Efficacy of acupuncture in animal models of various ovarian dysfunctions: a systematic review and meta-analysis.

Objective: This study aims to assess the comprehensive and integrated modulatory effects of acupuncture and electroacupuncture on various ovarian dysfunctions. Methods: We systematically searched for articles on animal experiments related to polycystic ovary syndrome (PCOS), premature ovarian failure (POF), premature ovarian insufficiency (POI), and perimenopausal syndrome (PMS) across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and four Chinese language databases. The search covered the period from inception to November 2023. We conducted a comparative analysis between the acupuncture group and the model group (untreated) based on eligible literature. Our primary outcomes encompassed serum sex hormones (Luteinizing hormone, Follicle-stimulating hormone, Testosterone, Estradiol, Progesterone, and Anti-Müllerian hormone) and ovarian weight. Dichotomous data were synthesized to establish the relative risk (RR) of notable post-treatment improvement, while continuous data were pooled to determine the standardized mean difference (SMD) in post-treatment scores between the groups. Statistical analyses, including sensitivity analysis, Egger's test, and the trim-and-fill method, were executed using Stata 15.0 software. Results: The meta-analysis encompassed 29 articles involving a total of 623 rats. In comparison to rat models of PCOS, the experimental group exhibited a reduction in serum levels of LH, T and LH/FSH ratio. However, no statistically significant differences were observed in AMH, FSH, E2 levels, and ovarian weight between the two groups. In the ovarian hypoplasia model rats, both acupuncture and electroacupuncture interventions were associated with an increase in E2 levels. However, the levels of LH and FSH did not exhibit a significant difference between the two groups. Conclusions: Acupuncture or electroacupuncture facilitates the restoration of ovarian function primarily through the modulation of serum sex hormones, exerting regulatory effects across various types of ovarian dysfunction disorders. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316279.

[Effect of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on PI3K/AKT/FOXO3a pathway in mice with poor ovarian response].

OBJECTIVE: To observe the protective effect of acupuncture at "Zhibian" (BL 54) through "Shuidao (ST 28)" based on the PI3K/AKT/FOXO3a pathway in mice with poor ovarian response (POR), and to explore the possible mechanism of acupuncture in inhibiting ovarian granulosa cells apoptosis in POR. METHODS: A total of 45 mice with regular estrous cycles were randomly divided into a blank group, a model group and an acupuncture group, with 15 mice in each group. Mice in the model group and the acupuncture group were given triptolide suspension (50 mg•kg-1•d-1) by gavage for 2 weeks to establish POR model. After successful modeling, mice in the acupuncture group were given acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) for 2 weeks, once a day, 20 min each time. Ovulation induction was started the day after the intervention ended, and samples were taken from each group after ovulation induction. Vaginal smears were used to observe changes in the estrous cycle of mice. The number of oocytes retrieved, ovarian wet weight, final body weight, and ovarian index were measured. The levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) in serum were detected by ELISA. The morphology of ovarian tissue was observed by HE staining. The apoptosis of ovarian granulosa cells was detected by TUNEL staining. The mRNA expression of PI3K, AKT, and FOXO3a in ovarian tissue was detected by real-time fluorescence quantitative PCR. The protein expression of Bcl-2 associated X protein (BAX), caspase-3, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) in ovarian tissue was detected by Western blot. RESULTS: Compared with the blank group, the rate of estrous cycle disorder in the model group was increased (P<0.01); compared with the model group, the rate of estrous cycle disorder in the acupuncture group was decreased (P<0.01). Compared with the blank group, the number of oocytes retrieved, ovarian wet weight, ovarian index, and final body weight in the model group were decreased (P<0.01); compared with the model group, the number of oocytes retrieved, ovarian index, and ovarian wet weight were increased (P<0.01, P<0.05), and there was no significant difference in final body weight (P>0.05) in the acupuncture group. Compared with the blank group, the serum levels of FSH and LH were increased (P<0.01), and the serum levels of AMH and E2 were decreased (P<0.01) in the model group; compared with the model group, the serum levels of FSH and LH were decreased (P<0.01, P<0.05), and the serum levels of AMH and E2 were increased (P<0.01, P<0.05) in the acupuncture group. Compared with the blank group, the number of normal developing follicles in ovarian tissue in the model group was decreased and the morphology was poor, while the number of atretic follicles increased; compared with the model group, the number, morphology, and granulosa cell structure of follicles in the acupuncture group improved to varying degrees, and the number of atretic follicles decreased. Compared with the blank group, the apoptosis rate of ovarian granulosa cells in the model group was increased (P<0.01); compared with the model group, the apoptosis rate of ovarian granulosa cells in the acupuncture group was decreased (P<0.01). Compared with the blank group, the FOXO3a mRNA expression and caspase-3 and BAX protein expression in ovarian tissue in the model group were increased (P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were decreased (P<0.01); compared with the model group, the mRNA expression of FOXO3a and protein expression of caspase-3 and BAX in ovarian tissue in the acupuncture group were decreased (P<0.05, P<0.01), and the mRNA expression of PI3K and AKT and the protein expression of p-PI3K, p-AKT, and p-FOXO3a in ovarian tissue were increased (P<0.01, P<0.05). CONCLUSION: Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could inhibit ovarian cell apoptosis, and improve ovarian function in POR mice, and its mechanism may be related to the regulation of key factors in the PI3K/AKT/FOXO3a pathway.

