Thirty two adult female albino rats were randomized into 2 main groups (control and experimental). The control group (n=8) received IM injection of 0.3 ml of the drug vehicle (castor oil & benzyl benzoate) once every 5 days for 6 times. 50% of rats of this group were scarificed after 24 hours of the last injection while the other 50% were left for 15 days. Experimental group was divided into 2; experimental group 1; E1 (n=12) received IM injection of 1.5 mg/kg BW of the drug (Mesigyna), once every 5 days for 6 times, and were sacrificed 24 hours after the last injection. Experimental group 2; E2 (n=12) were injected as in group E1 then left for 15 days. Uterine tissue was used for various techniques; histological (H&E & Masson's trichrome) and immunohistochemical (staining of progesterone receptors, using Labeled-Streptavidin method).
Both qualitative and quantitative analyses were done to assess the degree of uterine affection. Quantitative measurements (optical density, color area percentage, line distance & cells count) were performed using the image analyzer. Mesigyna injection showed increased endometrial folding (91.6% of the animals) with decreased endometrial thickness. Luminal epithelium showed proliferation with pseudostratification of its nuclei (75% of animals), necrotic changes (31.3% of animals), hyperplasia (epithelial tufting; in 25% of animals) and desquamation (8.3%of animals). Increased gland size and stromal hypercellularity were also observed. Polymorphonuclear cellular infiltration in both endometrium and myometrium, Vascular congestion and increased myometrial thickness were respectively seen in 83.33%, 63.5 %, 83.5% of E1 group animals. Mesigyna also caused reduction in the amount of collagen fibers. Immunostaining revealed decreased number and optical density of progesterone receptors in nuclei of surface epithelium, glandular epithelium and stromal cells while they were increased in nuclei of smooth muscle fibers. Image analysis results confirmed both the histological and the immunohistochemical results. After withdrawal of the drug (group E2), results showed reduction in necrotic changes, endometrial folding, epithelial tufting and hyperplasia. However there was an aggravation of Polymorphonuclear infiltration, vascular congestion and immunohistochemical changes which indicated delayed recovery of these changes in rat uterus under the effect of Mesigyna.
In conclusion Mesigyna was found to produce severe histopathological changes which were not completely recovered after 15 days of drug stoppage.