Oocyte Quality Research Articles

Inhibition of ferroptosis counteracts the advanced maternal age-induced oocyte deterioration.

Ferroptosis, a recently discovered form of programmed cell death triggered by the excessive accumulation of iron-dependent lipid peroxidation products, plays a critical role in the development of various diseases. However, whether it is involved in the age-related decline in oocyte quality remains unexplored. Here, we took advantage of nano-proteomics to uncover that reduced ferritin heavy chain (Fth1) level is a major cause leading to the occurrence of ferroptosis in aged oocytes. Specifically, induction of ferroptosis in young oocytes by its activators RSL3 and FAC, or knockdown of Fth1 all phenocopied the meiotic defects observed in aged oocytes, including failed oocyte meiotic maturation, aberrant cytoskeleton dynamics, as well as impaired mitochondrial function. Transcriptome analysis showed that knockdown of Fth1 affected meiosis-related and aging-related pathways in oocytes. Conversely, inhibition of ferroptosis by its inhibitors or expression of Fth1 improved the quality of aged oocytes. We also validated the effects of ferroptosis on the porcine oocyte quality in vitro. Altogether, we demonstrate the contribution of ferroptosis to the age-induced oocyte defects and evidence that inhibition of ferroptosis might be a feasible strategy to ameliorate the reproductive outcomes of female animals at an advanced age.

Anti-Müllerian Hormone Concentration Measured Before Gonadotropin Stimulation is Associated with Quality of Subsequent Ovarian Response in the Cheetah (Acinonyx jubatus) and Domestic Cat (Felis catus)

Abstract Relationships between anti-Müllerian hormone (AMH) concentrations and subsequent ovarian stimulation outcomes have been demonstrated in several mammalian species, but comprehensive reports are lacking in felids. The objective of this study was to characterize relationships between AMH concentrations and responses to exogenous gonadotropin stimulation in cheetahs and domestic cats. Blood samples collected before stimulation were used to measure serum AMH concentrations, which were compared to post-stimulation outcomes, including counts of retrievable oocytes or ovulation sites, oocyte quality, embryonic cleavage after in vitro fertilization, and progestogen concentrations. Comparisons were also made between AMH concentrations and outcomes in domestic cats induced to ovulate by mechanical stimulation of the vagina and cervix (simulated coitus). Greater AMH concentrations were associated with greater ovulatory response, progestogen production, and embryonic cleavage success among gonadotropin-treated cheetahs, and with greater ovulatory response among gonadotropin-treated domestic cats. Associations were moderated by age, with AMH concentration generally a greater determinant of these outcomes in older animals. Using only AMH concentrations, domestic cats with high and low ovulatory responses to exogenous hormones could be distinguished. However, this marker was unrelated to ovulatory response in domestic cats after simulated coitus. These results demonstrate the potential for AMH concentrations to predict responses of cheetahs and domestic cats to ovarian stimulation treatment commonly used in assisted reproductive technologies. Associations between AMH concentrations and ovarian stimulation outcomes in these species might derive from relationships between AMH concentration and antral follicle count or oocyte/embryo cellular function, as reported in other mammals; however, this remains to be tested.

Elective Oocyte Cryopreservation

Introduction: In recent years, techniques for oocyte cryopreservation have aided in preserving women's fertility. Initially, oocyte cryopreservation was implemented for females with diminished ovarian reserves. This approach is appropriate for women who are at risk of diminished ovarian reserves, including those undergoing chemotherapy, radiotherapy, or other conditions impacting ovarian reserve. It provides them the opportunity to have biological children later on. As more women choose to delay pregnancy and face declining ovarian reserves with age, oocyte cryopreservation has been made available to healthy women. Research did not demonstrate any difference in fertilization and pregnancy rates between fresh and frozen-thawed oocytes. Assessing ovarian reserve is essential prior to this procedure. Anti-Müllerian hormone levels and antral follicle counts are regarded as the most accurate indicators for forecasting ovarian response. Age is recognized as the key factor influencing oocyte quality and success rate. There is no agreement on the optimal age and quantity of oocytes for oocyte cryopreservation. Certain researchers have suggested an age limit of less than 35 years. Each additional frozen oocyte holds significance. Having 25 oocytes is linked to a 95% cumulative live birth rate in women under 35 years old. Conclusion: Elective oocyte cryopreservation provides an opportunity for women to preserve their fertility in future. Cryopreserved oocyte can lead to decreased risk of oocyte donation in the future and allows women to have their own genetic child. It is important that providers ensure that these women are informed about efficacy, safety and help them to make the best decisions. Some researchers have recommended an age below 35 years.

