Clomiphene citrate modulates the expression of endometrial carbohydrates (especially N-acetyl-d-glucosamine and sialic acid) in pseudopregnant rats

This study investigated the presence of carbohydrates N-acetyl-d-glucosamine and sialic acid oligosaccharides, in the uterine epithelium of pseudopregnant rats treated with ovarian hormones and Clomiphene citrate (CC) a commonly used fertility drug associated with low pregnancy rates. Ovariectomized sexually mature rats were given 0.25 mg CC prior to the implantation-priming hormone sequence of 5 mg progesterone for 3 days and a single dose of 0.5 μg estradiol-17β (E2) on day 3 (PP(PE)) and sacrificed 24 h after the last hormone treatment. Uterine tissue was incubated with the lectin Triticum vulgare (wheat germ agglutinin, WGA), associated with avidin and subsequently labelled with biotinylated-ferritin for electron microscopy, a combined alcian blue/PAS technique for light microscopy and RT-PCR was run for progesterone-associated endometrial protein (PAEP) gene, a pregnancy related endometrial gene that is associated with the protein thought to express carbohydrates in the uterus and suppress immune function. The results indicate that CC administration decreases the expression of these carbohydrates both at a cellular level and genetic level when compared to the PP(PE) group. However, the lowest expression of N-acetyl-d-glucosamine and sialic acid was seen in the placebo group. The ovarian hormones were therefore shown to be important for the synthesis of these carbohydrates that are important in the implantation period and the maintenance of pregnancy. The results suggest that the effect of CC on the expression of N-acetyl-d-glucosamine and sialic acid is a significant reason why there are low pregnancy rates with CC use.