Histomorphometric Dynamics of the Uterine Compartments Under Ricinus Communis Linn, Clomiphene Citrate, and Exogenous Estrogen Interventions

Synthetic endocrine modulators like Clomiphene Citrate (CC) and exogenous estrogens are vital clinical tools for managing infertility, but they exhibit structural paradoxes, such as severe endometrial thinning or hyperproliferative risks. Ethnopharmacological alternatives, notably Ricinus communis Linnaeus (RC), are widely used in traditional medicine as fertility regulators or primitive contraceptives; however, their tissue-specific micro-anatomical dynamics remain poorly characterized. This study compared the histomorphological, histomorphometric, and immunohistochemical effects of RC seed extract, CC, and exogenous estrogen (17β estradiol) on the uterine and ovarian compartments of adult cyclic Wistar rats (Rattus norvegicus). Forty (40) cyclic female Wistar rats were divided into seven cohorts (n = 4). Negative Control (Normal Saline); Anti-Estrogen Control (Clomiphene Citrate, 0.00071 mg/kg); Combination Group (CC + RC); Positive Control (Conjugated Estrogen, 8.9 µg/kg); and three Ricinus communis lipid-fraction (RICOM 1013-J) groups administered subcutaneously at 0.6 g/kg, 1.2 g/kg, and 1.8 g/kg body weight. Vaginal cytology was monitored daily. Serum concentrations of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Estradiol (E2) were quantified via Enzyme-Linked Immunosorbent Assay (ELISA). Uterine and ovarian tissues were processed for Hematoxylin and Eosin (H&E) staining and immunohistochemical (IHC) localization of Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Histomorphometric parameters of uterine luminal epithelium, glandular epithelium, and stromal thickness were quantified. Phytochemical screening of the RC extract revealed a high abundance of flavonoids, alkaloids, and phytosterols. Exogenous estrogen induced pronounced endometrial hyperproliferation and significant upregulation of uterine luminal and glandular epithelial thickness, mediated by an increased ERα/ERβ expression. Conversely, CC treatment triggered a clinical paradox: central neuroendocrine activation (elevated serum FSH and LH) accompanied by peripheral anti-estrogenic uterine devastation, resulting in a significantly thinned luminal epithelium and high stromal condensation. Ricinus communis extract demonstrated dual selective estrogen receptor modulator (SERM)-like properties. It maintained a balanced uterine ERαERβ expression, preventing hyperproliferation, but induced marked granulosa cell apoptosis and follicular atresia in the ovary, significantly reducing the functional corpus luteum pool and suppressing the pre-ovulatory LH surge. These findings demonstrate that Ricinus communis seed extract acts as a potent tissue-specific endocrine modulator. While it shields the uterine compartments from the hyperproliferative risks associated with exogenous estrogen, its profound anti-folliculogenic and anovulatory actions in the ovary scientifically validate its traditional use as a primitive contraceptive agent.