Fermented Aronia melanocarpa pomace improves the nutritive value of eggs, enhances ovarian function, and reshapes microbiota abundance in aged laying hens.

Introduction: There is a decline in the quality and nutritive value of eggs in aged laying hens. Fruit pomaces with high nutritional and functional values have gained interest in poultry production to improve the performance. Methods: The performance, egg nutritive value, lipid metabolism, ovarian health, and cecal microbiota abundance were evaluated in aged laying hens (320 laying hens, 345-day-old) fed on a basal diet (control), and a basal diet inclusion of 0.25%, 0.5%, or 1.0% fermented Aronia melanocarpa pomace (FAMP) for eight weeks. Results: The results show that 0.5% FAMP reduced the saturated fatty acids (such as C16:0) and improved the healthy lipid indices in egg yolks by decreasing the atherogenicity index, thrombogenic index, and hypocholesterolemia/hypercholesterolemia ratio and increasing health promotion index and desirable fatty acids (P < 0.05). Additionally, FAMP supplementation (0.25%-1.0%) increased (P < 0.05) the ovarian follicle-stimulating hormone, luteinizing hormone, and estrogen 2 levels, while 1.0% FAMP upregulated the HSD3B1 expression. The expression of VTG II and ApoVLDL II in the 0.25% and 0.5% FAMP groups, APOB in the 0.5% FAMP group, and ESR2 in the 1% FAMP group were upregulated (P < 0.05) in the liver. The ovarian total antioxidant capacity was increased (P < 0.05) by supplementation with 0.25%-1.0% FAMP. Dietary 0.5% and 1.0% FAMP downregulated (P < 0.05) the Keap1 expression, while 1.0% FAMP upregulated (P < 0.05) the Nrf2 expression in the ovary. Furthermore, 1.0% FAMP increased cecal acetate, butyrate, and valerate concentrations and Firmicutes while decreasing Proteobacteria (P < 0.05). Conclusion: Overall, FAMP improved the nutritive value of eggs in aged laying hens by improving the liver-blood-ovary function and cecal microbial and metabolite composition, which might help to enhance economic benefits.

Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse.

The female reproductive system is one of the first to age in humans, resulting in infertility and endocrine disruptions. The aging ovary assumes a fibro-inflammatory milieu which negatively impacts gamete quantity and quality as well as ovulation. Here we tested whether the systemic delivery of anti-inflammatory (Etanercept) or anti-fibrotic (Pirfenidone) drugs attenuates ovarian aging in mice. We first evaluated the ability of these drugs to decrease the expression of fibro-inflammatory genes in primary ovarian stromal cells. Whereas Etanercept did not block Tnf expression in ovarian stromal cells, Pirfenidone significantly reduced Col1a1 expression. We then tested Pirfenidone in vivo where the drug was delivered systemically via mini-osmotic pumps for 6-weeks. Pirfenidone mitigated the age-dependent increase in ovarian fibrosis without impacting overall health parameters. Ovarian function was improved in Pirfenidone-treated mice as evidenced by increased follicle and corpora lutea number, AMH levels, and improved estrous cyclicity. Transcriptomic analysis revealed that Pirfenidone treatment resulted in an upregulation of reproductive function-related genes at 8.5 months and a downregulation of inflammatory genes at 12 months of age. These findings demonstrate that reducing the fibroinflammatory ovarian microenvironment improves ovarian function, thereby supporting modulating the ovarian environment as a therapeutic avenue to extend reproductive longevity.