The Role of Platelet-Rich Plasma (PRP) in Enhancing IVF Success in Women With Ovarian Insufficiency: A Cohort Study

- Ovarian insufficiency is a significant cause of infertility in women, with limited effective treatment options. Platelet-Rich Plasma (PRP), rich in concentrated growth factors, has shown regenerative potential in various medical fields. However, its efficacy as an adjunct in infertility treatment, particularly in women with ovarian insufficiency, remains unclear. This study investigates whether PRP administration improves the success of IVF cycles in this specific population. This cohort study followed women with ovarian insufficiency undergoing IVF at a fertility center. Participants were divided into two groups: the intervention group, which received PRP alongside the standard IVF protocol, and the control group, which received only the standard protocol. Data collected included patient demographics, hormonal levels, number and quality of retrieved oocytes, fertilization rates, embryo quality, and pregnancy outcomes. The primary outcome was IVF success, defined by clinical pregnancy rates. Secondary outcomes included hormonal changes, oocyte quality, and embryo development. Statistical analysis utilized descriptive statistics, chi-square tests, and t-tests to compare outcomes between groups. PRP administration led to significant reductions in FSH levels (P<0.001) and marked increases in AMH levels and antral follicle count (AFC) (P=0.001 and P<0.001, respectively). The number of oocytes, mature MII oocytes, and Grade A embryos also improved significantly (P ranging from 0.004 to 0.017). Although the increase in Grade B embryos was not statistically significant, it was higher post-PRP. Chemical pregnancies occurred in 25% of participants, with 20.83% resulting in clinical pregnancies, including 2.1% spontaneous pregnancies. PRP significantly enhanced ovarian reserve markers (FSH, AMH, AFC), oocyte quality, and embryo development, translating into improved fertility outcomes. The findings suggest that with longer follow-up and larger sample sizes, PRP could be validated as a promising adjunctive therapy for women with ovarian insufficiency undergoing IVF. These results align with prior research and highlight PRP’s potential to advance reproductive outcomes in this challenging patient population.

The effect of endometriosis on oocyte quality: mechanisms, diagnosis and treatment.

Endometriosis significantly impacts the physical and mental health of women of reproductive age. While some patients can achieve pregnancy through surgery or in vitro fertilization (IVF), many still struggle with IVF failure due to poor oocyte quality. This presents a major clinical challenge that requires immediate attention. The causes of oocyte quality decline in endometriosis patients are diverse and have not yet been definitively identified. Furthermore, effective diagnostic mechanisms and therapeutic strategies remain elusive. To provide possible clinical solutions to improve pregnancy rates in patients with endometriosis, this review evaluates the current literature on the impact of endometriosis on oocyte quality, the possible mechanisms and management strategies of endometriosis leading to poor oocyte quality.

Triptolide exposure triggers ovarian inflammation by activating cGAS-STING pathway and decrease oocyte quality in mouse.

Triptolide (TPL), a prominent bioactive constituent derived from the Chinese herb Tripterygium wilfordii, exhibits diverse pharmacological effects such as anti-tumor and anti-immune properties. Despite its extensive clinical application for the treatment of arthritis and immune disorders, TPL has been associated with multiorgan toxicity, including adverse effects on the female reproductive system. However, the precise mechanisms underlying TPL-induced ovarian damage remain poorly understood. In this study, employing a mouse toxicological model, exposure to TPL was observed to result in decreased ovarian coefficient and fertility. Subsequent research demonstrated TPL exposure affected mitochondrial function, increased mitochondrial outer membrane permeability, resulted in mtDNA releasing into the cytoplasm. These events subsequently activated cGAS-STING pathway, leading to ovarian inflammation. Furthermore, TPL exposure has been found to disrupt the meiotic maturation of oocytes, which is mechanistically associated with suboptimal morphology of spindle and microtubule organizing centers (MTOCs). This association has been further confirmed through the use of reduced representation bisulfite sequencing (RRBS). In conclusion, our study demonstrates that TPL exposure can hinder follicular development, resulting in ovarian inflammation and reduced oocyte quality.

