Dexamethasone effect on the extent of IUGR development depends greatly on the dose and the route of administration . The regiment of DEX treatment in the present study was based on literature review in inducing moderate IUGR [16, 29]. Dexamethasone in the present model induced a clear IUGR with 18% reduction in fetal body weight and 30% reduction in placental weight. Dexamethasone also induced a reduction in the detected level of maternal P4 as reported previously [1, 22].
The reduction in maternal serum P4 levels are normal towards the end of pregnancy due to apoptosis of the basal zone . However, DEX treatment exaggerates the apoptotic process in this zone . The basal zone is responsible for hormonal production and increased apoptosis in this zone is believed to lower the levels of placental lactogens secretion that stimulate ovarian P4 production . Hence, leading to lower levels of maternal P4 with DEX treatment as detected in our study.
The regiment of P4 treatment in the present study was modified from previous studies on the effect of P4 on pregnancy outcomes [30, 38]. Progesterone administered did not cause a significant increase in maternal P4 levels compared to C group possibly due to increased excretion of P4 metabolite that was seen when P4 levels increases . However, at 19 dg, maternal P4 levels increased significantly when P4 was co-treated with DEX, possibly due to the lack of DEX inhibitory effect on placental endocrine function after a short DEX exposure (15–18 dg). Another possibility is the effect of DEX on reducing the activity of P4 catabolic enzymes at this gestational age .
The reduction in fetal and placental weights with DEX treatment were associated with lower levels of P4 detected in maternal serum. P4 co-treatment with DEX prevented the reduction in fetal weight. This could be explained by maintaining the weight of placenta and preserving placental function seen with P4 treatment. Placental efficiency, which indicates the placental capability in providing the fetus, was improved with DEX treatment. This may imply that, as a compensatory mechanism, the placenta is preserving fetal weight at the expense of its own growth. The efficiency improved further when DEX was cotreated with P4.
Metastasis tumor antigens are well known for their involvement in the pathway of cell proliferation and apoptosis. MTA1, 2 and 3 have been detected in human  and rat placentas [16, 33]. In the present study, MTA2 was not evaluated because it lacked to prove its significance in placental development and IUGR in DEX-induced IUGR model . MTA1 is known for its role in proliferation and DNA damage repair through upregulating beta-catenin and cyclin D1 [25–27]. Placental growth ceases by 19 dg, indicated by no change in placental weight between 19 and 21 dg seen in the present study and previous studies [16, 31]. Furthermore, placental apoptosis is known to take place towards the end of pregnancy [17, 41]. This is associated to lower level of MTA1 expression detected in the present study in both placental zones by 21 dg compared to 19 dg. The effect of DEX on decreased MTA1 expression was seen in placental basal zone at 19 dg only. Since placental levels of beta-catenin was found to be reduced in DEX-induced IUGR model , it is believed that DEX inhibits the effect of MTA1 by decreasing the expression of beta-catenin and Wnt pathway leading to decreased proliferation seen in IUGR placentas. The basal zone is the zone responsible for hormonal production, any reduction in the size of this zone, as seen with DEX treatment in the present study, would directly affect hormonal production noticed as reduction in P4 level and fetal development.
On the other hand, MTA3 is known for its apoptotic effect by inhibiting beta-catenin and blunting Wnt pathway [27, 28]. Gene and protein expressions of MTA3 did not follow the same patterns in the placental labyrinth zone, possibly due to post-translational modifications. The DEX-treated group at 19 dg showed significant increase in MTA3 protein expression in the LZ. This increase in MTA3 expression and the reduction in the downstream beta-catenin seen in a previous study in the same zone  is believed to be one of the reasons behind decreasing cell proliferation and increasing apoptosis of placental LZ seen with DEX treatment. The LZ is the part of the placenta responsible for nutrient delivery to the fetus. Reduction in fetal body weight seen with DEX treatment could be a direct effect of a reduction in the exchange interface between the mother and the fetus.