Ovarian function in female survivors of high-risk neuroblastoma.

INTRODUCTION: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy. METHODS: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI. RESULTS: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy. DISCUSSION: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy.

Revisiting ovarian function suppression with GnRH agonists for premenopausal women with breast cancer: Who should use and the impact on survival outcomes.

Breast cancer diagnosed in premenopausal women tends to be more aggressive and the benefit of ovarian function suppression (OFS), at least in certain groups of patients, is well known. There is hesitancy in using OFS in some groups of patients who may otherwise benefit from the treatment. For instance, it is clear that in premenopausal patients with hormone receptor-positive (HR+), high-risk, early-stage breast cancer, gonadotropin-releasing hormone agonists (GnRHa) should be given in the adjuvant setting; however, confusion remains whether premenopausal patients with intermediate-risk disease benefit from GnRHa, given the lack of consensus on its definition in guidelines and clinical practice. Most recent evidence on the long-term efficacy of GnRHa, with up to 20-years of follow-up, reinforced its benefits in premenopausal patients with early-stage breast cancer. In this comprehensive review, we reviewed the long-term efficacy in terms of improvement in disease-free survival (DFS) and overall survival (OS) for early-stage HR+ breast cancer and examined evidence from multiple randomized clinical studies to identify the clinicopathological characteristics that correlated with improved DFS and OS with the addition of OFS to adjuvant endocrine therapy. Other aspects of GnRHa, including its efficacy in advanced breast cancer, safety profile, evidence in ovarian function preservation, and the advantages of long-acting formulations were also discussed. By addressing the existing gaps and grey areas regarding the inclusion of OFS as a crucial treatment component for premenopausal breast cancer patients, physicians are more aware of who to administer and the potential impact on survival outcomes.

Impact of oxidative stress induced by heavy metals on ovarian function.

As a crucial organ of the female reproductive system, the ovary has both reproductive and endocrine functions. Oxidative stress refers to an increase in intracellular reactive oxygen species (ROS), which play a role in the normal physiological activity of the ovary. However, excessive ROS can cause damage to the ovary. With the advancement of human industrial activities, heavy metal pollution has become increasingly severe. Heavy metals cause oxidative stress through both direct and indirect mechanisms, leading to changes in signal transduction pathways that damage the ovaries. This review aims to outline the adverse effects of oxidative stress on the ovaries triggered by heavy metals such as copper, arsenic, cadmium, mercury, and lead. The detrimental effects of heavy metals on ovaries include follicular atresia and decreased estrogen production in experimental animals, and they also cause premature ovarian insufficiency in women. Additionally, this review discusses the role of antioxidants, provides some treatment methods, summarizes the limitations of current research, and offers perspectives for future research directions.

Downregulation of CASC15 attenuates the symptoms of polycystic ovary syndrome by affecting granulosa cell proliferation and regulating ovarian follicular development.

Polycystic ovary syndrome (PCOS) is a type of follicular dysplasia with an unclear pathogenesis, posing certain challenges in its diagnosis and treatment. Cancer susceptibility candidate 15 (CASC15), a long non-coding RNA closely associated with tumour development, has been implicated in PCOS onset and development. Therefore, this study aimed to investigate the molecular mechanisms underlying PCOS by downregulating CASC15 expression in both in vitro and in vivo models. We explored the potential regulatory relationship between CASC15 expression and PCOS by examining cell proliferation, cell cycle dynamics, cell autophagy, steroid hormone secretion capacity, and overall ovarian function in mice. We found that CASC15 expression in granulosa cells derived from patients with PCOS was significantly higher than those of the normal group (P < 0.001). In vitro experiments revealed that downregulating CASC15 significantly inhibited cell proliferation, promoted apoptosis, induced G1-phase cell cycle arrest, and influenced cellular autophagy levels. Moreover, downregulating CASC15 affected the follicular development process in newborn mouse ovaries. In vivo studies in mice demonstrated that disrupting CASC15 expression improved PCOS-related symptoms such as polycystic changes and hyperandrogenism, and significantly affected ovulation induction and embryo implantation in pregnant mice. Overall, CASC15 was highly expressed in granulosa cells of patients with PCOS and its downregulation improved PCOS-related symptoms by influencing granulosa cell function and follicular development in mice.

