Effects of naringenin on superovulation in mice: evaluation of zygote and blastocyst development, histopathology, and molecular docking insights

Abstract

CONTEXT: Naringenin is a citrus-derived flavanone with documented antioxidant, anti-inflammatory, and steroidogenic modulatory properties; yet, its effects under gonadotropin-stimulated superovulation have not been investigated. AIMS: This study evaluated the impact of naringenin co-administration during a pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG) superovulation protocol on zygote yield, preimplantation embryo development, and ovarian and endometrial morphology in CD-1 mice. METHODS: Twenty-four females (8-10 weeks) received PMSG with either naringenin (20 mg/kg intraperitoneally; n = 12) or dimethyl sulfoxide vehicle (n = 12), followed by hCG 48 h later and mating with fertile males. Pronuclear-stage embryos were collected from oviducts 14-16 h post-mating and cultured in vitro for 96 h; cleavage and blastocyst formation were assessed at 24 h and 96 h respectively. Ovarian and uterine tissues were evaluated histopathologically. KEY RESULTS: Naringenin treatment significantly increased total zygote yield. Although cleavage rate was lower in the naringenin group (45% vs 53%), blastocyst formation among cleaved embryos was markedly higher (47% vs 25%). Treated animals exhibited significantly greater corpora lutea count, corpora lutea:cell ratio, ovarian diameter, and endometrial thickness. In silico molecular docking predicted favourable binding affinities of naringenin towards the progesterone receptor and follicle-stimulating hormone receptor, generating a computational hypothesis consistent with these in vivo findings. CONCLUSIONS: Naringenin enhances blastocyst developmental competence and post-ovulatory ovarian parameters under superovulation conditions. IMPLICATIONS: These findings support the potential of naringenin as an adjunct to gonadotropin-based reproductive biotechnology protocols.