Ovarian Tissue Damage Research Articles

Protective Effect of Bio-Scaffold Against Vitrification Damage in Mouse Ovarian Tissue.

Ovarian tissue cryopreservation is regarded as useful method for fertility preservation. This study aimed to preserve most of the follicular reserve from the destructive effects of cryoprotectant solutions and liquid nitrogen. For this purpose, 48 female NMRI mice (8 weeks old) were randomly divided into six groups: Fresh (not vitrified), Vitrification (not encapsulated), Alginate 1 (encapsulated in 1% alginate hydrogel before placing in vitrification solutions), Alginate 2 (encapsulated in 1% alginate hydrogel before placing in liquid nitrogen), Aloe vera 1 (encapsulated in Aloe vera pieces before placing in vitrification solutions), Aloe vera 2 (encapsulated in Aloe vera pieces before placing in liquid nitrogen). After vitrification and warming, the histological evaluation showed that the average number of intact primordial follicles decreased significantly in all groups compared to the Fresh group. (P < 0.05). Results of evaluating the expression of apoptosis-related genes showed that the ratio of Bax/Bcl2 and P53 significantly decreased in the Alginate 2 group compared with the vitrification group. The level of Kit gene (KIT proto-oncogeni receptor tyrosine kinase gene) expression was either the same or lower in the experimental groups than in the vitrification group, but there was no statistically significant difference. Levels of tissue nitric oxide (NO) and malondialdehyde (MDA) in Alginate groups 1 and 2 showed a significant decrease compared with the vitrification group (P < 0.05). To conclude, Encapsulation of ovaries in 1% alginate hydrogel before immersion in liquid nitrogen may reduce the damage caused by cryopreservation.

The Role of Mannitol and Vitamin D in Ovarian Ischemia/Reperfusion Injury in Rats with Acute Abdominal.

This study was designed to investigate the effects of vitamin D and mannitol in an experimental rat ovarian torsion model. Thirty-two female Wistar albino rats were randomly classified as group 1: (sham), group 2: (detorsion), group 3: (detorsion + mannitol), group 4: (detorsion + vitamin D) and group 5: (detorsion + mannitol + vitamin D) (for each group n = 8). All groups were subjected to bilateral adnexal torsion for 2 h except for group 1. Bilateral adnexal detorsion was performed in all groups except for group 1. Groups 3 and 5 intraperitoneally received the injection of mannitol at a dose of 0.3 mg/kg 30 min before detorsion. Also, the group's 4 and 5 orally received vitamin D in a dose of 500 IU/kg/day for two weeks before torsion. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and proliferating cell nuclear antigen (PCNA) levels were analyzed. According to the histopathological analyses, ovarian tissue damage and follicle counting were evaluated. TOS, OSI and histopathologic score values of ovarian tissue were significantly lower in group 5 than groups 2, 3 and 4 (p < 0.05). The PCNA level was significantly higher in group 5 than in groups 2, 3 and 4 (p < 0.05). A strong negative correlation was found between OSI and PCNA in groups 2, 3, 4 and 5 (r = -0.92, p = 0.01; r = -0.98, p < 0.0001; r = -0.98, p < 0.0001 and r = -0.96, p = 0.0002, respectively). The numbers of primordial follicles in group 5 (p < 0.001) and primary follicles in group 4 (p < 0.001) were significantly higher when compared to group 2. Based on the results of this study, it could be suggested that combination treatment of mannitol with vitamin D is more effective in reversing tissue damage induced by ischemia-reperfusion (I/R) injury in the ovarian torsion model than administration of only an agent.

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress

ObjectiveHepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. MethodsMice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. ResultsOvarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. ConclusionFerroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; 22(4): 494–503.

