Allopregnanolone in the brain: protecting pregnancy and birth outcomes

Paula Brunton, John Russell, Jonathan J. Hirst

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

A successful pregnancy requires multiple adaptations in the mother's brain that serve to optimise fetal growth and development, protect the fetus from adverse prenatal programming and prevent premature delivery of the young. Pregnancy hormones induce, organise and maintain many of these adaptations. Steroid hormones play a critical role and of particular importance is the progesterone metabolite and neurosteroid, allopregnanolone. Allopregnanolone is produced in increasing amounts during pregnancy both in the periphery and in the maternal and fetal brain. This review critically examines a role for allopregnanolone in both the maternal and fetal brain during pregnancy and development in protecting pregnancy and birth outcomes, with particular emphasis on its role in relation to stress exposure at this time. Late pregnancy is associated with suppressed stress responses. Thus, we begin by considering what is known about the central mechanisms in the maternal brain, induced by allopregnanolone, that protect the fetus(es) from exposure to harmful levels of maternal glucocorticoids as a result of stress during pregnancy. Next we discuss the central mechanisms that prevent premature secretion of oxytocin and consider a role for allopregnanolone in minimising the risk of preterm birth. Allopregnanolone also plays a key role in the fetal brain, where it promotes development and is neuroprotective. Hence we review the evidence about disruption to neurosteroid production in pregnancy, through prenatal stress or other insults, and the immediate and long-term adverse consequences for the offspring. Finally we address whether progesterone or allopregnanolone treatment can rescue some of these deficits in the offspring.
Original languageEnglish
Pages (from-to)106-136
JournalProgress in neurobiology
Early online date4 Sept 2013
Publication statusPublished - Feb 2014


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