The effect of fetal sex and antenatal glucocorticoid exposure on placental development in the spiny mouse (Acomys cahirinus)

The primary role of the placenta is the provision of nutrients to the fetus to allow normal fetal growth. Therefore the mechanisms contributing to the differential in utero growth trajectories adopted by the male and female fetus potentially lies within the placenta. Furthermore, complications of pregnancy that appear to affect the male fetus more often, including stress and excess glucocorticoids of maternal origin, may also arise from responses that are primarily of placental origin. However the potential role of the placenta in mediating these effects has not been studied. Using the spiny mouse, we investigated whether placental development across gestation differs depending on the sex of the fetus. Further, we investigated the short- and long-term effects of a brief glucocorticoid pulse, using dexamethasone (DEX), on placental development, with a particular focus on identifying if the DEX-induced placental effects differ for a male or female fetus. Overall the studies contained within this thesis sought to test the hypothesis that the placental response to excess maternal glucocorticoids is sex dimorphic in nature, and this arises from a fundamental difference in placental development that is present between the sexes. Pregnant spiny mouse dams were either killed at gestational ages from day 15 to term (39 days) and placental tissues were weighed and collected; or they underwent DEX or saline administration for 60 h beginning at 0.5 gestation. Dams which underwent treatment were allocated to one of two groups where fetal and placental tissues were collected immediately (day 23), or pregnancy was allowed to continue until day 37 when fetal and placental tissues were then collected (day 37). Placental tissue was processed for histology, or divided into spongy and labyrinth zones and processed for qPCR analysis of selected genes. We showed that the overall size (and weight) of the placenta was similar between the sexes, but the development of the placental regions differed. Further, the spatio-temporal expression pattern of a suite of genes within the labyrinth of placentas of male and female fetuses showed sex dimorphic expression. These observations indicate that the placentas of both males and female fetuses are able to function efficiently across gestation in ‘normal’ pregnancies and achieve optimum fetal growth, albeit by different placental strategies. Immediately following the cessation of DEX administration (day 23), many of the DEX induced effects were observed in placentas of both sexes; however, at day 37 the DEX effects were highly dependent on the sex of the fetus. We suggest that the presence of male-female differences two-weeks after dexamethasone administration indicates that the placenta responds to adverse events in utero in a sex dimorphic manner. These findings show that the development of the placenta for male and female fetuses differs. Further, there is a significant placental response to maternal dexamethasone exposure, the exact nature of which also depends on fetal sex. The extent that these two phenomena are related, and whether they contribute to the greater vulnerability of males to pregnancy complications and stress in utero remains to be fully elucidated.