Therapeutic potential of probiotics to counter Campylobacter infections: An In vitro and In vivo evaluation in mice

Probiotics, including Lactic Acid Bacteria (LAB), have gained considerable attention due to their potential health benefits for humans and animal livestock. This research aimed to isolate probiotic bacteria of human origin and explore their therapeutic potential against Campylobacter strains, which are recognized as the leading bacterial cause of human gastroenteritis worldwide. A collection of 230 LAB isolates from human stools were screened for the ability of cell free supernatants to inhibit the growth of three strains of C. jejuni and a C. coli. Co-culture and agar-well diffusion assays identified seven isolates with inhibitory activity against Campylobacter ssp., which were characterized as probiotic strains by their tolerance to pH 2 and bile salts, and then identified as Enterococcus spp. using 16S rRNA gene sequencing E. faecalis NM231, E. faecium NM234, E. faecium NM233, E. faecium NM113, E. durans NM232, E. faecalis NM235, and E. faecium NM236. In vivo evaluation was undertaken by the oral administration of selected probiotics to groups of mice prior to challenge with C. jejuni. Histopathological examinations showed challenge groups receiving either mixed probiotics or E. faecium NM234 were protected against C. jejuni-induced jejunal, colonic, ovarian and uterine tissue damage. Immunohistochemical detection of the challenged mice revealed the presence of C. jejuni antigen in jejunal, colonic, ovarian and uterine sections but was absent in mice receiving either mixed probiotics or E. faecium NM234. This study introduces E. faecium NM234 as a promising probiotic against Campylobacter.

Apoptotic Pathways and Anti-Müllerian Hormone affects the Ovarian Tissue Damage during Endometrioma Cystectomy

Apoptotic Pathways and Anti-Müllerian Hormone affects the Ovarian Tissue Damage during Endometrioma Cystectomy

Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats

It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.

Ovarian cauterization versus Cacl2 Injection For "In Situ Ovariectomy" In Female Cats

Overpopulation of stray and unwanted cats has been a serious issue in every country and different individuals have different motivations for their spaying or neutering. The current experiment aimed to evaluate the feasibility and safety of ovarian cauterization compared to CaCl2 injection for ovarian tissue damage in female cats. Each ovary of three cycling normal cats in reproductive age was punctured at four sites and 40 W was applied to 5 seconds at each point using monopolar electro-coagulation, resulting in 800 J (Joules) of thermal energy. Ovaries of another three cats were injected with 0.25 ml of 20% CaCl2 in 95% ethanol solution. Macroscopic and microscopic lesions were assessed depending on a number of evaluating criteria. Operative time, intraoperative and postoperative complications, and estrogen level estimation showed significant difference between both techniques. The cauterization technique proved easy applicable and safe, and there were no intra-abdominal thermal injuries. Histologic evaluation proved essential to clarify the ovarian functional activity. Ovarian cauterization seems to be feasible and safe, and 40 W (800 J) thermal energy allowed incomplete ovarian thermal damage.

Comparative effects of a calcium chelator (BAPTA-AM) and melatonin on cryopreservation-induced oxidative stress and damage in ovarian tissue

Oncology treatments cause infertility, and ovarian tissue cryopreservation and transplantation (OTCT) is the only option for fertility preservation in prepubertal girls with cancer. However, OTCT is associated with massive follicle loss. Here, we aimed to determine the effect of supplementation of slow freezing and vitrification media with BAPTA-AM and melatonin alone and in combination on ovarian tissue viability, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), and follicular morphology and viability. Our results indicated that BAPTA-AM and melatonin can significantly improve ovarian tissue viability and the TAC/ROS ratio and reduce ROS generation in frozen-thawed ovarian tissues in slow freezing and vitrification procedures. BAPTA-AM was also found to be less effective on TAC compared to melatonin in vitrified ovarian tissue. While supplementation of slow freezing and vitrification media with BAPTA-AM and/or melatonin could increase the percentage of morphologically intact follicles in cryopreserved ovarian tissues, the differences were not significant. In conclusion, supplementation of cryopreservation media with BAPTA-AM or melatonin improved the outcome of ovarian tissue cryopreservation in both vitrification and slow freezing methods. Our data provide some insight into the importance of modulating redox balance and intracellular Ca2+ levels during ovarian tissue cryopreservation to optimize the current cryopreservation methods.

