Maternal serum progesterone levels and placental expression of progesterone receptors in insulin-resistant pregnant rats

Abstract

Background: Maternal diabetes is known to impair placental function; however, its effect on placental expression of progesterone/oestrogen receptors and role of the placenta in foetal programming has not been well documented. The study assessed serum progesterone and oestradiol levels, placental morphology, placental progesterone and oestrogen receptors expression in insulin resistant rats.

Methods: Virgin female rats were randomly divided into 2 groups; control group fed normal rat chow and insulin resistant group fed a diet containing 25% fructose w/w orally for 12 weeks. Rats in both groups were mated with proven male rats and presence of sperm cells in vaginal smear the following morning was taken as day 1 of pregnancy. Maternal blood and amniotic fluid samples were obtained and assessed for glucose, insulin, C-peptide, progesterone and oestradiol levels. Quantitative insulin sensitivity check index (QUICKI) was estimated from fasting blood glucose and insulin values. Placental tissues were isolated, weighed and fixed for morphological studies and the expression of oestrogen and progesterone receptors using immunohistochemical technique.

Results: Maternal blood and amniotic fluid glucose, insulin, C-peptide levels, placental weight and diameter were significantly increased; while QUICKI was significantly lower (P < 0.05) in the insulin resistant rats compared to control rats. Placental junctional zones were enlarged due to an increase in the number of glycogen and trophoblast giant cells in the insulin resistant rats. Progesterone receptor expression was down regulated, with no significant difference in oestrogen receptor expression in the insulin resistant rat placentae.

Conclusion: The results suggest that maternal insulin resistance impairs progesterone production, placental morphology and down regulates placental progesterone receptor expression in this animal model of type 2 diabetes mellitus.

Keywords: Insulin resistance, placenta receptors, progesterone, oestradiol, pregnancy