Genetic loss of Uchl1 leads to female infertility by affecting oocyte quality and follicular development.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme specifically highly expressed in the brain and gonads. Inhibition of UCHL1 hydrolase activity impairs oocyte maturation. Uchl1 knockout mice exhibit reproductive dysfunction, but the underlying pathogenesis remains unclear. Uchl1 knockout mice were used to explore the role of UCHL1 in oocyte maturation and follicle development. Oocyte development potential and mitochondrial membrane potential were also assessed to determine UCHL1 function on early embryo development. Transcriptome and proteomic analyses were conducted to elucidate molecular changes associated with Uchl1 knockout. Uchl1-/- mice exhibited ovarian dysfunction and infertility, with decreased serum estrogen, reduced antral follicle number, and diminished oocyte developmental potential compared to wild types. Histological examination revealed compromised follicle development and disrupted granulosa cell function in Uchl1-/- ovaries. In vitro, Uchl1-/- follicles had impaired preantral follicle development and poor FSH response. Loss of UCHL1 not only leads to mitochondrial dysfunction in oocytes, but also negatively affected estrogen biosynthesis with downregulation of steroidogenic acute regulatory protein (STAR) and estrogen receptor alpha (ER-α) in granulosa cells. Additionally, downregulated expression of connexin 37 (CX37), which is known to impair gap junction intercellular communication between oocyte and granulosa cells, transmitted the Uchl1 gene damage from oocyte to granulosa cells, which in turn affected functions of follicles and even the whole ovary. Loss of UCHL1 leads to significant disruptions in follicular development and oocyte quality, resulting in infertility. UCHL1 in oocytes influences not only the quality and quantity of the oocytes themselves, but also the follicles and the ovaries as a whole. This disruption ultimately manifests in symptoms similar to diminished ovarian reserve (DOR).

Curcumin Suppresses ROS Production and Increases Mitochondrial Activity in Cumulus Cells and Oocytes of COCs Derived From Non-Vascularized Follicles in Pigs.

In vitro maturation (IVM) produces offspring from domestic animals; however, the blastocyst rate after IVM was low. We previously reported that the developmental competence of oocytes derived from follicles with blood vessels absent on the surface (non-vascularized follicles: NVF) is quite low compared to those derived from follicles with blood vessels present on the surface (vascularized follicles: VF). Thus, it is important to develop technique to improve the quality of NVF-derived oocyte by IVM. Since it has been reported that reactive oxygen species (ROS) reduces oocyte quality, in this study, we investigated whether curcumin that is known as antioxidant could improve oocyte quality derived from NVF. As results, cultivation of NVF Cumulus-oocyte complexes (COCs) with curcumin significantly improved cumulus expansion and oocyte meiotic maturation of NVF COCs compared to those of NVF COCs without curcumin. Cultivation with curcumin of NVF COCs significantly improved the proliferative activity of cumulus cells. Furthermore, the cultivation significantly reduced ROS activity and increased mitochondrial activity. Hence, it was revealed that the addition of curcumin to the maturation medium increased mitochondrial activity and reduced ROS levels in NVF-derived cumulus cells and oocytes, thereby improving the maturation of oocytes within COCs.