Retracted: Cryptotanshinone Protects against PCOS-Induced Damage of Ovarian Tissue via Regulating Oxidative Stress, Mitochondrial Membrane Potential, Inflammation, and Apoptosis via Regulating Ferroptosis.

[This retracts the article DOI: 10.1155/2022/8011850.].

Effect of direct therapeutic ultrasound exposure of ovaries on histopathology, inflammatory response, and oxidative stress in dogs

BackgroundThis research was designed to evaluate the effects of therapeutic ultrasound waves on ovarian germinal tissue and inflammatory cytokines (interleukin-6 (IL-6), IL1β, tumor necrosis factor-α (TNF-α)), acute phase proteins (serum amyloid A (SAA), C reactive protein (CRP)) and oxidative stress (total antioxidant capacity (TAC), and malondialdehyde (MDA)) in dogs. Twenty-six clinically healthy adult mix-breed female dogs were aligned into three groups. Laparotomy was performed in control (n = 6) and treatment (T5, n = 10; T10, n = 10) groups. The ultrasonic exposure of ovaries in treatment groups was performed during laparotomy by round motions of the therapeutic ultrasonic transducer on both ovaries (1 MHz frequency, 1.5 W⁄cm2) for 5 min in the T5 group and for 10 min in the T10 group. Blood samples were collected from the jugular vein into a plain glass tube on days 0 (before laparotomy), 3, 6, and 9 after surgery. All control and treatment groups’ dogs were ovariectomized for histological evaluation on day 60 after laparotomy or laparotomy + ultrasound exposure.ResultsDirect exposure of ovaries with therapeutic ultrasound waves induced inflammation and oxidative stress comparison with the control group. Histopathological evaluation of treated ovaries with ultrasound waves indicated a decreased number of primordial follicles (ovarian reserve) and oocyte preservation scores compared with ovaries in the control group.ConclusionsThese changes may cause subfertility in the long term. It seems that inflammatory response and oxidative stress are factors in the permanent damage of ovarian tissue.

Lyophilized equine platelet-rich plasma (L-GFequina) antagonize the Reproductive toxicity and oxidative stress Induced by Cyclophosphamide in female rats

BackgroundThe antineoplastic agent Cyclophosphamide (CP) induces reproductive toxicity. New strategies for protecting ovarian tissue damage in women with chemotherapy-induced reproductive toxicity are essential. This study was designed to evaluate the possible protective effect of combined treatment with L-GFequina on CP-induced reproductive toxicity in the mature female rat.MethodologyForty mature female rats were assigned into four groups: First group, control: rats were intraperitoneally injected (IP) with 200 µl sterile saline solution on days 1 and 10; Group 2 (CP): were IP injected with 75 mg/kg on days 1 and 10 to induce POI); Group 3 (CP + L-GFequina): as in group 2 + IP injected with 200 µl rehydrated L-GFequina half-hour after CP injection on day 1 and 10); Group 4 (L-GFequina): rats were IP injected with 200 µl L-GFequina on day 1 and 10). Blood samples were collected for a complete blood picture and determinations of nitric oxide and malondialdehyde. Animals were sacrificed on Day-21, and genitalia was dissected, weighed, and fixed in 10% formalin for histopathological and morphometric evaluation.ResultsOn day 21 of the experiment, body weight, ovarian parameters (Ovarian weight, uterine weight, the number of ovarian follicles, and corpora lutea (CL) were determined, and histopathological changes, blood profile, as well as antioxidant activity assessment, were performed. CP significantly suppresses ovarian and uterine functions and increased MAD, NO levels, RBCs, hemoglobin, WBCs, and platelet count compared to the control group ( P < 0.05). While, in CP + L-GFequina group, gross, histomorphometry parameters, blood, and biochemical markers were similar to that in the control. IP injection of L-GFequina alone significantly (P < 0.05) increased body weight, and ovarian and uterine morphometry compared with the control.Conclusionco-administration of L-GFequina with CP might protect the reproductive organs in rats through its high antioxidant capacity.

The effect of Nateglinide and Octreotide on follicular morphology and free radical scavenging system in letrazole-induced rat model of PCOS.

