Abstract / Summary
Abstract Background Monosodium glutamate (MSG) has been linked to uterine alterations in rodents, but how the uterine phenotype is modified by the surrounding steroid milieu remains incompletely understood. This study evaluated whether estradiol and progesterone differentially modify MSG-associated uterine remodeling using integrated endocrine, oxidative, inflammatory and histomorphological endpoints. Methods Thirty-six adult female Wistar rats were allocated to six groups (n = 6): control, MSG only (1000 mg/kg/day, p.o.), estrogen (administered as estradiol valerate) only at 1.5 mg/kg/day, p.o., progesterone only (5 mg/kg/day, i.m.), MSG + estrogen, and MSG + progesterone for 56 days. The experimental unit was the individual rat. The study was conducted under the approved institutional animal-use protocol and reported with reference to ARRIVE 2.0. Serum E2, P4, LH and FSH, and uterine SOD, GSH, MDA, TNF-α and IL-6 were measured. Uterine weight was recorded, and H&E and Masson’s trichrome staining were performed. Data were analyzed using one-way ANOVA with appropriate post-hoc comparisons; P < 0.05 was considered significant. Results Estrogen-only animals had the highest serum E2 (66.13 ± 11.03 pg/mL) and the greatest absolute (0.4450 ± 0.0392 g) and relative (0.2800 ± 0.0489%) uterine weights. MSG + estrogen showed the strongest oxidative-inflammatory response: SOD decreased from 23.44 ± 0.54 to 8.17 ± 0.27 µmol/g tissue and GSH from 0.894 ± 0.037 to 0.408 ± 0.017 µmol/g tissue, whereas MDA increased from 14.09 ± 0.40 to 36.69 ± 1.75 nmol/g tissue (P < 0.0001). TNF-α increased from 67.10 ± 6.04 to 562.30 ± 13.98 pg/mL and IL-6 from 41.84 ± 3.61 to 635.66 ± 24.96 pg/mL in the same group. H&E demonstrated treatment-dependent epithelial, glandular and stromal remodeling. Masson’s trichrome showed conspicuous collagen-rich staining in the estrogen-only and combination groups, although collagen deposition was assessed qualitatively. Conclusion MSG exposure produced hormone-context-dependent uterine remodeling. MSG + estrogen showed the strongest integrated oxidative, inflammatory and histomorphological phenotype, whereas MSG + progesterone displayed a distinct low-mass, collagen-rich remodeling pattern. The findings support further investigation of hormone-modulated MSG-associated uterine remodeling as a fibroid-relevant experimental phenotype, but do not by themselves establish discrete uterine leiomyomas.