Folliculogenesis and steroidogenesis alterations after chronic exposure to a human-relevant mixture of environmental toxicants spare the ovarian reserve in the rabbit model.

BACKGROUND: Industrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known target of endocrine-disrupting chemicals. This function holds biological processes that are decisive for the fertility of women themselves and for the health of future generations. However, insufficient research has evaluated the risk of combined mixtures on this function. This study aimed to assess the direct impacts of a realistic exposure to eight combined environmental toxicants on the critical process of folliculogenesis. METHODS: Female rabbits were exposed daily and orally to either a mixture of eight environmental toxicants (F group) or the solvent mixture (NE group, control) from 2 to 19 weeks of age. The doses were computed from previous toxicokinetic data to reproduce steady-state serum concentrations in rabbits in the range of those encountered in pregnant women. Ovarian function was evaluated through macroscopic and histological analysis of the ovaries, serum hormonal assays and analysis of the expression of steroidogenic enzymes. Cellular dynamics in the ovary were further investigated with Ki67 staining and TUNEL assays. RESULTS: F rabbits grew similarly as NE rabbits but exhibited higher total and high-density lipoprotein (HDL) cholesterol levels in adulthood. They also presented a significantly elevated serum testosterone concentrations, while estradiol, progesterone, AMH and DHEA levels remained unaffected. The measurement of gonadotropins, androstenedione, pregnenolone and estrone levels yielded values below the limit of quantification. Among the 7 steroidogenic enzymes tested, an isolated higher expression of Cyp19a1 was measured in F rabbits ovaries. Those ovaries presented a significantly greater density/number of antral and atretic follicles and larger antral follicles without any changes in cellular proliferation or DNA fragmentation. No difference was found regarding the count of other follicle stages notably the primordial stage, the corpora lutea or AMH serum levels. CONCLUSION: Folliculogenesis and steroidogenesis seem to be subtly altered by exposure to a human-like mixture of environmental toxicants. The antral follicle growth appears promoted by the mixture of chemicals both in their number and size, potentially explaining the increase in atretic antral follicles. Reassuringly, the ovarian reserve estimated through primordial follicles number/density and AMH is spared from any alteration. The consequences of these changes on fertility and progeny health have yet to be investigated.

Gynotoxic Effects of Chemotherapy and Potential Protective Mechanisms.

Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs.

Palbociclib combined with endocrine treatment in hormone receptor-positive, HER2-negative breast cancer patients with high relapse risk after neoadjuvant chemotherapy: subgroup analyses of premenopausal patients in PENELOPE-B.

BACKGROUND: The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC at high risk of relapse [defined as no pathological complete response after neoadjuvant chemotherapy and a clinical, pathological stage, estrogen receptor, grading (CPS-EG) score ≥3 or 2/ypN+] were randomized to receive 13 cycles of palbociclib or placebo + standard ET. Ovarian function (OF) was evaluated by centrally assessed estradiol, follicle-stimulating hormone and anti-Müllerian hormone serum levels. RESULTS: Overall, 616 of 1250 randomized patients were premenopausal; of these, 30.0% were <40 years of age, 47.4% had four or more metastatic lymph nodes, and 58.2% had a CPS-EG score ≥3. 66.1% of patients were treated with tamoxifen alone, and 32.9% received ovarian function suppression (OFS) in addition to either tamoxifen or aromatase inhibitor (AI). After a median follow-up of 42.8 months (97.2% completeness) no difference in iDFS between palbociclib and placebo was observed [hazard ratio = 0.95, 95% confidence interval (CI) 0.69-1.30, P = 0.737]. The estimated 3-year iDFS rate was marginally higher in the palbociclib arm (80.6% versus 78.3%). Three year iDFS was higher in patients receiving AI than tamoxifen plus OFS or tamoxifen alone (86.0% versus 78.6% versus 78.0%). Patients receiving tamoxifen plus OFS showed a favorable iDFS with palbociclib (83.0% versus 74.1%, hazard ratio = 0.52, 95% CI 0.27-1.02, P = 0.057). Hematologic adverse events were more frequent with palbociclib (76.1% versus 1.9% grade 3-4, P < 0.001). Palbociclib seems not to negatively impact the OF throughout the treatment period. CONCLUSIONS: In premenopausal women, who received tamoxifen plus OFS as ET, the addition of palbociclib to ET results in a favorable iDFS. The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period.