To investigate the effects of octreotide and nateglinide on ovarian follicle count, ovarian tissue damage, biochemical parameters and free radical scavenging system in letrazole-induced rat model of PCOS. Forty-two female Sprague-Dawley rats were divided into six groups. Group 1 (Control Group): after localizing the ovaries and the uterine horns, the abdominal wall was closed without any surgical procedure. Group 2 (PCOS Group): PCOS was induced by administrating Letrozole orally for 21 successive days. At the end of 21 days, rats underwent ovarian biopsies. The experimental PCOS model was considered successful in the presence of atretic follicles without granulosa cell stratification. Group 3 (PCOS + Nateglinide Group): Nateglinide was administered by oral dropper for 30 days to the rats in which PCOS model was created. Group 4 (Nateglinid only Group): 30 days of NG was applied to the rats without PCOS. Group 5 (PCOS+Octreotide Group): 0.1 mg/kg/day Octreotide was given intraperitoneally for 4 weeks to the rats in which PCOS model was created. Group 6 (Octreotide only Group): animals without PCOS given 0.1 mg/kg/day Octreotide at the end of the treatment, bilateral oophorectomy was performed and blood samples were collected from all groups. Ovarian tissue was stained immunohistochemically with TLR-4 in addition to conventional staining. In addition to follicle classification, ovarian damage was graded. Serum insulin, FSH and LH, TNF-α, IL-6, SHBG, SOD, IGF-1, MDA and GSH levels were also measured. The cystic and degenerated follicle density of PCOS group was high compared with the other groups. Both cystic and degenerated follicles were significantly reduced in PCOS+NG and PCOS+OC groups compared to PCOS group. There was no difference between the groups in terms of serum LH, FSH and insulin levels (p>0.05). Serum testosterone level was significantly higher in the PCOS group compared to the other groups (p<0.01). Adding OC or NG to PCOS groups did not cause significant changes in testosterone levels. TNF-α and IL-6 levels were high in PCOS group (p<0.03). IGF-1 and MDA levels were higher in PCOS than in other groups (p<0.03, p<0.01 respectively). Adding OC or NG to the treatment normalized IGF-1 and MDA levels. Serum GSH levels were significantly lower in the PCOS group (p<0.05). Adding NG to the treatment increased GSH levels. Both NG and OCT reverses atretic and degenerate follicle damage due to PCOS through TLR-4, antioxidant and anti-inflammatory pathways.

Calcium chloride diluted in ethanol 95% as female sterilizing agent: effect of transcutaneous delivery in rats

BackgroundDifferent fertility control methods are investigated as a tool for population control of free-roaming animals. Chemical castration using calcium chloride has been widely studied over the years in males, but there are few studies related to its use in females. Therefore, we aimed to evaluate the local effects, as a potential chemosterilant, of two concentrations of calcium chloride diluted in 95% ethanol when administered by transcutaneous ultrasound-guided intraovarian injection in rats. In this study, 30 female Wistar rats were randomly divided into three treatment groups, which consisted of transcutaneous ultrasound-guided intraovarian injection of: 0.9% sodium chloride solution (GC); 10% calcium chloride diluted in 95% ethanol (G10); 20% calcium chloride diluted in 95% ethanol (G20). The animals were subdivided into two evaluation times, 15 days (n = 5 of each group) and 30 days (n = 5 of each group) after the intraovarian injection. The ovarian diameter was measured using ultrasound image prior and immediately after the injection and after the treatment period. Furthermore, animals’ clinical evaluation, estrous cycles assessment, macroscopic examination of the abdominal cavity and histological evaluation of the ovaries were performed.ResultsOvarian ultrasound measurement revealed changes (p < 0.05) between ovarian diameters before and immediately after the injection in all treatments. Three animals in G20 had a small focal skin lesion at the injection site that evolved to total healing. Extended and abnormal estrous cycles were observed in G10 and G20. At gross examination, adhesions and ovarian cysts were noticed in both groups, G10 and G20. Also, the histopathology analysis revealed changes in ovarian architecture and vessel congestion in G10 and G20, but ovarian tissue damage was greater in the ovaries treated with the highest concentration (G20).ConclusionsThe results indicate that 20% calcium chloride diluted in 95% ethanol may be a potential agent for inducing sterilization in females and was possible to be minimally invasively delivered.