Oocyte transcriptomes and follicular fluid proteomics of ovine atretic follicles reveal the underlying mechanisms of oocyte degeneration

BackgroundIn mammals, female fertility is influenced by the result of follicular development (ovulation or atresia). Follicular atresia is a complex physiological process that results in the degeneration of oocytes from the ovary. However, the molecular mechanisms of oocyte degeneration and key protein markers of follicular atresia remain unclear. In this study, we investigated the complex transcriptional regulatory mechanisms and protein profiles in oocytes and follicular fluid in atretic follicle stages using single-cell RNA sequencing and tandem mass tag proteomics.ResultsFirst, through paired analysis of different follicle development stages, we identified 175 atresia-specific genes and eight candidate oocyte-secreted factors, including PKG1, YTHDF2, and MYC. Meanwhile, we also characterized unique features of the oocyte transcriptional landscape in the atretic follicle stage that displayed cell death-related transcriptional changes and mechanisms, such as autophagy (TBK1 and IRS4), necroptosis (PKR), and apoptosis (MARCKS). Moreover, we identified atresia-specific genes, namely FTH1, TF, and ACSL4, which may participate in regulation of oocyte ferroptosis in atretic follicles through a series of mechanisms including ferritinophagy, ferritin transport, and lipid metabolism. Additionally, we uncovered 333 differentially expressed proteins that may coordinate follicular atresia and revealed key pathways, such as negative regulation of angiogenesis, metabolic pathways, and transcription and mRNA splicing, that lead to oocyte degeneration. Finally, by combining transcriptome and proteomics analyses, we identified two oocyte-secreted biomarkers, PGK1 and ANGPT2, that may be associated with follicular atresia.ConclusionsIn conclusion, our work offers a thorough characterization of oocyte transcription mechanism and follicular fluid protein changes in ovine atretic follicles, which offers a crucial reference for analyzing the mechanism of follicular atresia and establishing an oocyte quality assessment system in sheep.

Atractylenolide Ⅲ partially alleviates tunicamycin-induced damage in porcine oocytes during in vitro maturation by reducing oxidative stress.

Assisted reproductive technology (ART) is widely used to address infertility and enhance reproductive outcomes in livestock. Among various ART techniques, in vitro maturation (IVM) is commonly used to obtain high-quality oocytes but is susceptible to oxidative stress. In traditional Chinese medicine, Rhizoma Atractylodis Macrocephalae (Bai Zhu) is used to enhance maternal and fetal health. Atractylenolide Ⅲ (AⅢ), a major component of Bai Zhu, has shown both antioxidant properties and oxidative stress induction, leading to controversy. This study used porcine oocytes as a model to investigate the effects of AⅢ under tunicamycin (TM)-induced oxidative stress. During IVM, oocytes were treated with various concentrations of AⅢ and a constant dose of TM. AⅢ promoted oocyte maturation and cumulus cell expansion, with the optimal concentration being 1 mg/L. AⅢ reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating reduced oxidative damage. Mitochondrial function and membrane potential (MMP) were preserved in AⅢ-treated oocytes. Additionally, AIII could alleviate TM-induced endoplasmic reticulum (ER) stress, as shown by decreased mRNA expression of ER stress markers. Following parthenogenetic activation (PA), AⅢ-treated oocytes exhibited increased cleavage and blastocyst formation rates with reduced apoptosis compared to the TM group. These findings suggest that AⅢ protects against oxidative stress, improving oocyte quality and developmental potential, with potential applications in ART.

Ovarian premature aging: VIP as key regulator of fibro-inflammation and foamy macrophages generation.

Ovarian aging is associated with fibro-inflammation, contributing to the decline in oocyte count and quality. Given the immunomodulatory properties of the vasoactive intestinal peptide (VIP) in the reproductive tract, we investigated its role in maintaining ovarian immune homeostasis and preventing premature aging. We evaluated young VIP knockout (KO) mice, comparing them to young wild type (WT) females, for signs of premature aging. Histological staining revealed aberrant ovarian morphology in VIP KO mice, characterized by increased atretic follicles and decreased ovarian reserve compared to WT controls. Moreover, VIP KO ovaries showed reduced vascularization, increased collagen deposition and elevated ROS and IL-1β levels. Foamy macrophages were significantly predominant, indicating premature aging in young VIP KO ovaries. To determine potential mechanisms behind these pathogenic changes, we conditioned peritoneal macrophages from young WT or VIP KO mice in vitro with ovarian-conditioned media from young WT or VIP KO mice to mimic the respective ovarian microenvironment. When WT or VIP KO peritoneal macrophages were conditioned with ovarian media from their respective genotypes, lipid droplet accumulation increased compared to control medium. In cross-genotype experiments, WT macrophages conditioned with media from VIP KO ovaries selectively accumulated higher levels of lipid droplets, whereas no differences were observed in VIP KO macrophages conditioned with WT ovarian media. This suggests that VIP KO macrophages are uniquely sensitized to the inflammatory environment of VIP KO ovaries, implicating both ovarian factors and macrophage status. These findings highlight the role of VIP in preventing fibro-inflammation, thereby preserving ovarian health and preventing premature aging.

