Abstract
Postpartum mood disorders are prevalent in the population, with 14% of new mothers in New Zealand experiencing postpartum depression (PPD). The onset of PPD and other postpartum mood disorders are not well understood, however, recently FDA-approved drugs have been successful in treating PPD. Maternal responsiveness is disrupted in mothers diagnosed with PPD, therefore understanding the onset of maternal behaviour may provide a mechanism for PPD onset. Maternal behaviour is an umbrella term for adaptive behaviours that promote offspring survival through offspring-directed and related behaviours. Pregnancy represents a period of drastic hormonal changes from the non-pregnant state. Key hormones during pregnancy include progesterone, prolactin, estradiol, and oxytocin, which elevate during pregnancy and have been shown to act in the brain to promote the display of maternal behaviour in the postpartum period. The medial preoptic area of the hypothalamus (MPOA) is a nexus for modulating maternal behaviour onset. Prolactin and estrogen-sensitive neurons with the MPOA are critical for maternal behaviour onset in rodents, although how progesterone acts in the MPOA is unclear. This thesis aimed to identify the necessity of progesterone signalling in the MPOA for the onset of maternal behaviour.
To uncover the potential roles of progesterone on maternal behaviour, three Objectives were employed: 1) To identify alterations in progesterone receptor (Pgr), prolactin receptor (Prlr) and estrogen receptor alpha (Esr1) mRNA in the MPOA of wild-type female mice during pregnancy and lactation. This study reports extensive Pgr, Prlr, and Esr1 mRNA overlap in MPOA neurons, which decreases during pregnancy. Interestingly, Prlr + Esr1 mRNA is rarely co-expressed without Pgr mRNA, providing evidence for a potential role for Pgr in regulating estradiol and prolactin/placental lactogen action in the MPOA. 2) To examine the effects of chronic progesterone administration on the display of maternal behaviour in virgin female mice. Subcutaneous implantation of progesterone was utilised to achieve pregnancy-like levels of progesterone in virgin female mice, followed by standard maternal behaviour assays. Progesterone treatment had little effect on pup-directed maternal behaviour, however, progesterone-treated mice built better nests than controls. 3) To determine whether Pgr expression is required for normal maternal behaviour in late-pregnant and lactating mice. Specific deletion of Pgr was completed by viral administration of Cre recombinase into the MPOA of female Pgrlox/lox mice. Mice with reduced Pgr in the MPOA had significantly disrupted maternal behaviour during late pregnancy and lactation, shown by impaired retrieval behaviour in the home cage pup retrieval. These data demonstrate a clear role for progesterone action in the MPOA in promoting offspring-directed behaviours. However, further research is required to understand how MPOA Pgr+ cells influence maternal behaviour circuitry.