Ovarian function recovery in breast cancer patients receiving adjuvant anastrozole treatment: updated results from the phase 3 DATA trial.

PURPOSE: Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results. METHODS: Postmenopausal women with HR+ BC who were 45-57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method. RESULTS: This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85-2.81), DRFS (HR = 1.51; 95% CI 0.73-3.11), OS (HR = 1.64; 95% CI 0.75-3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84-4.63) when compared with patients without OFR. CONCLUSION: In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.

Intraovarian platelet-rich plasma injection in poor responders.

OBJECTIVE: To evaluate if it possible to improve ovarian reserve parameters and oocyte retrieval in poor responders who undergo intraovarian injection of platelet-rich plasma (PRP). METHODS: Prospective cohort study. We included 148 poor responders who underwent PRP injection between October 2021 and December 2022 in our institution, comparing pre and post PRP ovarian function. In addition, the IVF outcomes of a subgroup of patients was studied after the intervention in contrast with the previous treatment. RESULTS: An improvement in ovarian reserve was observed in relation to previous values: FSH (13.57 vs. 11.32, p=0.11), AMH (0.39 vs. 0.48, p=0.06), antral follicle count (3.98 vs. 5.75, p<0.001); as well as a higher number of oocytes retrieved (2.63 vs. 3.65, p=0.01) and produced embryos (1.64 vs. 2.22, p=0.03); without a great impact on pregnancy rates. CONCLUSIONS: Although experimental, intraovarian PRP could restore ovarian function and be postulated as an alternative to oocyte donation in patients with low ovarian reserve who do not accept this treatment. There is a lack of randomized controlled trials to support these findings.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment: A prospective study.

BACKGROUND: Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques. AIM: To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). METHODS: This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment. RESULTS: The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment. CONCLUSION: UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Pu-erh tea theabrownin improves the ovarian function and gut microbiota in laying hens.

Studies have reported that theabrownin can moderate the lipid metabolism and intestinal microbiota, thereby affecting the health of humans and model animals, however the research on laying hens is scarce. The present study aimed to investigate the effects of dietary theabrownin supplementation on lipid metabolism, microbial composition and ovarian function in laying hens. A total of 80 laying hens (25 wk of age) were fed with normal diet (CON) and normal diet +100 mg/kg theabrownin (PT group) for 12 wk. The results showed that the addition of theabrownin enhanced villus height of duodenum and decreased crypt depth of jejunum (P < 0.05). At the same time, compared with CON, the concentration of IL-6 and the mRNA expression of IL-1ß and IL-6 were decreased significantly in PT group (P < 0.05). Dietary theabrownin reduced the concentration of total cholesterol and glycerol, while decreased lipid droplet optical density in liver (P < 0.05). Compared with CON group, the mRNA expression of PPARγ, HMG-CoAS, ACC were down-regulated and the mRNA expression of CYP8B1 was up-regulated in PT group (P < 0.05). The ACE, Chao1 and Observed_species indexes in cecum microbiota were increased by PT group intervention (P < 0.05). Dietary PT supplementation enhanced the relative abundance of Firmicutes (phylum), Lactobacillus (genus) and the Firmicutes to Bacteroidetes ratio, and reduced the relative abundance of Bacteroidetes (phylum) in cecum (P < 0.05). The organic acids and its derivatives were up-regulated by theabrownin intervention in serum metabolites (P < 0.05). Dietary theabrownin supplementation resulted in higher mRNA expression of Bcl-2 and SIRT1 in ovary and increased the concentration of estradiol in serum (P < 0.05). These discovering indicated that dietary theabrownin supplementation enhanced the intestinal function and influenced serum metabolism by improving intestinal morphology, microbiota community structure and reducing the concentration and expression of inflammatory cytokines in intestine. Dietary theabrownin reduced hepatic lipid deposition and it also decreased the cell apoptosis rate to improve ovarian function and egg weight which were associated with the SIRT1 pathway.

