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Publication : Fetal Brain Elicits Sexually Conflicting Transcriptional Response to the Ablation of Uterine Forkhead Box A2 (Foxa2) in Mice.

First Author  Dhakal P Year  2021
Journal  Int J Mol Sci Volume  22
Issue  18 PubMed ID  34575858
Mgi Jnum  J:357291 Mgi Id  MGI:6766155
Doi  10.3390/ijms22189693 Citation  Dhakal P, et al. (2021) Fetal Brain Elicits Sexually Conflicting Transcriptional Response to the Ablation of Uterine Forkhead Box A2 (Foxa2) in Mice. Int J Mol Sci 22(18)
abstractText  In this study, we investigated the effects of ablation of uterine Forkhead Box A2 (Foxa2) on gene expression of fetal brain relative to placenta. Using a conditional knockout mouse model for uterine Foxa2, here we show that the lack of uterine Foxa2 elicits a sexually-conflicting transcriptional response in the fetal brain relative to placenta. The ablation of Foxa2 in the uterus altered expression of genes related to growth, nutrient sensing, aging, longevity and angiogenesis among others. In the wildtype mice, these genes were expressed higher in the fetal brain and placenta of males compared to females. However, in mice lacking uterine Foxa2, the same genes showed the opposite pattern i.e., higher expression in the fetal brain and placenta of females compared to males. Based on the known marker genes of mice placenta and fetal brain cells, we further predicted that the genes exhibiting the sexually conflicting expression were associated with vascular endothelial cells. Overall, our study suggests that uterine Foxa2 plays a role in the regulation of the brain-placental axis by influencing the fetoplacental vascular changes during pregnancy.
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