Search Results (55)

Background/Objectives: Osteoarthritis has been increasingly described as associated with systemic inflammation, raising the question of how it would affect fertility in young women with or without reproductive hormone administration. We studied oogenesis in mice with collagenase-induced osteoarthritis (CIOA) as a model system with fewer ethical limitations after estradiol (E2) or follicle-stimulating hormone (FSH) treatment. Methods: Oocytes have been isolated from mice subjected to various treatment regimens. The meiotic spindle, the chromatin, and the actin cap were fluorescently labeled and analyzed. Results: In addition to reduced maturation rates, specific oocyte abnormalities were registered when CIOA, FSH, or E2 were applied in isolation. Combined treatments showed that the spindle, chromatin, and actin cytoskeleton parameters were differently affected in oocytes from groups with CIOA treated by estradiol and those treated with FSH. Enlarged spindles, ooplasmic tubulin asters, aligned metaphases, and predominantly normal actin caps, often with an actin halo, were typical for groups with CIOA combined with estradiol. The groups with CIOA and FSH had slightly enlarged spindles, unaligned metaphases with degenerated chromatin surrounded by a cloud of depolymerized tubulin, and small actin caps. Conclusions: Our results show that experimental osteoarthritis with or without exogenous reproductive hormones negatively affects oogenesis, presumably due to systemic inflammatory factors making the ovarian microenvironment less capable of supporting oocyte maturation. Estradiol supplementation does not benefit oogenesis. FSH treatment induced cytoskeletal and chromatin abnormalities that presumably disturb the fertilization and development potential of affected oocytes. These data can have implications for assisted reproduction in cases of patients with osteoarthritis. Full article

Female reproductive aging is associated with a progressive decline in oocyte competence and reduced success in assisted reproductive technologies. While chromosomal abnormalities, mitochondrial dysfunction, and DNA damage have been extensively studied, these mechanisms do not fully explain developmental arrest in chromosomally euploid embryos or the variability in embryo competence. Human oocytes enter a transcriptionally quiescent state during meiotic maturation and rely almost entirely on the regulated translation of stored maternal messenger RNAs to support fertilization and early embryonic development until zygotic genome activation. In this context, translational fidelity becomes a critical determinant of proteome integrity and cellular function. Age-related alterations affecting ribosomal RNA integrity, transfer RNA modification, aminoacylation accuracy, and translational regulatory networks may impair the precision, timing, and coordination of protein synthesis. These defects can disrupt essential processes such as spindle assembly, cytoskeletal organization, and early cleavage dynamics, ultimately compromising embryo viability despite chromosomal normality. In addition, the follicular microenvironment, including redox balance, metabolic support, and signaling pathways, plays a crucial upstream role in maintaining translational integrity. This review integrates mechanistic evidence from molecular, cellular, and developmental studies to propose that progressive decline in translational fidelity represents a fundamental and previously underrecognized driver of reproductive aging. Understanding translational control as a central regulator of oocyte competence may provide new insights into unexplained IVF failure and support the development of novel biomarkers and therapeutic strategies aimed at preserving reproductive potential. Full article

