Loss of offspring Peg3 reduces neonatal ultrasonic vocalizations and increases maternal anxiety in wild-type mothers

McNamara, G. I., Creeth, H. D. J., Harrison, D. J., Tansey, K. E., Andrews, R. M., Isles, A. R. ORCID: https://orcid.org/0000-0002-7587-5712 and John, R. M. ORCID: https://orcid.org/0000-0002-3827-7617 2018. Loss of offspring Peg3 reduces neonatal ultrasonic vocalizations and increases maternal anxiety in wild-type mothers. Human Molecular Genetics 27 (3) , pp. 440-450. 10.1093/hmg/ddx412

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Abstract

Depression and anxiety are the most common mental health conditions during pregnancy and can impair the normal development of mother-infant interactions. These adversities are associated with low birth weight and increased risk of behavioural disorders in children. We recently reported reduced expression of the imprinted gene PATERNALLY EXPRESSED GENE 3 (PEG3) in placenta of human infants born to depressed mothers. Expression of Peg3 in brain has previously been linked maternal behaviour in rodents, at least in some studies, with mutant dams neglecting their pups. However, in our human study decreased expression was in the placenta derived from the fetus. Here, we examined maternal behaviour in response to reduced expression of Peg3 in the feto-placental unit. Prenatally we found novelty reactivity was altered in wildtype females carrying litters with a null mutation in Peg3. This behavioural alteration was short-lived and there were no significant differences the transcriptomes of either the maternal hypothalamus or hippocampus at E16.5. In contrast, while maternal gross maternal care was intact postnatally, the exposed dams were significantly slower to retrieve their pups and displayed a marked increase in anxiety. We also observed a significant reduction in the isolation-induced ultrasonic vocalisations (USVs) emitted by mutant pups separated from their mothers. USVs are a form of communication known to elicit maternal care suggesting Peg3 mutant pups drive the deficit in maternal behaviour. These data support the hypothesis that reduced placental PEG3 in human pregnancies occurs as a consequence of prenatal depression but leaves scope for feto-placental Peg3 dosage, during gestation, influencing aspects of maternal behaviour.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Biosciences Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Oxford University Press
ISSN:	0964-6906
Funders:	Medical Research Council
Date of First Compliant Deposit:	27 November 2017
Date of Acceptance:	21 November 2017
Last Modified:	03 Jul 2024 01:07
URI:	https://orca.cardiff.ac.uk/id/eprint/107096

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