Estrogen suppression induces papillary gingival overgrowth in pregnant baboons

Background: Alterations in sex steroids during pregnancy are associated with the development and exacerbation of reactive lesions involving the gingiva. Currently, few experimental animal models similar to humans are available to examine regulatory pathways involving sex steroids and the periodontium. Methods: In the present study, we used the baboon as a novel experimental model for the study of the regulatory actions of estrogen on the periodontium during pregnancy. Pregnant baboons (N = 5) were administered the potent, highly specific aromatase inhibitor CGS 20267 (2 mg/day subcutaneously) daily on days 60 through 165 of gestation (term = 184). Untreated females (N = 10) and females (5) concomitantly administered aromatase inhibitor and estradiol benzoate (2.0 mg/day each subcutaneously) served as controls. Gingival biopsies were taken between days 145 and 165 of gestation. Results: Administration of CGS 20267 in all females suppressed maternal serum concentrations of estradiol by 95% and induced the development of an exuberant papillomatous enlargement of the gingiva by gestational day I 10, with the most prominent development involving the labial aspects of the anterior sextants. None of the untreated pregnant controls or females concomitantly administered aromatase inhibitor and estradiol benzoate developed gingival overgrowth. Thus, estradiol alone prevented the onset of gingival overgrowth induced by estrogen suppression. In all baboons, discontinuation of the aromatase inhibitor at time of cesarean section resulted in spontaneous regression and resolution of the papillomatous hyperplasia within 4 to 6 weeks. Clinically, the gingival papillary overgrowth was erythematous and edematous, with a propensity toward spontaneous subgingival hemorrhage. Histologically, the biopsy specimens demonstrated hyperplasia of the epithelium typified by mild hyperkeratosis, acanthosis, and elongation and isolated anastamoses of rete ridges. Subjacent to the intact epithelium was a loose connective tissue stroma with isolated areas of inflammatory cell infiltrate. Special stains verified the presence of isolated bacterial biofilms; however, no evidence of fungal filaments was present. Histological features suggestive of viral infection were notably absent in the epithelium. No evidence of viral particles or capsids was identified using transmission electron microscopy. Reverse transcription polymerase chain reaction analysis, using a panel of degenerate primers, was negative for papilloma family viruses. Conclusions: These results are consistent with a significant role for estrogen during primate pregnancy in the regulation of cellular proliferation and differentiation within the gingiva. The baboon represents an important experimental model for studying the regulatory actions of estrogen on the periodontium during pregnancy.