Polysaccharide from Hericium erinaceus improved laying performance of aged hens by promoting yolk precursor synthesis and follicle development via liver-blood-ovary axis.

Little information is available on the effect of Hericium erinaceus polysaccharides (HEP) on laying hens, especially on improving liver and ovarian health and function. Therefore, this study was conducted to investigate the impacts of HEP on liver and ovarian function to delay the decline in the laying performance of aged hens. A total of 360 fifty-eight-wk-old laying hens were randomly allocated to 4 treatments, with 6 replicates of 15 birds each. After 2 wk of adaptation, the birds were fed basal diet (CON) or basal diets supplemented with 250, 500, and 750 mg/kg of HEP (HEP250, HEP500, and HEP 750, respectively) for 12 wk. The results showed that, compared with CON, hens fed HEP had significantly increased laying performance (P < 0.05) and promoted follicle development, as evidenced by the increased numbers of hierarchical follicles, small follicles, and total follicles (P < 0.05). Birds fed 500 mg/kg of HEP improved the liver function by increasing T-AOC activity (P < 0.05) and decreasing hepatic oxidative stress and inflammatory responses (inflammatory cell infiltration) caused by aging. The lipid metabolism was improved, and yolk precursor synthesis was promoted in the liver of HEP-treated laying hens by upregulating the mRNA expression of FAS, MTTP, PPAR-α, APOVLDL-Ⅱ, and VTG-Ⅱ (P < 0.05). In addition, HEP significantly decreased ovarian inflammation by regulating the mRNA levels of NF-κB, IL-1ß, IL-6, and TNF-α (P < 0.05). As a result, the contents of E2, LH, and FSH in serum and the gene expression of ERα of the liver and FSHR of the ovary increased in HEP-treated hens (P < 0.05). In conclusion, dietary HEP supplementation exhibited potential hepatic and ovarian protective effects, thereby increasing the laying performance of aged hens by enhancing reproductive hormone secretion hormone secretion and promoting yolk precursor synthesis and follicle development via the liver-blood-ovary axis. The optimal supplementation level of HEP in aged hens was 500 mg/kg.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Consistent and effective method to define the mouse estrous cycle stage by a deep learning-based model.

The mouse estrous cycle is divided into four stages: proestrus (P), estrus (E), metestrus (M), and diestrus (D). The estrous cycle affects reproductive hormone levels in a wide variety of tissues. Therefore, to obtain reliable results from female mice, it is important to know the estrous cycle stage during sampling. The stage can be analyzed from a vaginal smear under a microscope. However, it is time-consuming, and the results vary between evaluators. Here, we present an accurate and reproducible method for staging the mouse estrous cycle in digital whole-slide images (WSIs) of vaginal smears. We developed a model using a deep convolutional neural network (CNN) in a cloud-based platform, Aiforia Create. The CNN was trained by supervised pixel-level multiclass semantic segmentation of image features from 171 hematoxylin-stained samples. The model was validated by comparing the results obtained by CNN with those of four independent researchers. The validation data included three separate studies comprising altogether 148 slides. The total agreement attested by the Fleiss kappa value between the validators and the CNN was excellent (0.75), and when D, E, and P were analyzed separately, the kappa values were 0.89, 0.79, and 0.74, respectively. The M stage is short and not well defined by the researchers. Thus, identification of the M stage by the CNN was challenging due to the lack of proper ground truth, and the kappa value was 0.26. We conclude that our model is reliable and effective for classifying the estrous cycle stages in female mice.