Exploring the influence of offspring Peg3 expression on maternal-infant communication and maternal mood in mice and humans

Tyson, Hannah 2021. Exploring the influence of offspring Peg3 expression on maternal-infant communication and maternal mood in mice and humans. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Maternal mental health conditions have been shown to be among the most disruptive influences on the mother-infant bond and their reciprocal social relationship, often resulting in long-lasting, often adverse infant outcomes. However, the mechanisms underlying this are poorly understood. Reduced placental expression of the imprinted gene PEG3 has been linked to prenatal depression in human pregnancy. In mice, intrinsic loss of function of Peg3 in dams has previously been linked to poor maternal care. Reduced expression of Peg3 in the murine feto-placental unit has also been shown to indirectly impair maternal care and increase anxious-like behaviour in wild-type dams. It has been hypothesised that this indirect effect on maternal behaviour may result from defects in the development of the placental endocrine lineages. Together, these studies suggested that reduced placental PEG3 expression may play a causal role in driving maternal mood symptomology and adverse infant outcomes in human pregnancy. Using a Peg3 loss-of-function mouse model, this thesis replicated previous work linking reduced offspring Peg3 expression to impaired maternal care and increased anxiety-like behaviours in wild-type dams with 100% mutant litters. For the first time, this thesis extended previous work, characterising the behaviour of wild-type dams with litters composed of both mutant and wild type pups. Behavioural characterisation of Peg3 mutant offspring revealed a sexually dimorphic effect of Peg3 disruption, highlighting a male-specific deficit in neonatal social behaviour in mutant mice. Later life social impairments were also observed in both mutant and wild-type littermates. Inclusion of wildtype controls allowed for these behavioural changes to be attributed to the adverse maternal environment, likely induced by placental endocrine sufficiency, as opposed to intrinsic loss of function of the Peg3 gene. PEG3 expression and social communication were also explored in mother-infant dyads from the Grown in Wales human cohort. There were no associations with PEG3 and mother-infant social behaviour. However, sexually dimorphic outcomes in response to prenatal depression were observed. Specifically, prenatal maternal mood symptomology was associated with negative aspects of vocalisation in mothers with female, but not male infants. In summary, this thesis provides support for the relationship between placental endocrine dysfunction, maternal behaviour, and offspring outcomes in a Peg3 loss of function model. It also contributes to a growing body of literature suggesting that males are differently affected by disruption of Peg3 expression. Finally, though no association with PEG3 was reported in the human cohort, this thesis highlights the need to study sexually dimorphic outcomes in relation to perinatal maternal mood symptomology, as a mother’s behaviour may be influenced by the sex of their infant.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	25 July 2022
Date of Acceptance:	25 July 2022
Last Modified:	05 Jan 2024 08:08
URI:	https://orca.cardiff.ac.uk/id/eprint/151430

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