Authors : F. Shinku; M. A. Wazhi; V. E. Odey; P. Nyango; M. B. Mohammed; C. N. Edeh; N. Z. Nden; S. S. Gotom; J. S. Kumbet; S. A. Adamu; N. J. Chuwang; Y. M. Usman; M. O. Omolara; R. J. Kutshik; R.T. Mcneil

Volume/Issue : Volume 11 - 2026, Issue 7 - July

Google Scholar : https://tinyurl.com/fhermywd

Scribd : https://tinyurl.com/mw7b3xcn

DOI : https://doi.org/10.38124/ijisrt/26jul999

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Serum hormonal profiling via Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that while CC elevated gonadotropin output via central receptor blockade, high-dose RC and exogenous estrogen generated conflicting biochemical feedback loops that significantly suppressed Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) surges, blocking the pre-ovulatory stimulus. Histological analysis via Hematoxylin and Eosin (H&E) staining showed that exogenous estrogen induced significant Estrogen Receptor Alpha (ERα)-mediated hyperproliferation in the uterine lumen and glandular epithelium, whereas CC caused anti-estrogenic endometrial thinning and glandular atrophy. Conversely, RC extract limited uterine hyperproliferation while maintaining structural boundaries. Ovarian morphometry revealed that RC extract induced marked follicular atresia and a significant reduction in active corpora lutea, establishing a clear anti-fertility footprint. Immunohistochemical (IHC) mapping via semi-quantitative scoring confirmed that RC extract altered the crucial ERα to Estrogen Receptor Beta (ERβ) expression within both endometrial and ovarian granulosa compartments, operating similarly to a Selective Estrogen Receptor Modulator (SERM). These results provide a robust, evidence-based toxicological link validating the traditional empirical use of Ricinus communis as a primitive contraceptive agent.

Keywords : Ricinus communis, Estrogen Receptors (ERα/ERβ), Immunohistochemistry, Uterus, Ovary, Wistar Rats, Selective Estrogen Receptor Modulator (SERM).

References :

1. Ayodeji, O. A., & Roland, N. V. (2020). Neuroendocrine coordination of the hypothalamic-pituitary-gonadal axis in rodent models. Journal of Anatomical Sciences, 11(2), 145–152.
2. Bancroft, J. D., & Gamble, M. (2008). Theory and practice of histological techniques (6th ed.). Edinburgh, Scotland: Churchill Livingstone.
3. Brahmi, F. (2024). Ethnopharmacological systems and botanical family planning alternatives in traditional medicine. Journal of Ethnopharmacology, 312, 116–128.
4. Brahmi, F., Madani, K., & Lanez, T. (2025). Phytochemical indices and female reproductive bioactivities of Ricinus communis Linnaeus: A matrix review. Phytomedicine, 124, 104–118.
5. Couse, J. F., Yates, M. M., Walker, V. R., & Korach, K. S. (2005). Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null Mice: Essential roles for ERalpha and ERbeta in folliculogenesis and ovulation. Molecular Endocrinology, 19(12), 3084–3096.
6. Dupont, S., Krust, A., Gansmuller, A., Dierich, A., Chambon, P., & Mark, M. (2000). Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on the mouse reproductive tract. Development, 127(19), 4277–4291.
7. Farzaneh, S., & Zarghi, A. (2016). Estrogen receptor ligands: A review on recent developments of nuclear estrogen receptor alpha and beta modulators. Scientia Pharmaceutica, 84(3), 409–427.
8. Faustino-Rocha, A. I., da Silva, A., & Oliveira, P. A. (2023). Molecular fragmentation of botanical interaction with systemic nuclear receptor signaling. Experimental and Toxicologic Pathology, 75(2), 112–124.
9. Hamilton, K. J., Hewitt, S. C., Arao, Y., & Korach, K. S. (2017). Estrogen receptors alpha and beta: Structural insights, tissue distribution, and clinical significance. Endocrine Reviews, 38(5), 440–463.
10. Kaipia, A., & Hsueh, A. J. (1997). Regulation of ovarian follicle atresia by apoptosis. Frontiers in Neuroendocrinology, 18(2), 137–158.
11. Kamath, M. S., & George, K. (2011). Letrozole or clomiphene citrate for ovulation induction in unexplained infertility: A central neuroendocrine review. Journal of Human Reproductive Sciences, 4(3), 115–121.
12. Kevin, P. R., Thomas, S., & Amber, L. (2024). Hormonal surges during the pre-ovulatory proestrus phase in Rattus norvegicus. Endocrinology Research, 169(3), 212–224.
13. Kowalczyk, J., Landowski, P., & Smith, R. (2022). Quantitative phytochemical screening and ovarian toxicity profiles of crude Ricinus communis seed extracts. Toxicological Sciences, 186(1), 54–67.
14. Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., ... & Gustafsson, J. Å. (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology, 139(10), 4252–4263.
15. Mbi Feh, M., Patterson, D., & Roberts, J. E. (2024). Comparative tissue hyperproliferation induced by synthetic oestrogens and selective estrogen receptor modulators. Journal of Clinical Endocrinology, 42(4), 310–321.
16. McCarty, K. S., Miller, L. S., Cox, E. B., Konrath, J., & McCarty, K. S. (1985). Estrogen receptor analyses: Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Archives of Pathology & Laboratory Medicine, 109(8), 716–721.
17. McGee, E. A., & Hsueh, A. J. (2000). Initial and cyclic recruitment of ovarian follicles. Endocrine Reviews, 21(2), 200–214.
18. Nakagawa, K., Takahashi, C., & Sugiyama, R. (2014). Clinical paradox of clomiphene citrate: Evaluation of ovulation induction versus endometrial receptivity failure. Reproductive Medicine and Biology, 13(2), 65–72.
19. Nephew, K. P., Long, X., Osbourn, R. E., & Young, P. C. (2000). Macro-level organ analysis versus visual cellular morphometry in tracking endocrine disruptions. Microscopy and Microanalysis, 6(3), 204–215.
20. Patisaul, H. B., & Jefferson, W. (2010). The pros and cons of phytoestrogens. Frontiers in Neuroendocrinology, 31(4), 400–419.
21. Pelletier, G., El-Alfy, M., & Labrie, F. (2000). Cellular localization of estrogen receptors alpha and beta in the female rat reproductive tract as determined by immunohistochemistry. Journal of Histochemistry & Cytochemistry, 48(4), 481–493.
22. Rebar, R. W. (2018). Evaluation of selective estrogen receptor modulators (SERMs) in anovulatory infertility management. Fertility and Sterility, 109(5), 752–760.
23. Salami, S. A., & Raji, Y. (2015). Evaluation of anti-fertility and estrogenic configurations of Ricinus communis seed extracts in cyclic female rats. Nigerian Journal of Physiological Sciences, 30(1), 23–31.
24. Taylor, C. R., & Rudbeck, L. (2013). Immunohistochemical staining methods (6th ed.). California, CA: Dako/Agilent Technologies.
25. Wada, I., Hsu, C. C., & Gadir, A. A. (2004). Endometrial thinning and implantation failure associated with prolonged clomiphene citrate therapy. Human Reproduction, 19(4), 812–819.
26. Xiaodi, W., Zhang, L., & Müller, M. (2024). Characterization of structural and cytological markers across the cyclic phases of the female mammalian estrous cycle. Biology of Reproduction, 110(1), 78–89.
27. Yoest, K. E., Cummings, J. A., & Becker, J. B. (2019). Estrus cycle regulation of neuroendocrine and behavioral receptivity in female rodents. Frontiers in Neuroendocrinology, 53, 100–112.