Widening the Lens on Prothioconazole and Its Metabolite Prothioconazole-Desthio: Aryl Hydrocarbon Receptor-Mediated Reproductive Disorders through in Vivo, in Vitro, and in Silico Studies.

Reproductive disorders are a serious public health problem worldwide. Epidemiological data suggest that exposure to environmental pollutants is associated with the onset of reproductive disorders. However, the effects in reproductive health and exact mechanism of action of representative agricultural compounds prothioconazole (PTC) and its metabolite prothioconazole-desthio (dPTC) on mammals remain unclear. Here, we studied the physiological effects of the exposure to environmentally relevant doses of PTC and dPTC in mice reproductive systems. Combining in vivo, in vitro, and in silico studies, we observed that PTC and dPTC disrupt reproductive health by inducing metabolic perturbation, induction of apoptosis, and inflammation in gonadal tissue, which are achieved via activation of the aryl hydrocarbon receptor (AhR). Convincingly, the addition of alternate-day injections of CH223191 (an AhR inhibitor) to the 30-day exposure regimen ameliorated ovarian tissue damage, as evidenced by decreased TUNEL-positive cells and partially restored the inflammation and apoptotic factor levels. This study comprehensively reports the toxic effects of low-dose PTC and dPTC in the reproductive system in vivo and identifies AhR as a potential therapeutic target for the amelioration of reproductive disorders caused by similar endocrine-disrupting chemicals.

Lycium barbarum polysaccharides regulate AMPK/Sirt autophagy pathway to delay D-gal-induced premature ovarian failure

This study aims to explore the molecular mechanism of Lycium barbarum polysaccharides(LBP) in alleviating premature ovarian failure(POF) in mice via the 5'-adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(Sirt1) signaling pathway. The POF mouse model was established by D-galactose(D-gal) injection at the back. Six groups were set up, including a normal control group, a model group, a LBP group, a 3-MA(autophagy inhibitor 3-methyladenine) group, an AMPK inhibitor group, and a LBPAMPK inhibitor group, with 15 mice in each group. After 28 continuous days of administration, enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of sex hormones [estradiol(E_2), luteinizing hormone(LH), and follicle-stimulating hormone(FSH)] in serum. The ovarian mass coefficient was measured. Senescence-associated β-Galactosidase(SA-β-Gal) staining and hematoxylin-eosin(HE) staining were performed for observing the state of ovarian senescence and the morphological changes of the ovary. Immunohistochemical method was used to measure the expression of the autophagy marker LC3-Ⅱ in ovarian tissue. Western blot was employed to measure the expression levels of the senescence marker p16~(INK4 a), autophagy markers(LC3-Ⅱ and Beclin-1), the autophagy substrate p62, lysosome-associated membrane protein 2(LAMP2), and the proteins in the AMPK/Sirt1 pathway and mammalian target of rapamycin complex 1(mTORC1)/UNC-51-like kinase 1 Ser757 site(Ulk1 Ser757) pathway. Compared with the normal control group, the modeling of POF decreased the ovarian granulosa cells and follicles, led to the ovarian aging and severe sex hormone secretion disorders, weakened ovarian autophagy activity, and down-regulated the expression of proteins in the AMPK/Sirt1 pathway(P&lt;0.05). Compared with the model group, the treatment with LBP increased ovarian granulosa cells and follicles, alleviated aging and sex hormone disorders, increased autophagy activity, and activated the AMPK/Sirt1 pathway(P&lt;0.05). Both 3-MA and AMPK inhibitor can inhibit autophagy and aggravate ovarian damage and aging in mice. AMPK inhibitor can partially attenuate the role of LBP in promoting autophagy activation and alleviating aging and ovarian tissue damage(P&lt;0.05). LBP can alleviate the symptoms of POF induced by D-gal by promoting the activation of AMPK/Sirt1 pathway.

