Preeclampsia (PE) differentially impairs female and male fetal endothelial cell function, which is associated with an increased risk of adult‐onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA‐29a‐3p and 29c‐3p (miR‐29a/c‐3p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex‐dependent manner. RT‐qPCR analysis of miR‐29a/c‐3p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) pregnancies and PE. Bioinformatic analysis of an RNA‐seq dataset was performed to identify PE‐dysregulated miR‐29a/c‐3p target genes in female and male P0‐HUVECs. Gain‐ and loss‐of‐function assays were conducted to determine the effects of miR‐29a/c‐3p on endothelial monolayer integrity and proliferation in response to transforming growth factor‐β1 (TGFβ1) and tumour necrosis factor‐α (TNFα) in NT and PE HUVECs at passage 1. We observed that PE downregulated miR‐29a/c‐3p in male and female P0‐HUVECs. PE dysregulated significantly more miR‐29a/c‐3p target genes in female vs. male P0‐HUVECs. Many of these PE‐differentially dysregulated miR‐29a/c‐3p target genes are associated with critical cardiovascular diseases and endothelial function. We further demonstrated that miR‐29a/c‐3p knockdown specifically recovered the PE‐abolished TGFβ1‐induced strengthening of endothelial monolayer integrity in female HUVECs, while miR‐29a/c‐3p overexpression specifically enhanced the TNFα‐promoted cell proliferation in male PE HUVECs. In conclusion, PE downregulates miR‐29a/c‐3p expression and differentially dysregulates miR‐29a/c‐3p target genes associated with cardiovascular diseases and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex‐specific endothelial dysfunction observed in PE. imageKey points Preeclampsia differentially impairs female and male fetal endothelial cell function in responses to cytokines. Pro‐inflammatory cytokines are elevated in maternal circulation during pregnancy in preeclampsia. MicroRNAs are critical regulators of endothelial cell function during pregnancy. We have previously reported that preeclampsia downregulated microRNA‐29a‐3p and 29c‐3p (miR‐29a/c‐3p) in primary fetal endothelial cells. However, it is unknown if PE differentially dysregulates the expression of miR‐29a/c‐3p in female and male fetal endothelial cells. We show that preeclampsia downregulates miR‐29a/c‐3p in male and female HUVECs and preeclampsia dysregulates cardiovascular disease‐ and endothelial function‐associated miR‐29a/c‐3p target genes in HUVECs in a fetal sex‐specific manner. MiR‐29a/c‐3p differentially mediate cell responses to cytokines in female and male fetal endothelial cells from preeclampsia. We have revealed fetal sex‐specific dysregulation of miR‐29a/c‐3p target genes in fetal endothelial cells from preeclampsia. This differential dysregulation may contribute to fetal sex‐specific endothelial dysfunction in offspring born to preeclamptic mothers.

The paper sets out the importance of dairy sheep in the economies of the Mediterranean Basin and points to the world shortage of ewe's milk, and the increasing demand for it, both as milk and as the products made from it, much of today's demand being met from cow's milk substitutes for original sheep products. The dairy ewe is described. Five thousand ewes, the nucleus of a new industry, are being milked in Britain today in both autumn and spring lambing flocks. Tables show the milk yields from different breeds; the composition of ewe's milk compared to that of the goat and cow; and the contribution of ewe's and cow's milk to the human daily needs of minerals and vitamins. Some of the unique qualities of ewe's milk in the making of products are discussed as well as its behaviour in the making of cheese. Its special properties in the field of food intolerances are touched on. The sheep is suggested as an alternative dairy animal.

Introduction: Preeclampsia (PE) differentially impairs female and male fetal endothelial cell function which is associated with the increased risks of adult-onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA-29a-3p and 29c-3p (miR-29a/c-3p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex-dependent manner. Methods: RT-qPCR analysis of miR-29a/c-3p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) and PE pregnancies. Bioinformatic analysis of an RNAseq dataset was performed to identify PE-dysregulated miR-29a/c-3p target genes in female and male P0-HUVECs. Gain- and loss-of-function assays were conducted to determine the effects of miR-29a/c-3p on endothelial monolayer integrity and proliferation in response to TGFβ1 and TNFα in NT and PE HUVECs at passage 1. Results: PE downregulated miR-29a/c-3p in male, but not female P0-HUVECs. PE dysregulated significantly more miR-29a/c-3p target genes in female vs. male P0-HUVECs. Many of these PE-differentially dysregulated miR-29a/c-3p target genes are associated with critical cardiovascular diseases and endothelial functions. We further demonstrated that miR-29a/c-3p knockdown specifically recovered the PE-abolished TGFβ1-induced strengthening of endothelial monolayer integrity in female HUVECs, while miR-29a/c-3p overexpression specifically enhanced the TNFα-promoted cell proliferation in male PE HUVECs. Conclusions: PE differentially dysregulates miR-29a/c-3p and their target genes associated with cardiovascular diseases- and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex-specific endothelial dysfunction observed in PE.

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