Improvement in the epigenetic modification and development competence in PCOS mice oocytes by hydro-alcoholic extract of Nigella sativa during in-vitro maturation: An experimental study

Abstract

Background: Nigella Sativa (NS) and its active component, thymoquinone, have beneficial protective effects on experimental animal models of polycystic ovary syndrome (PCOS) and different human diseases.
 Objective: The present study aimed to investigate the effects of NS hydro-alcoholic extract (NSE) on the oocyte quality of PCOS mice during in vitro maturation.
 Materials and Methods: For induction of PCOS, 40 prepubertal 21-days old female B6D2F1 mice (18-22 g body weight) received subcutaneous dehydroepiandrosterone daily. After validation of the model, germinal vesicle-stage oocytes of superovulated mice were collected and placed in the culture medium containing different concentrations (0, 1, 50, and 100 μg/ml) of NSE. For the measurement of developmental competency, some mature oocytes were fertilized with epididymal spermatozoa. Other mature oocytes were assessed for oxidative stress. Also, some mRNA expression levels involved in oocyte maturation and epigenetic modification were evaluated.
 Results: The 50 μg/ml NSE treated group showed significantly higher r ates o f maturation, f ertilization, and blastocyst formation in comparison with both control and PCOS groups. A high level of glutathione concentration and glutathione peroxidase mRNA expression, besides a low level of reactive oxygen species content all, were observed in oocytes treated with 50 μg/ml NSE, indicating the modification of oxidative statue. Furthermore, the oocytes in the 50 μg/ml-treated group showed an upregulation of mRNA expression in epigenetic-related genes (Dnmt1 and Hdac1) and maternally derived genes (Mapk and Cdk1), correspondingly downregulation of cyclooxygenase2 mRNA expression, in comparison to other groups.
 Conclusion: The results of this study indicated that 50 μg/ml NSE improves oocyte maturation, oxidative statues and epigenetic modifications. These may be the all reasons for the developmental competency in the control and PCOS mice oocytes. Key words: Epigenetic modification, In-vitro maturation, Nigella sativa, Oxidative stress, Polycystic ovary syndrome. Key words: Epigenetic modification, In-vitro maturation, Nigella sativa, Oxidative stress, Polycystic ovary syndrome.
 Key words: Epigenetic modification, In-vitro maturation, Nigella sativa, Oxidative stress, Polycystic ovary syndrome.

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

“…On the other hand, LH is probably produced to a lesser extent following a decrease in androgens, reducing the dominant effect of LH on FSH. In addition, Nigella sativa extract may reduce LH dominance over FSH by inhibiting nitric oxide and leptin‐releasing neurons that are directly involved in the synthesis of LH from the anterior pituitary gland, thereby increasing ovulation in women with PCOS (Eini et al, 2020 ). A study by Parhizkar et al.…”

“…On the other hand, LH is probably produced to a lesser extent following a decrease in androgens, reducing the dominant effect of LH on FSH. In addition, Nigella sativa extract may reduce LH dominance over FSH by inhibiting nitric oxide and leptin-releasing neurons that are directly involved in the synthesis of LH from the anterior pituitary gland, thereby increasing ovulation in women with PCOS (Eini et al, 2020). A study by Parhizkar et al (2016) on the ovariectomized rats treated with N. sativa extract showed that the extract of this plant, in a dose-dependent manner (300 to 1200 mg/kg), reduced menopausal symptoms including uterine weight/edema loss and decreased serum estradiol level and the number of inflammatory cells in the vagina compared with the control group (Parhizkar et al, 2016).…”

A Review of Clinical and Preclinical Studies on the Therapeutic Potential of Black Seeds (Nigella sativa) in the Management of Polycystic Ovarian Syndrome (PCOS)

“…Significant improvements in maturation, fertilization, and blastocyst formation were observed in the oocytes of dehydroepiandrosterone-induced PCOS mice after the administration of 50 g/mL of a hydro-alcoholic extract of N. sativa. The N. sativa treatment also increased the glutathione concentration and glutathione peroxidase mRNA expression in oocytes [37]. Moreover, an experimental animal study demonstrated that the administration of 300 mg/kg of a hydro-alcoholic extract of N. sativa + 1,200 mg/kg of honey or 600 mg/kg of a hydro-alco-Table 2.…”

“…Animal study (dehydroepiandrosterone-induced PCOS mice) [37] • Significant improvements in maturation, fertilization, and blastocyst formation.…”

A review of the effect of fertility agents (Herbs and drugs) on the hypothalamus

“…There are evidence that the extract derived from Nigella sativa, owing to its rich content of phytoestrogenic and flavonoid compounds, is effective in reducing ovarian cyst formation induced by exposure to estradiol valerate, letrozole, and dehydroepiandrosterone in diverse animal models used to simulate PCOS (Khani et al, 2021;Eini et al, 2020).…”