Oxidative stress has emerged as a key factor regulating female fertility, reproductive aging, and the development of various gynecologic and pregnancy-associated diseases. While physiological concentrations of reactive oxygen species play a fundamental role in many aspects of normal reproduction such as folliculogenesis, oocyte maturation, implantation, and placental development, abnormal or chronic oxidative stress impairs redox homeostasis and promotes mitochondrial dysfunction, inflammation, DNA damage, and cellular senescence. Recent research interest has shifted toward next-generation dietary antioxidants, including bioactive polyphenols, carotenoids, micronutrients, and nutraceutical combinations with improved bioavailability and molecular targets. These compounds go beyond classical free-radical scavenging activity and modulate a network of redox-sensitive signaling pathways involved in autophagy, apoptosis, endocrine regulation, and immunological balance. In this review, we integrate current mechanistic advances into a cohesive framework that illustrates the regulation of key cellular processes affecting female reproductive physiology by next-generation dietary antioxidants. We also critically evaluate experimental, translational, and clinical data supporting their role in promoting reproductive outcomes, including oocyte quality, ovarian reserve, pregnancy success, and mitigation of age-related reproductive decline. We highlight their potential in the therapeutic intervention of oxidative stress-related conditions such as infertility, polycystic ovary syndrome, endometriosis, early ovarian insufficiency, and menopause-associated disorders. Finally, we discuss the current challenges associated with dosage optimization, bioavailability, long-term safety, and interindividual variability. We conclude by highlighting next-generation dietary antioxidants as a promising, widely available, and non-invasive approach to improve women’s reproductive health and promote fertility throughout their lifespan. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disorder that is increasingly recognized as a systemic condition with profound implications for female reproductive potential. In addition to pelvic distortion and impaired folliculogenesis, growing evidence indicates that intrinsic alterations in oocyte morphology, mitochondrial function, and developmental competence contribute to infertility. The disease is driven by a multifactorial interplay of somatic mutations, epigenetic remodeling, immune dysregulation, and aberrant steroid signaling, which together create a pro-inflammatory, oxidative, and fibrotic microenvironment. Elevated cytokines, reactive oxygen species, and disrupted granulosa-cell function within the follicular niche impair meiotic progression, cytoplasmic maturation, and mitochondrial integrity, potentially accelerating oocyte aging and diminishing reproductive longevity. Epigenetic and post-transcriptional disturbances—including altered DNA methylation, histone modifications, and RNA-splicing defects—further reinforce estrogen dominance, progesterone resistance, and impaired decidualization, with downstream consequences for ovarian–endometrial communication. Although morphological abnormalities have been documented in oocytes from women with endometriosis, clinical outcomes remain heterogeneous, highlighting the need for integrative models that connect molecular alterations to functional reproductive endpoints. A deeper understanding of these mechanisms is essential for identifying biomarkers of oocyte competence and modifiable strategies—ranging from nutritional optimization to reduction of environmental risk factors—in clinical care to safeguard the reproductive potential of women with endometriosis. Full article

Glyphosate (GLY), the active ingredient in widely used herbicides, was long considered specific to plants and bacteria, yet mounting evidence shows it can impair endocrine and reproductive functions in animals. Given its widespread use and environmental persistence, assessing its effects at regulatory-approved doses is critical. Here, adult female zebrafish (Danio rerio) were exposed for 21 days to different concentrations of dietary GLY at 0.5 mg/kg body weight/day (GLY0.5, acceptable daily intake, ADI), 5 mg/kg/day (GLY5), and 50 mg/kg/day (GLY50, no-observed-adverse-effect level, NOAEL). Our findings show that dietary GLY induces dose-dependent perturbations along the hepato-gonadal axis. At the highest dose, chronic stress responses were evident through elevated cortisol and cortisone, accompanied by hepatic glycogen accumulation and ferroptotic stress. Although follicle histology appeared normal, alterations in several genes involved in oocyte maturation and estrogen receptor signaling translated into reduced fertilization, revealing compromised gamete quality rather than overt follicular development abnormality. Likewise, the lowest dose triggered modifications in genes crucial for oogenesis without altering the follicle development, although in this case, potential compensatory mechanisms could have led to enhanced fertilization. GLY5 did not alter the number of fertilized eggs but significantly increased embryo mortality. Overall, dietary GLY disrupted hepatic metabolism, endocrine signaling, and reproduction in a non-monotonic manner, even at levels considered safe by EFSA. These findings highlight the need to reevaluate current safety thresholds with attention to female-specific reproductive risks. Full article

Oocyte-granulosa cell complexes (OGCs) cultivation is crucial for advancing reproductive biotechnology but remains incomplete and needs further optimization. Insulin-like growth factor-I (IGF-I) regulates granulosa cell proliferation and apoptosis, and numerous studies have confirmed its role in promoting ovarian follicle development. Porcine follicular fluid (PFF) contains factors beneficial for oocyte growth, which may enhance oocyte development. To investigate whether IGF-I and PFF improve the in vitro culture efficiency of porcine OGCs, we cultured OGCs with IGF-I (0, 10, 50, 100 ng/mL) and PFF (from 3 to 6 mm follicles) at concentrations of 0, 2.5%, 5%, 10%, respectively. The results revealed that 50 and 100 ng/mL IGF-I significantly increased the antrum formation rate of OGCs (from 61.11 ± 7.35% to 88.89 ± 7.35%) and diameter growth of oocytes (from 108.77 ± 0.27 µm to 114.94 ± 0.58 and 113.29 ± 0.50 µm, respectively). However, only the 50 ng/mL group, but not the 100 ng/mL group, significantly improved the maturation rate (38.13 ± 3.77% vs. 25.00 ± 3.27%, p < 0.05) of oocytes. Additionally, 50 ng/mL IGF-I downregulated BAX (a pro-apoptotic gene) and upregulated BCL-2 (an anti-apoptotic factor) in granulosa cells, ultimately reducing apoptosis. In contrast, none of the PFF doses used in this study induced the formation of enclosed antrum-like structures in OGCs, nor did they significantly enhance their in vitro development. Our findings demonstrate that 50 ng/mL IGF-I effectively promotes the in vitro growth of porcine early antral follicle-derived OGCs by reducing apoptosis, whereas tested PFF concentrations had no beneficial effects and induced abnormal granulosa cell growth. How PFF modulates the adherent and spreading growth of granulosa cells has not been fully elucidated and requires further clarification. Full article

