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Biol Reprod. 2012 Dec 21;87(6):140. doi: 10.1095/biolreprod.112.104240. Print 2012 Jun.

Truncation of MIMT1 gene in the PEG3 domain leads to major changes in placental gene expression and stillbirth in cattle.

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Livestock Biotechnology, Technische Universität München, Freising, Germany.


We previously identified a microdeletion (Del) in the maternally imprinted PEG3 domain in cattle that results in loss of paternal MIMT1 expression and causes late-term abortion and stillbirth. The mutation, when inherited from the sire, is semilethal for his progeny, with 85% mortality. Here we precisely delineate the deletion and describe comparative analyses of fetuses carrying the deletion with wild-type (WT) siblings. Global DNA methylation analysis of cotyledon tissue revealed greater global CpG methylation in fetuses with the deletion (P = 0.003). Gene expression microarray analyses identified increased NPSR1A, IL1RN, NOS3, IL4R, ZDHHC22, and SMOC2 expression in fetuses carrying the deletion and decreased GRID1, PLG, and IGF1 expression. Involvement of the NPSR1A, IL1RN, NOS3, and IL4R genes suggests that some form of restriction related to blood supply, perhaps hypoxemia, may play a role in the pathological mechanism. Also, imprinted genes known to play a role in mammalian prenatal development, specifically IGF2, DLK1, MEST, AST1, PEG3, APEG3, and H19, showed differential expression. The most striking difference was abundant abnormal expression of the neuropeptide S receptor 1 (NPSR1) gene in placental cotyledon tissue of 7 of 11 MIMT1(Del/WT) fetuses. The similarity of this proportion to that of the semilethal mortality rate suggests that abnormal NPSR1 expression may be linked to death or survival of MIMT1(Del/WT) fetuses. NPSR1 is expressed as two isoforms (A and B), and isoform A was detected in MIMT1(Del/WT) cotyledons. NPSR1A is normally not expressed in placenta. Its role in the stillbirth phenomenon has yet to be elucidated, but it may provide a useful prognostic indicator.

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