Estrogen-Responsive Gene Modulation by Mentha pulegium L. Extract in Uterine and Ovarian Tissues of Immature Rat

Mentha pulegium L. is reported to contain phytochemicals known to bind to estrogen receptors and modulate estrogenic effects. A hydroethanolic leaf extract of Mentha pulegium L. (MPE) was prepared, and its effects on uterine and ovarian tissues in immature rats were investigated, focusing on transcriptional endpoint-related estrogenic activity. Female Sprague Dawley rats were treated with varying doses of MPE alone or in combination with estradiol for seven days. Gene expression analysis was performed using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to evaluate the effect of MPE on estrogen-responsive biomarkers: Calbindin-D9k (CaBP-9k), Progesterone receptor (Pgr), Trefoil factor 1 (pS2), Intestinal calcium-binding protein integral (Icabp), Integral membrane-associated protein-1 (Itmap1) and Complement component 3 (CC3) genes. In ovarian tissues, MPE treatment decreased CaBP-9k and Icapb expression, with CC3 showing significant decreases in the 200 mg/kg group. Treatments with MPE and estradiol significantly reduced the expression of all estrogen-responsive genes compared to estradiol treatment. In uterine tissues, 1000 mg/kg MPE increased CaBP-9k and pS2 expression significantly but decreased Icapb, CC3, pS2, and Itmap across all treatment groups significantly. Combined estradiol treatment with MPE (500 and 1000) mg/kg showed significantly low CaBP-9k and CC3 expressions. Increased expression of Icapb, Itmap, and pS2 was observed when combined estradiol treatments with MPE (500 and 1000) mg/kg were compared to estradiol treatment. MPE influenced the expression of specific genes in the uterus and ovaries and thus may exhibit endocrine-modulatory activity by multiple mechanisms of action, highlighting its potential complexity in modulating estrogenic responses.