Background/Objectives: Approximately 50% of infertility cases are attributable to male factors; yet conventional semen examination can not identify the molecular abnormalities that hinder sperm functionality. Extracellular vesicles (EVs) derived from sperm, such as testicular EVs, prostasomes, and epididymosomes, have become important modulators of oocyte activation, sperm maturation, capacitation, acrosome stability, motility, and early embryonic development. This study aimed to evaluate the potential diagnostic and translational uses of sperm-associated extracellular vesicles (EVs) in male infertility and assisted reproduction, while also consolidating recent insights on their origins, composition, and functional significance. Methods: A focused narrative search of PubMed (2000–2025) was conducted using backward and forward citation tracking. Studies that qualified included human clinical cohorts, functional sperm extracellular vesicle tests, and omics analyses using MISEV-aligned extracellular vesicle isolation and characterisation methodologies. When human mechanistic understanding was constrained, knowledge from animal research was selectively integrated. Results: The cargo signatures specific to the source identified in sperm-derived and seminal EVs encompass proteins, small RNAs, lipids, and enzymatic modules that govern sperm maturation, capacitation, acrosome reaction, redox balance, calcium signalling, zona binding, and DNA integrity. Density-resolved seminal extracellular vesicle subfractions (EV-H/EV-M/EV-L) have unique functional and proteomic characteristics linked to progesterone-induced hyperactivation, oxidative stress, and motility. Asthenozoospermia and oligoasthenoteratozoospermia are associated with changes in extracellular vesicle composition, reduced embryonic developmental potential, compromised oocyte activation (related to PLCζ), and increased sperm DNA fragmentation. Numerous EV-related miRNA and protein signatures may predict TESE results, identify functional sperm anomalies not recognised by conventional semen analysis, and differentiate between obstructive and non-obstructive azoospermia. Conclusions: The available findings indicate that sperm-derived extracellular vesicles are significant functional regulators of sperm physiology and may serve as valuable non-invasive indicators for male infertility. The standardisation of EV isolation, characterisation, and clinical validation is essential prior to widespread use; nonetheless, their integration into liquid biopsy methods and assisted reproductive technology processes represents a significant improvement. Full article

Background/Objectives: Ultrasound-guided transvaginal follicular aspiration is a central procedure in in vitro fertilisation (IVF), aiming to collect oocytes necessary for the success of assisted reproduction treatments. Follicular flushing, proposed in the absence of cumulo-oocyte complex (COC) at initial aspiration, remains controversial regarding its real impact on oocyte quality and pregnancy rates. Methods: In this controlled study, conducted in 274 patients, we evaluated the effects of systematic follicular flushing up to 10 washes with a standardised medium (pH 7.3 ± 0.1; 37.2 ± 0.2 °C) on oocyte yield, oocyte morphology, embryo kinetics and clinical outcomes. Results: Flushing resulted in an additional 38% recovery of COCs, mostly between the second and fifth flush, with no significant increase in oocyte dysmorphisms or major embryonic abnormalities. A slight increase in slow cleavages was observed (27% vs. 23%, p = 0.04), as well as a lower oocyte maturation rate when ovulation was triggered by Ovitrelle alone. Clinically, pregnancy rates per transfer were comparable between groups (33.27% without flushing vs. 32.86% with flushing; p = 0.67), as were miscarriage rates (9.11% vs. 8.69%; p = 0.81). Conclusions: These results indicate that follicular flushing, when applied according to a standardised protocol, significantly increases oocyte yield without compromising oocyte morphological quality or embryonic development potential. Although the observed clinical benefits remain modest, this approach could constitute a relevant complementary strategy, particularly in patients with poor ovarian response or in the context of poor initial recovery. However, the controlled but non-randomised nature of this study requires cautious interpretation of the findings. Larger randomised trials, integrating dynamic assessment technologies, such as time-lapse imaging or oocyte transcriptomic analysis, are needed to refine the clinical indications of this technique and explore its underlying biological mechanisms. Full article