Epigallocatechin-3-gallate attenuates cyclophosphamide-induced damage in mouse ovarian tissue via suppressing inflammation, apoptosis, and expression of phosphorylated Akt, FOXO3a and rpS6

This study was conducted to evaluate the protective effects of epigallocatechin-3-gallate (EGCG) against ovarian toxicity in cyclophosphamide-treated mice and to verify the possible involvement of phosphorylated Akt, FOXO3a and rpS6 in the EGCG actions. Mice received saline solution (i.p.; control) or a single dose of cyclophosphamide (200 mg/kg body weight, i.p.) or mice were pretreated with N-acetylcysteine (150 mg/kg body weight, i.p.; positive control) or with EGCG (5, 25 or 50 mg/kg body weight, i.p.) once daily for three days followed by injection with single dose of cyclophosphamide (200 mg/kg body weight, i.p.). Thereafter, the mice were euthanized, and the ovaries were harvested and destined to histological (follicular morphology and activation), immunohistochemistry (cleaved caspase-3 and TNF-α) and fluorescence (mitochondrial activity and GSH concentrations) analyses. Furthermore, we examined the participation of p-Akt, p-FOXO3a and p-rpS6 in the protective effects of EGCG in cyclophosphamide-induced ovarian damage by immunohistochemical staining. The results showed that pretreatment with N-acetylcysteine or EGCG at 25 and 50 mg/kg before cyclophosphamide administration preserved the normal follicular morphology, prevented primordial follicle loss, reduced atresia, inflammation, and mitochondrial damage, and increased GSH concentrations compared to the only cyclophosphamide treatment. Additionally, pretreatment with 25 mg/kg EGCG regulated phosphorylated Akt, FOXO3a and rpS6 after cyclophosphamide treatment. In conclusion, short-time pretreatment with 25 mg/kg EGCG can prevent follicle loss in cyclophosphamide-treated mice by reducing oxidative damage, inflammation, and apoptosis, and regulating of p-Akt, p-FOXO3a and p-rpS6.

The effects of amiodarone in ovarian injury due to oxidative stress and inflammation caused by ischemia-reperfusion

Objective Ovarian ischemia constitutes 2–3% of all gynecological emergencies. New-generation therapeutic agents need to be discovered, in addition to invasive interventions capable of reducing the risk of potential ovarian ischemia to a minimum and protecting against potential adverse outcomes. Aims To investigate the effects of amiodarone (AMD) on ischemia-reperfusion-induced oxidative stress and inflammation-induced ovarian damage. Methods The control group, received intraperitoneal (i.p.) injection of saline solution. The ischemia group (I-Group), was subjected to ischemia-induced injury without drug administration. The ischemia + AMD (50 mg/kg) group was subjected to ischemia injury and also received i.p. 50 mg/kg AMD prior to induction of ovarian ischemia. The ischemia–reperfusion (I/R group) was exposed to ischemia and reperfusion-induced injury without drug administration. The I/R + AMD (50 mg/kg) group underwent I/R injury together with i.p. administration of 50 mg/kg AMD prior to induction of ovarian I/R. The Sham + AMD group received intraperitoneal (i.p.) injection of 50 mg/kg AMD alone. In this study performed thiobarbituric acid reactive substances (TBARS), thiol (−SH), interleukin 1 Beta (IL-1β), interleukin 6 (IL-6), toll-like receptor 4 (TLR4) and nuclear factor-kappa B(NF-κβ). Results Increased oxidative stress and inflammation as a result of ovarian I and I/R application activated the cascade. AMD was not sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-kβ, which were up-regulated by triggering oxidative stress and inflammation, were not regressed by the effects of AMD. Conclusions AMD, used as an antiarrhythmic agent, was found to be insufficient, despite its antioxidant and anti-inflammatory properties, to reduce the experimentally induced ovarian tissue damage.

Fertility Sparing Procedure using Carbon Dioxide Fiber Laser Vaporization of Ovarian Endometrioma.

