Placenta and uterus transcriptomes from transgenic mice expressing human corticotropin-releasing hormone in placenta

Purpose: Parturition is delayed by approximately 12 hours in transgenic mice expressing human corticotropin-releasing hormone (CRH) in placenta. The goal of the study was to identify the pathways in reproductive tissues (uterus and placenta) altered by placental expression of human CRH. Methods: Human BAC RP11-366K18 (CHORI) containing human CRH and cis-regulatory region was inserted into the mouse genome by microinjection and random integration to create the BAC1 line. The CRISPR/Cas9 system was used to delete a CRH regulatory element from the BAC1 line to create the CR1 line, eliminating expression of CRH in placenta. Total expression of uterus and placenta by RNA-seq at embryonic day 18.5 were compared between BAC1, CR1, and nontransgenic mice. Results: Genes known to be associated with luteolysis and initiation of parturition (Cav1, Gja1, Oxtr, Ptgs1, Ptgs2) were not differentially expressed in uterus of this model. Conclusions: CRH-mediated delay of parturition is likely independent of luteolysis. Overall design: mRNA-seq was performed on uterus and placenta harvested at embryonic day 18.5 from nontransgenic mice, Tg(BAC1) mice, and Tg(CR1) mice.

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Dunn-Fletcher CE, Muglia LM, Pavlicev M, Wolf G, Sun MA, Hu YC, Huffman E, Tumukuntala S, Thiele K, Mukherjee A, Zoubovsky S, Zhang X, Swaggart KA, Lamm KYB, Jones H, Macfarlan TS, Muglia LJ