseases of pregnancy. Here we show genes that evolved expression at the maternal-fetal interface in Eutherian mammals play essential roles in the evolution of pregnancy and are associated with immunological disorders and preterm birth.

Derivation of endometrial gland organoids from term placenta.

A limitation of current methods for the generation of endometrial gland organoids is their reliance on decidua isolated from endometrial biopsies or elective abortion. Here we report the establishment of endometrial gland organoids from decidua isolated from term placental membranes. These organoids express typical markers of glandular epithelia such as E-cadherin, Laminin and Cytokeratin 7, and can be propagated in cell culture through multiple passages.

Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage.

The steroid hormone progesterone, acting through the progesterone receptor (PR), a ligand-activated DNA-binding transcription factor, plays an essential role in regulating nearly every aspect of female reproductive biology. While many reproductive traits regulated by PR are conserved in mammals, Catarrhine primates evolved several derived traits including spontaneous decidualization, menstruation, and a divergent (and unknown) parturition signal, suggesting that PR may also have evolved divergent functions in Catarrhines. There is conflicting evidence, however, whether the progesterone receptor gene (PGR) was positively selected in the human lineage.

An integrated holo-enhancer unit defines tissue and gene specificity of the Fgf8 regulatory landscape.

Fgf8 encodes a key signaling factor, and its precise regulation is essential for embryo patterning. Here, we identified the regulatory modules that control Fgf8 expression during mammalian embryogenesis. These enhancers are interspersed with unrelated genes along a large region of 220 kb; yet they act on Fgf8 only.

Interactions of quercetin and its lanthane complex with double stranded DNA/RNA and single stranded RNA: spectrophotometric sensing of poly G.

Spectrophotometric titrations revealed that stability of the quercetin/double stranded (ds) DNA or double stranded (ds) RNA non-covalent complexes is significantly higher compared to the quercetin/ss-RNA complexes. This observation can easily be correlated with the significantly larger aromatic surface of base pairs compared to single nucleobases, and it is in good agreement with other experimental data pointing toward intercalative binding mode of quercetin. Fluorescence increase of quercetin induced by ds-RNA is significantly stronger than observed for ds-DNA, offering usage of quercetin as the ds-RNA selective fluorescent probe.

A novel bis-phenanthridine triamine with pH controlled binding to nucleotides and nucleic acids.

The new bis-phenanthridine triamine is characterised by three pK(a) values: 3.65; 6.0 and >7.