Chlorogenic Acid Ameliorates Chronic Unpredictable Stress-Induced Diminished Ovarian Reserve Through Ovarian Renin-Angiotensin System.

Chronic stress could impair ovarian reserve through hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to reduced oocyte quality and endocrine dysfunction. The ovarian renin-angiotensin system (OVRAS) modulates follicular development, and excessive activation of the ACE-AngII-AT1R axis increases oxidative stress, disrupting ovarian function. This study investigates OVRAS's role in chronic unpredictable stress (CUS)-induced diminished ovarian reserve (DOR) and explores the protective effects of chlorogenic acid (CGA). Female mice were subjected to CUS (10 intervention methods were randomly applied to mice according to low, medium, and high frequency) and CGA treatment. Hormone levels, estrous cycles, ovarian morphology, oxidative stress, and apoptosis were evaluated. Results demonstrated that CUS overactivated the ACE-AngII-AT1R axis, increasing oxidative stress and apoptosis in granulosa cells (GCs). CGA improved ovarian function, reduced oxidative stress, and downregulated ACE-AngII-AT1R axis activity. CGA may alleviate stress-induced DOR by mitigating oxidative stress and apoptosis via modulation of the ACE-AngII-AT1R axis.

Optimal aspiration pressure of suction pump for oocyte retrieval in infertile patients undergoing in vitro fertilization.

The oocyte retrieval is a critical step in assisted reproductive technologies, including in vitro fertilization and fertility preservation. Despite evolving techniques, the optimal aspiration pressure during retrieval remains debatable, with limited in vivo human studies. Existing studies, primarily in vitro and on animals, suggest that inappropriate aspiration pressures can impair oocyte quality. This study aims to compares the effects of two different aspiration pressures, 120mmHg and 150mmHg, on oocyte recovery, damage, and subsequent embryo development and pregnancy outcomes in infertile women undergoing transvaginal ultrasound-guided oocyte retrieval. This retrospective study analyzed data from 891 women at Seoul National University Hospital between May 2018 and August 2023. A total of 400 cycles were included, with 202 at 120 mmHg and 198 at 150 mmHg aspiration pressures. The primary outcomes were the number of retrieved, matured, fractured oocytes, embryos, and good-grade embryos. Pregnancy outcomes were evaluated by comparing the clinical pregnancy rates and live birth rates. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship between aspiration pressure, clinical pregnancy, and live birth rates. There was statistically significant difference in the number of retrieved oocytes and mature oocytes between the 120 mmHg group and the 150 mmHg group (6.3±5.2 vs. 7.7±6.7, p = 0.018; 4.4±3.7 vs. 5.6±5.3, p = 0.011). The number of embryos and good grade embryos also differed significantly (3.3±3.1 vs. 4.2±3.9, p = 0.011; 1.0±1.6 vs. 1.5±2.6, p = 0.031). However, there were no significant differences in clinical pregnancy and live birth rates between the two groups in multivariate logistic regression analysis (adjusted OR = 0.725, p = 0.519; adjusted OR = 0.370, p = 0.170). Increasing the aspiration pressure to 150mmHg led to a higher yield of oocytes and embryos than 120mmHg, without any negative impact on oocyte quality or live birth rates. These findings provide valuable insights for clinical decision-making in infertility treatments, suggesting that 150mmHg may be a more effective pressure for oocyte retrieval in in vitro fertilization and embryo transfer.