The surgical management of endometrioma is still a matter of debate. Cystectomy, which is recognized as the standard technique, seems to be associated with a potential reduction in the ovarian reserve due to the inadvertent removal and thermal damage of healthy ovarian tissue. New ablative techniques with reduced tissue penetration depth and less thermal spread to the surrounding parenchyma may represent a viable alternative to cystectomy. For these reasons, the aim of this manuscript is to demonstrate the ablation of the endometrioma capsule using a CO2 fiber laser technique and discuss the clinical outcomes. Once the cyst has been drained and washed, a biopsy is taken. After cyst eversion, vaporization of the inner surface of the cyst is performed using a CO2 fiber laser. The technique is simple and reproducible as even young surgeons without any surgical experience were more confident in performing laser CO2 vaporization instead of cystectomy. The positive effects of CO2 technology are reported in a randomized controlled trial, where the postoperative changes in the antral follicular count (AFC) and antimullerian hormone (AMH) levels were compared between patients who had their endometrioma excised (cystectomy) and those who had undergone endometrioma vaporization with CO2 laser. The patients treated with CO2 laser showed significantly increased AFC without a reduction in serum AMH levels as compared to the cystectomy group, in which both parameters were significantly reduced. The postoperative pregnancy rate was also assessed, and comparable pregnancy rates were found after both treatments. On the contrary, patients treated with the CO2 fiber laser technique had more favorable in-vitro fertilization (IVF) outcomes compared to cystectomy. In conclusion, the CO2 fiber laser technique may represent a viable alternative to cystectomy in the surgical treatment of endometrioma in terms of ovarian preservation, pregnancy rates, and IVF outcomes. Moreover, it has the advantage of being independent of the surgeon's skills and personal experience.

Ovarian suspension loop: an assembled device for ovarian lifting and immobilization during laparoscopic cystectomy

The mobility and smooth surface of the ovaries can pose a challenge during laparoscopic cystectomy, with difficulties in manipulation and visualization. We describe assembling a device for ovarian lifting and immobilization that utilizes a nylon suture and a “scalp vein set” to create a loop. The loop can be passed into the pelvic cavity and then slid beneath the ovary, elevating and stabilizing it during surgery without the need to puncture the ovarian tissue or grabbing and damage the utero-ovarian infundibulopelvic ligaments. This device is inexpensive, and its components are easily accessible. This assembled device prevents repetitive falling of the ovary into the pelvic cavity, facilitates laparoscopic ovarian cystectomy, and saves operative time.

Cryptotanshinone Protects against PCOS-Induced Damage of Ovarian Tissue via Regulating Oxidative Stress, Mitochondrial Membrane Potential, Inflammation, and Apoptosis via Regulating Ferroptosis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. Cryptotanshinone (CRY) has been shown to be effective in reversing reproductive disorders, but whether it can be used in the treatment of polycystic ovary syndrome remains unclear. We aimed to explore whether the mechanism of cryptotanshinone (CRY) in the treatment of polycystic ovary syndrome (PCOS) can be driven via regulating ferroptosis. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. An in vitro model of ischemia-reperfusion (IR) of granulosa cells was established. The in vitro and rat models of PCOS were subjected to different treatments including ferroptosis activators and inhibitors, CRY, and MAPK inhibitor. Oxidative stress was evaluated by measuring the activities of SOD, MDA, and GSH-PX. Total body weight and ovarian weight, as well as the levels of LH and the LH to FSH ratio, significantly increased in rats with PCOS, compared with controls. The expression of Bax was increased in PCOS tissues while PGC1α, NFR1, GPX4, catalase p-ERK, and Bcl-2 were all downregulated. Ferroptosis activator, erastin, had effects similar to those of PCOS while the contrary was found with CRY and ferroptosis inhibitor treatment groups. In vitro, CRY inhibited oxidative stress, MMP, and NF-κB and activated MAPK/ERK signaling by regulating ferroptosis. Overall, this study indicated that CRY protects against PCOS-induced damage of the ovarian tissue, via regulating oxidative stress, MMP, inflammation, and apoptosis via regulating ferroptosis.