Reproductive senescence is accompanied by a reduced number and quality of ovarian follicles in response to the accumulation of free radicals and the process of apoptosis. Having selected mice as models, we examined the hypothesis that curcumin as an antioxidant and anti-inflammatory agent might prevent or retard ovarian aging. Female NMRI 21-day-old mice were divided into control, vehicle and curcumin groups. In the treatment group the mice received curcumin at 100mgkg–1day–1 intraperitoneally. After 6, 12 and 33 weeks several parameters were examined including ovarian reserve, oocyte quality, oxidative status, invitro fertilisation and expression of ovulation-related (growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15)) and anti-aging-related (sirtuin 1 (SIRT-1) and SIRT-3) genes. Curcumin treatment up to 12 and 33 weeks resulted in increased ovarian volume and number of follicles and was associated with elevated anti-Müllerian hormone and oestrogen and diminished FSH serum levels. Furthermore, enhanced oocyte maturation, fertilisation and embryo development plus reduced oxidative stress were seen in the curcumin group. Also, the expression of GDF-9, BMP-15, SIRT-1 and SIRT-3 genes was increased in the curcumin group. Concerning gestational age, the findings of the study suggested that administration of curcumin could delay the process of oocyte aging in a mouse model.
Although in‐vitro maturation (IVM) of oocytes has been presented as an alternative treatment to traditional stimulated in‐vitro fertilization, the culture condition can be improved by natural antioxidants. Thus, we investigated the protective effect of Thymoquinone (TQ) during IVM in the polycystic ovary syndrome (PCOS) mice model. The induction of PCOS was made by dehydroepiandrosterone via subcutaneous injection, in prepubertal female B6D2F1‐mice. After 21 days later, germinal vesicle (GV)‐stage‐oocytes were extracted and incubated in IVM media containing 0, 1.0, 10.0, and 100.0 μM of TQ. To assess fertilization and blastulation rates, after 22–24 hr, the treated oocytes were fertilized in‐vitro with epididymal spermatozoa. Some other oocytes were evaluated for maturation, epigenetic, and oxidative stress markers.
Similarly, the mRNA expression of epigenetic enzymes genes (Dnmt1 and Hdac1), three maternally derived genes (Mapk, CyclinB, and Cdk1) and apoptosis‐related genes (Bax and Bcl2) were assessed. Our results showed that the maturation, fertilization, and blastulation rates were significantly higher in the 10.0 μM TQ‐treated group compared with the untreated group and likewise with in‐vivo matured oocytes. The Bax expression was reduced in 10.0 μM TQ matured oocytes, but Bcl2, Dnmt1, Hdac1, Cdk1, and Mapk were upregulated in this group compared to other groups. Furthermore, dimethylation of histone‐3 at lysine‐9 (H3K9m2) and DNA methylation were significantly increased whereas H4K12 acetylation (H4K12ac) was decreased in the 10.0 μM TQ‐treated group in comparison with control and in‐vivo matured oocytes. Therefore, our results are suggesting that 10.0 μM TQ may enhance the developmental competence of PCOS oocytes via the modulation of oxidative stress and epigenetic alterations.
Endometriosis, a chronic inflammatory disease, is identified by the presence of endometrial tissue outside the uterus. The prevalence of this disease among reproductive-age women is almost 10–15%. High levels of IL-6 and IL-8 have been found in the peritoneal fluid (PF) of women with endometriosis and are involved in its pathogenesis. Isolated stromal cells from 12 ectopic and eutopic endometrial biopsies of women with ovarian endometrioma and also 12 endometrial biopsies of nonendometriotic controls were treated with 1.1 µM pyrvinium pamoate, a Wnt/β-catenin signaling pathway inhibitor, for 72 hrs. Before treatment, mRNA gene expression and secretion of IL-6 and IL-8 were significantly higher in ectopic (EESCs) than eutopic (EuESCs) and control (CESCs) endometrial stromal cells. After treatment, mRNA gene expression and also secretion of IL-6 and IL-8 were significantly reduced. Our Findings showed that pyrvinium pamoate suppresses the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells. Additional investigations on this compound are required before clinical application.
Background
Alteration of free radicals (reactive oxygen species) causes mammals' sperm damage. Gallic acid (GA) is known as an antioxidant which is effective against oxidative stress. The purpose of this study was to evaluate the antioxidant effects of GA on the sperm apoptosis and in vitro fertilization (IVF) in adult male mice treated with cyclophosphamide (CP).
Materials and Methods
Following a pilot study to find the dose responses of GA, 40 adult male naval medical research institute (NMRI) mice (32 ± 3 g) were divided into five groups (n = 8): control, sham (normal saline, NS: 0.2 mL per day), CP (15 mg kg–1 per week; intraperitoneal, IP), GA (12.5 mg kg
–1 per day; IP), and GA+CP. After the treatment, sperm parameters were analyzed. The apoptosis of sperm was measured by Annexin‐PI staining method followed by flow cytometry detection. Fertility was assessed by IVF method among the groups.
Results
The difference in sperm parameter and fertility rate between the control (% 80.05 ± 6.53) and cyclophosphomide groups (% 51.82 ± 10.78) was significant (P < .001) but GA plus CP (% 78.16 ± 5.71) restored the fertilization rate (P < .001).
Also, a remarkable increase was noted regarding apoptotic sperm in CP group vs the control group. The comparison in the five groups shows that GA cotreatment was significantly effective in reducing the apoptosis rate caused by cyclophosphamide (P < .05).
Conclusion
It was ultimately attained that GA has a potent antioxidant effect which could inhibit the detrimental effect of CP on the apoptosis and fertility rate of sperm in the mouse.
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