Effects of 100 IU versus 150 IU hCG supplementation on oocyte and embryo quality in patients aged ≥ 35 years: a propensity score-matched analysis

Effects of 100 IU versus 150 IU hCG supplementation on oocyte and embryo quality in patients aged ≥ 35 years: a propensity score-matched analysis

Reproductive outcomes in infertile women with endometriosis undergoing ART.

Background Endometriosis-related infertility and its treatment with assisted reproductive technologies (ART) have been broadly researched. Yet, underlying mechanisms of infertility, particularly in the absence of tubal dysfunction, remain unclear. While the impact of inflammatory milieu on the ovary and/or endometrium has been indicated as a contributing factor, recent evidence from euploid transfers and donor cycles questions the extent of these effects. Moreover, the frequent coexistence of other confounders, such as adenomyosis, further complicates the clinical picture, making it difficult to isolate the specific impact of endometriosis on ART outcomes. Objectives To evaluate the influence of endometriosis on various aspects of ART, including oocyte competence, ART success and whether surgical or medical treatments improve these. Methods We primarily focused on recent high-quality sources, including systematic reviews, large-scale observational studies, and meta-analyses, to ensure a robust and reliable synthesis of the available evidence. Outcome While oocyte yield can decrease in the presence of an endometrioma or history of endometrioma excision, oocyte quality, early embryo development indicators, aneuploidy rates, and clinical outcomes of endometriosis patients do not differ from other infertility diagnoses in ART settings. Surgical treatments and hormonal suppression before ART do not seem to improve outcomes. Ovarian stimulation for ART does not seem to exacerbate endometriosis. Conclusions and Outlook Endometriosis, despite its high prevalence among infertile patients, does not inherently impair ART success, except in cases where ovarian reserve is compromised due to ovarian disease or its surgical treatment. The causal link between endometriosis and infertility remains an enigma, and future studies should continue to explore this association with other confounding factors.

Monocyte and Macrophage in Follicular Liquid: Predictive Markers of Embryo Quality in Women with Obesity and Infertility.

Over the past five years, the pregnancy rate in assisted reproductive technology (ART) programs in Russia has remained relatively stable. The aim of this study was to assess the distribution of monocyte and macrophage subsets in the blood and follicular fluid of infertile women undergoing assisted reproductive technology. The study involved 45 women with a mean age of 35 ± 4.66 years. Monocytes and macrophages were identified using flow cytometry. We observed a decrease in the CD68+CD163+CD206+ and the CD68+CD163-CD206+ cells in patients with a body mass index (BMI) >25 by 0.19 times and 6.56 times, respectively, compared to the group with a BMI <25 (p = 0.031). Patients with fair oocyte quality had 3.6 times more oocytes than those with poor quality (p = 0.010). The relative content of CD14+163-206+ monocytes was found to be 24.15 times higher in the follicular fluid of women with poor embryo quality compared to the group with good embryos (p = 0.010). We also noted that the number of oocytes increased in women with male factor infertility (p = 0.020) and those with unspecified infertility when compared to tubal infertility. An increase in the relative content of CD14+163+206+ in the blood was higher in women with other causes of female infertility compared to those with male factor infertility (p = 0.010). The relative content of M2-monocytes (CD14+163+206-) in the blood was 4.38 times higher in women with male factor infertility than in women with unexplained infertility (p = 0.010). A critical component of the inflammatory reaction in patients undergoing in vitro fertilization (IVF) involves more than just the activation of pro-inflammatory cells in response to ovarian stimulation. Our research shows that changes in the distribution of monocytes and macrophages can influence embryo implantation success and pregnancy outcomes in women. These processes are influenced by various infertility-related factors, including those mentioned above. However, these findings are preliminary and require further investigation.