Objectives: Oocyte quality is crucial for female fertility, but the underlying molecular mechanisms remain unclear. This study investigates the non-canonical role of the telomerase RNA protein (TERP), whose function in oogenesis is unknown, in safeguarding female gamete quality. Methods: We used gain-of-function (AT) and loss-of-function (D7) mutant mouse lines to assess oocyte quality via morphological and molecular analyses. Key methods included immunofluorescence of meiotic spindles, Western blotting for the autophagy marker LC3B, and qRT-PCR to quantify the perinatal ovarian reserve. Results: Both AT and D7 mutations caused severe meiotic spindle abnormalities, including aberrant morphology and increased size. The D7 mutation, in particular, led to impaired cytoplasmic maturation and reduced autophagy levels in oocytes. Furthermore, loss of TERP function resulted in an abnormally large ovarian reserve in newborn females, which correlated with decreased expression of autophagy and lysosomal markers in the newborn ovary. Conclusions: This study establishes a novel, non-canonical function for TERP as a crucial regulator of oocyte quality. TERP dysregulation compromises meiotic integrity and oocyte maturation by disrupting lysosome-dependent autophagy. Full article

The brown planthopper, Nilaparvata lugens, a major rice pest, harbors yeast-like symbionts (YLSs) that form mutualistic relationships with the host, significantly influencing its development and reproduction. As proteasome subunits play major roles in the assembly and functional maintenance of the proteasome, but their regulation on the YLSs in N. lugens are unclear. In this study, we analyzed the spatiotemporal and temporal expression patterns of five N. lugens proteasome subunits (NlPSMA2, NlPSMB5, NlPSMC4, NlPSMD10, NlPSMD13), and further verified their functions on the transovarial transmission of YLSs, in addition to the reproduction of N. lugens, based on RNA interference (RNAi). The results showed that NlPSMA2, NlPSMB5, NlPSMC4, NlPSMD10, and NlPSMD13 were highly expressed in ovarian follicular cells of N. lugens upon sexual maturation. After suppressing the expression of these genes by RNAi, N. lugens exhibited a shortened lifespan, abnormal pear-shaped follicles, and impaired oviposition capacity, but the number of YLSs in the whole body and the oocyte of N. lugens were significantly increased. These results indicate that the proteasome subunits play crucial roles in the reproduction of N. lugens and the transovarial transmission of its YLSs. Full article

A retrospective cohort study was conducted comparing conventional intracytoplasmic sperm injection (ICSI) with a pre-catching sperm (PCS)-ICSI technique. Cases with at least 0.5 million motile sperm and 5 mature oocytes were included. Conventional ICSI involves simultaneous loading of sperm and oocytes onto the dish, followed by identification, immobilization, and loading of sperm into pipettes for oocyte injection. In the PCS-ICSI technique, suitable sperm were identified and immobilized prior to oocyte loading onto the dish, thus reducing the oocyte exposure time. Variables of interest included rate of fertilized and degenerated oocytes, abnormal fertilization, quality blastocyst formation, and pregnancy outcomes. Statistical analysis utilized Student’s t-test and Fisher’s Exact Test. Our study included 330 PCS-ICSI and 287 conventional ICSI cases. Female age, BMI, AMH, total number of collected oocytes, and rate of abnormal fertilization were similar between groups. The PCS-ICSI group demonstrated an increased rate of oocyte fertilization (84.0% vs. 79.3%, p < 0.001), good quality blastocyst formation (54.9% vs. 48.0%, p < 0.001), and a lower rate of oocyte degeneration (1.4% vs. 3.5%, p < 0.001). Positive pregnancy rate, clinical pregnancy, and live birth rate were similar between groups. The expansion of this technique resulted in increased oocyte fertilization and good quality blastocyst formation, and decreased oocyte degeneration. Further studies will evaluate the effectiveness of this technique in broader patient populations. Full article

Infertility affects 17.5% of couples worldwide, and is notably caused in females by ovarian disorders that impact follicle development and oocyte maturation. Polycystic ovary syndrome (PCOS), affecting 8 to 13% of women of reproductive age, is a leading cause of anovulation and is characterized by arrested antral follicle development before the preovulatory stage. Reproductive issues of PCOS are often exacerbated in overweight or obese women. Obesity, which is increasingly prevalent worldwide, is also associated with anovulation, primarily due to defects in oocyte quality. Oocyte quality and competence depend on the proper activity of granulosa cells (GCs), which surround and support the oocyte. GCs produce key factors, such as 17β-estradiol, which regulate follicle growth and oocyte maturation. They also provide essential metabolic support for oocyte maturation and play a critical role in ovulation and fertilization. This review outlines the physiological role of GCs in follicle growth and maturation and explores recent advancements in understanding GCs’ molecular and physiological dysfunctions that contribute to infertility in PCOS and obesity. Improved knowledge of the endocrine mechanisms underlying follicular abnormalities in these conditions could help to predict oocyte competence and enhance assisted reproduction outcomes. Full article

