Successful pregnancy requires adjustments to multiple maternal homeostatic mechanisms, governed by the maternal brain to support and enable survival of the growing conceptus and placenta. Such adjustments fit the concept of allostasis and have a cost, allostatic load (e.g. gestational diabetes mellitus). Allostasis is driven by ovarian, anterior pituitary, placental and feto-placental hormones acting on the maternal brain: e.g. relaxin stimulates vasopressin secretion, permitting blood volume expansion; prolactin (and placental lactogen) induces leptin resistance, increasing appetite and positive energy balance; allopregnanolone (5α-reduced neuroactive metabolite of progesterone), reduces hypothalamo-hypophysial-adrenal (HPA) axis responses to stressors, conserving energy and limiting fetal programming. Allopregnanolone, produced and acting in the nucleus tractus solitarii (NTS), where 5α-reductase gene (srd5a1) expression is increased in pregnancy, induces opioid inhibition of the stress axis, with up- or down-regulation of key neuropeptide and receptor genes. The expression of hundreds more genes is altered in the maternal brain, starting in pregnancy. An emerging issue is whether allostatic changes in gene expression in the brain involve epigenetic mechanisms (e.g. DNA methylation/ demethylation, histone modifications, or micro (mi)RNAs - which can regulate central srd5a1 expression). There is sparse information about epigenetic changes in the maternal brain in pregnancy, in striking contrast with abundant data about epigenetic changes from early-life experience in offspring brains. Many women carry an existing allostatic load into pregnancy, from socio-economic circumstances, and in ‘developed’ countries, also from obesity. These pregnancies have poorer outcomes, suggesting negative interactions between pre-pregnancy and pregnancy allostatic loads: a bad start. The use of animal models, e.g. adult prenatally stressed female offspring with abnormal metabolic and stress response phenotypes, to probe gene expression changes, and epigenetic mechanisms in the maternal brain in adverse pregnancies will be discussed, with the prospect of translating the information to ameliorate poor pregnancy outcomes.
|Publication status||Unpublished - 13 Jul 2018|
|Event||Parental Brain 2018: Biological and Behavioural Perspectives in Parental Health - Westin Harbour Castle Hotel, Toronto, Canada|
Duration: 13 Jul 2018 → 14 Jul 2018
|Conference||Parental Brain 2018|
|Period||13/07/18 → 14/07/18|