Ceria Nanoparticles Improve the Quality of Aging Oocytes in Mice by Enhancing ROS Scavenging Ability

Ceria Nanoparticles Improve the Quality of Aging Oocytes in Mice by Enhancing ROS Scavenging Ability

Nicotinamide riboside supplementation ameliorates ovarian dysfunction in a PCOS mouse model

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility among women of reproductive age, yet the range of effective treatment options remains limited. Our previous study revealed that reduced levels of nicotinamide adenine dinucleotide (NAD+) in ovarian granulosa cells (GCs) of women with PCOS resulted in the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction. However, it is still uncertain whether increasing NAD+ levels in the ovaries could improve ovarian function in PCOS. In this study, we demonstrated that supplementation with the NAD+ precursor nicotinamide riboside (NR) prevented the decrease in ovarian NAD+ levels, normalized estrous cycle irregularities, and enhanced ovulation potential in dehydroepiandrosterone (DHEA)-induced PCOS mice. Moreover, NR supplementation alleviated ovarian fibrosis and enhanced mitochondrial function in ovarian stromal cells of PCOS mice. Furthermore, NR supplementation improved oocyte quality in PCOS mice, as evidenced by reduced abnormal mitochondrial clustering, enhanced mitochondrial membrane potential, decreased ROS levels, reduced spindle abnormality rates, and increased early embryonic development potential in fertilized oocytes. These findings suggest that supplementing with NAD+ precursors could be a promising therapeutic strategy for addressing ovarian infertility associated with PCOS.Graphical Ovarian NAD+ levels decreased in DHEA-induced PCOS mice, accompanied by mitochondrial dysfunction in oocytes and ovarian stromal cells, resulting in reduced oocyte quantity and quality, decreased early embryonic development potential, and increased ovarian fibrosis. After increasing ovarian NAD+ levels by NR supplementation to restore PCOS-related impairment of mitochondria function, ovarian dysfunction in PCOS was attenuated as characterized by improved oocyte quantity and quality, enhanced early embryonic development potential, and decreased ovarian fibrosis.

MTOR signaling mediates energy metabolic equilibrium in bovine and mouse oocytes during the ovulatory phase†.

The mammalian target of rapamycin (mTOR) signaling pathway is activated by luteinizing hormone in preovulatory follicle. However, its impact on ovulation remains inadequately explored. Utilizing in vivo studies and in vitro fertilization, we demonstrated that the negative effect of inhibition of mTOR signaling by rapamycin on oocyte quality during the ovulatory phase, with a notable decrease in the total cell count of blastocysts, a reduction in gastrula size, and fetal degeneration on the 16th day of gestation while not affecting ovulated oocyte count or granulosa cell luteinization. Mechanistically, our study elucidated that in the ovulatory phase, mTOR signaling inhibition enhances lipid consumption, mitochondrial membrane potential of oocytes, and ATP generation. As a result, embryos derived from these oocytes exhibit higher levels of reactive oxygen species, insufficient energy supply, and lower developmental potency. Furthermore, the impact of mTOR signaling on oocytes remains consistent across various species, and its inhibition has been demonstrated to enhance energy metabolism during the in vitro maturation process of bovine oocytes. These findings demonstrate the critical role of mTOR signaling during the ovulatory phase in balancing oocyte energy metabolism, enriching our understanding of the role of mTOR on ovulation regulation.

Ustiloxin A impairs oocyte quality by disrupting organelles function.

Oocyte quality is pivotal for fertilization and early embryonic development. Ustiloxin A (UA), is an emerging mycotoxin that has been frequently detected in rice and paddy. Because UA has been reported to be phytotoxic and cytotoxic, it poses a potential hazard to human and animal health. However, the effects of UA on oocyte maturation remain unknown. Here, we investigated the effects of acute UA exposure on mouse oocyte maturation. First, UA exposure inhibited oocyte maturation in a concentration-dependent manner and induced meiotic arrest by disrupting spindle assembly and reducing actin density. Moreover, mitochondrial function was substantially disrupted in oocytes upon UA exposure. Aberrant mitochondrial distribution, substantial downregulation of mitochondrial dynamics-associated genes Mfn1, Mfn2 and Fis1, decreased membrane potential and TOM20 expression were observed in UA-exposed oocytes; these effects further led to oxidative stress and DNA damage. Furthermore, UA induced ER and Golgi dysfunction and triggered ER stress by increasing GRP78 expression, which ultimately resulted in autophagy and early apoptosis in oocytes. Therefore, these results demonstrate that UA impairs oocyte quality by disrupting organelles function, providing new insight into the influence of UA on female reproduction in mammals.