(191) Exogenous Gonadotropin Injections Elevate Pre-Implantation Serum Estradiol Concentrations and Induce Distinct Implantation-Stage Endometrial Morphology Compared to Simulated Coitus in the Domestic Cat     

Rhasaan T.M. Bovell^1,2, Pierre Comizzoli², Elizabeth L. Buckles¹, Ned J. Place¹

¹Department of Population Medicine & Diagnostic Sciences, Cornell University, Ithaca, NY, USA

²Smithsonian National Zoo & Conservation Biology Institute, Washington, DC, USA


Abstract Text:

Exogenous gonadotropins are commonly used to control ovarian function in endangered felids before assisted reproduction, but downstream effects on the felid endometrium are poorly understood. Our objective was to compare endocrinological and histological metrics in implantation-stage uteri collected from domestic cats after hormonal stimulation or simulated coitus. Females were induced to ovulate by injections of equine chorionic gonadotropin and porcine luteinizing hormone (eCG/pLH, n = 11) or by cervicovaginal swabbing (simulated coitus, n = 7). Blood was sampled on days 7 and 15 after ovulation induction, and serum estradiol (E₂) and progesterone (P₄) concentrations were determined by immunoassay. Circulating E₂ concentrations were greater at day 7 following eCG/pLH injections, with a median serum concentration 18x that of controls. No differences between treatments were detected in serum E₂ concentrations at day 15 or serum P<sub>4 concentrations at days 7 or 15. Cats were spayed on day 15, and tissue segments from the proximal, medial, and distal regions of the left uterine horn were formalin-fixed and stained with hematoxylin and eosin. Slides were digitally scanned at 20x magnification and images were manually annotated to measure endometrial area and thickness, glandular epithelial area and thickness, glandular lumen area, and blood vessel area, and to quantify the numbers of glands, glandular lumina, and blood vessels. Within-treatment variation was assessed with ANOVA or Kruskal-Wallis tests, while between-treatment variation was assessed with t- or Mann-Whitney-Wilcoxon tests. Within both treatment groups, significant regional variation was observed in the areas of glands, glandular lumina, and blood vessels, with distinct patterns of regional variation detected in each treatment group. Therefore, comparisons between treatment groups were performed within each region to account for the within-group regional differences in the endometrium. Compared to simulated coitus controls, gonadotropin-injected cats exhibited glands with larger areas and greater epithelial cell heights in all three regions. In line with these observations, glandular epithelium comprised a greater proportion of these cats’ total endometrial area, though glandular density in these cats was reduced compared to controls. Gonadotropin-injected cats also exhibited larger blood vessel areas in all regions. Other measures differed between treatments, but only in specific regions, including greater expansion of glandular lumina in the proximal region and thicker endometrium with fewer visible glandular lumina in the medial region after eCG/pLH injection. The treatment groups did not differ in any region with regard to total endometrial area, number of glands, number or density of blood vessels, or the proportion of endometrial area occupied by blood vessels. Collectively, our results demonstrate that exogenous gonadotropins induce supraphysiological serum E₂ concentrations one week after administration and increase glandular proliferation and blood vessel area within the implantation-stage feline endometrium. These findings highlight potential mechanisms underlying the relatively low pregnancy success rates in felids after assisted reproduction involving exogenous eCG and pLH.