Pre-pubertal treatment with a GnRH agonist in bitches-Effect on the uterus and hormone receptor expression

Aim of the study was to examine the effect of deslorelin on uterine tissues of eleven pre-pubertal bitches aged 4.2 ± 0.6 m. Implants containing placebo (sodium chloride 0.9%; n = 4, G I), 4.7 mg (n = 3, GII) or 9.4 mg (n = 4, GIII) deslorelin acetate (Suprelorin^® ; Virbac, France), were administered subcutaneously. Signs of oestrus, vaginal cytology, serum progesterone (P4) and estradiol-17β (E2) concentrations were monitored until the occurrence of oestrus. Bitches were ovariohysterectomized and sections from the uterine tissue were subjected to immunohistochemistry (IHC) for detection of GnRH receptor (R), Kisspeptin (KP)10, Kisspeptin receptor (GPR54), androgen receptor (AR), oestrogen receptor (ER) α,β, and progesterone receptor (PR). Tissue sections were scored semi-quantitatively using an immunoreactivity score (IRS) ranging from 0 to 300 (3). Since some animals were ovariohysterectomized before puberty (n = 1 from GII and n = 2 from GIII), and some in metestrus (all controls and 2 from GII and GIII each), results from these animals were separately evaluated and compared to the controls. Results: No abnormalities were seen in uterine tissues. Kisspeptin 10 expression was low in all cell types, highest IRS were seen in the vascular endothelial cells. The GPR54 was mainly detected in the luminal epithelial cells, superficial and deep uterine glands. The expression of GPR54 and ERα,β was especially high in bitches operated prepubertally. No difference was observed between the controls and experimental bitches operated in their first metestrus. The PR and ERα,β were exclusively expressed in superficial and deep uterine glands and luminal surface epithelial cells. The AR and GnRH-R expression was negative in all cells of all groups. We conclude that application of 4.7 or 9.4 mg deslorelin at the age of 4 months did not cause uterine disturbances. GPR54 expression might be influenced by pre-pubertal deslorelin treatment or the changings related to approaching puberty; the latter is supposed in case of ERα,β.