Dietary supplementation of barley and/or dates attenuate hypercholesterolemic‐induced endometrial dysfunction in Wistar albino rats via alleviation of apoptotic pathways and enhancing oxidative capacity

Abstract

Our study was conducted to characterize the efficacy of barley and/or date palm fruits (10%) in alleviation of hypercholesterolemic endometrial insults in obese rat model. Sixty‐four Wistar albino rats were randomized into eight groups (n = 8); control, hypercholesterolemic‐ and hypercholesterolemic‐treated groups. Animals were subjected to treatment for 4 months. After sacrifice, serum and uterine tissues were collected and processed for biochemical, histological, immunohistochemical, and electron microscopic investigations. In hypercholesterolemic rats, the endometrium displayed hyperplasia with necrotic patches in the surface epithelium and its glandular lining cells. Also, there was a remarkable increase in the endometrial thickness and significant decrease in corresponding glandular numbers. Prompted by these findings, immunohistochemical localization revealed that expression of proliferating cell nuclear antigen was downregulated, while cleaved caspase‐3 was upregulated in the endometrial cells in hypercholesterolemic group. Accordingly, there was remarkable depletion of antioxidant enzymatic activities associated with increased lipid peroxidation and apoptotic markers. Contradictory, supplementation of barley and/or dates to hypercholesterolemic groups showed intriguing amelioration for the histological architecture of the endometrium and balancing its oxidative redox. In conclusion, the administration of barley and/or dates confers enhanced synergistic effects in attenuation of hypercholesterolemic induced‐endometrial dysfunction. This is clear evidence that endometrial amelioration was directly linked to the implication of highly potential antioxidant capacity of barley and/or dates phytochemicals, β‐glucan, polyphenols, and other trace elements, which can be utilized to establish a phyto‐therapeutic strategy for activating endometrial cell regeneration. Practical applications Barley and dates confer both hypoglycemic and hypocholesterolemic potentials. Therefore, their ingredients would be implicated in the amelioration of uterine functions in obese women. These favorable potentials were directly linked to the restraining of endometrial inflammation and retrieving the oxidative capacity. Furthermore, our findings demonstrated that barley and dates substantially diminished the expression of TNF‐α, mitigated DNA damage and prevented leukocytic infiltration in the endometrial tissue; based on their high content of dietary phytochemicals, β‐glucan, polyphenols, and other trace elements.

Female infertility and herbal medicine: An overview of the new findings

“…However, the study of Karimi Jashni et al ( 2016 ) showed that the consumption of P. dactylifera extract due to the presence of estrogen‐like compounds reduced the LH to FSH ratio and the number of cystic follicles, modulated estrogen and androgen synthesis, and increased the number of secondary and antral follicles (Karimi Jashni et al., 2016 ). The estrogenic compounds of this plant extract can be used to treat uterine disorders as they have been shown to reduce endometrial tissue degeneration, necrotic patches, and hyperplasia in endometrial glands (El‐Mansi et al, 2019 ).…”

“…The estrogenic compounds of this plant extract can be used to treat uterine disorders as they have been shown to reduce endometrial tissue degeneration, necrotic patches, and hyperplasia in endometrial glands (El-Mansi et al, 2019). (Kumar et al, 2019).…”

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“…Previous studies have demonstrated that hypercholesterolemic rats showed a significant reduction in the antioxidant activities of CAT, and SOD, in addition to an increased number of atretic follicles and relatively decreased antral follicles (Cordier, et al, 2013) [14]. In the same vein, a study by Lin, et al (2017) [15] reported a decreased number of small follicular populations in the ovaries of hypercholesterolemic dams (El-Mansi, et al, 2019) [16].…”

Abnormal Endometrial Receptivity and Oxidative Stress in Polycystic Ovary Syndrome

“…In C57BL/6 mice fed with a high-fat diet, proliferating cell nuclear antigen (PCNA) expression decreased, and activated B cells (NF-κB) and the nuclear factor κ-light chain enhancer of the peroxisome proliferator-activated receptor gamma (PPAR gamma) signaling pathway increased ( Cheng et al, 2018 ). With the increase in OS, the high-fat diet led to increased endometrial cell apoptosis by increasing the expression of 8-hydroxydeoxyguanosine (8-OHdG) ( Heard et al, 2016 ); compared with the control group, the high-fat diet in the hypercholesterolemia rat model promoted oxidative and inflammatory stress and significantly increased tumor necrosis factor-α (TNF-α) and F4/80 macrophage infiltration ( El-Mansi et al, 2019 ). The aforementioned studies all suggest that the impaired lipid pattern in PCOS patients with MetS can activate ROS through a variety of molecular adjustment mechanisms, resulting in an imbalance in OS in the body, especially in the endometrial region, which in turn affects ER and leads to adverse pregnancy outcomes.…”