Background/Objectives: Cellular oxidative stress is crucial for GV stage oocyte vitrification quality. PI3K and the aquaporin family have been shown to facilitate various cellular processes related to redox homeostasis and energy balance; yet, the mechanisms underlying the involvement of aquaporin 7 (AQP7) in vitrified oocyte oxidative stress remain unclear. The purpose of the present investigation was to evaluate the role of AQP7 in vitrified oocytes and the mechanisms involved. Methods: AQP7 inhibitors were employed to investigate the effect of AQP7 on oxidative stress in mouse-vitrified oocytes, whereas PI3K activators were harnessed to ascertain whether AQP7 serves as a functional molecule involved in this process. Results: Our results indicate that AQP7 inhibition in vitrified oocytes results in a significant decrease in glutathione (GSH) levels associated with cellular oxidation and an elevation in H₂O₂ levels. This was accompanied by exacerbated mitochondrial dysfunction, weakened cytoskeletal proteins, accelerated early apoptosis. Consequently, both survival and maturation rates were markedly reduced. Interestingly, PI3K/AKT activation increased AQP7 expression, restored abnormal mitochondrial distribution, as well as calcium homeostasis, and rescued the oocyte survival/maturation rate. Conclusions: Our results provide new insights indicating that PI3K/AKT/AQP7 decreases oxidative stress by regulating mitochondrial morphology, function, and distribution, thereby rescuing oocyte maturation in vitrification. Full article

This study aimed to compare the morphometry, morphology, and maturation capacity of cattle oocytes subjected to vitrification using different vitrification and maturation media. In Experiment 1, a total of 900 oocytes were divided into three groups: (1) matured before vitrification, (2) non-vitrified, and (3) vitrified as immature oocytes using the straw vitrification method. Morphometric parameters, including oocyte diameter, ooplasm, zona pellucida width (ZPW), granulosa cell width (GRSW), and zona pellucida-granulosa cell width (ZP GRSW), were measured (µm) before and after cryopreservation. In Experiment 2, the maturation capacity of three in vitro maturation (IVM) media (VitroMat-Protect™, BO-IVM™, and TCM199) was evaluated based on cumulus–oocyte complex (COC) expansion and polar body (PB) extrusion. Morphological abnormalities such as fragmented polar bodies (FPBs), large vacuoles (LVs), degenerated oocytes (DOs), and cracked cytoplasm (CC) were recorded. While vitrification did not significantly affect the oocyte diameter, ooplasm, or ZPW, it significantly reduced the GRSW and ZP GRSW. BO-IVM™ supported the highest COC expansion rate, while TCM199 had the lowest. Among vitrified oocytes, the highest PB extrusion rates were observed in BO-IVM^TM (35.14 ± 5.01) and Vitromat-Protect^TM (24.60 ± 5.67) as compared to TCM199 (18.44 ± 8.00; p < 0.05). Oocytes with higher CC rates were observed in VitroMat-Protect™ (24.50 ± 10.53) and BO-IVM™ (31.42 ± 7.32) as compared to TCM199 (18.70 ± 7.04). In conclusion, the vitrification process affects the granulosa cells in both vitrified immature and mature oocytes. BO-IVM^TM and VitroMat-Protect^TM supported better oocyte maturation than TCM199, although vitrification increased FPB and CC rates. Full article

Mercury, a prevalent heavy metal, negatively impacts oocyte maturation. However, the exact mechanism by which methylmercury chloride (MMC) affects this process remains elusive. The present study found that MMC administration triggered meiotic failure in oocytes by disrupting cumulus cell expansion, leading to compromised spindle apparatus and altered chromosomal architecture, which are crucial for oocyte development. This disruption is characterized by abnormal microtubule organization and defective chromosome alignment. Additionally, MMC exposure caused oxidative stress-induced apoptosis due to mitochondrial dysfunction, as indicated by decreased mitochondrial membrane potential, mitochondrial content, mitochondrial DNA copy number, and adenosine triphosphate levels. Proteomic analysis identified 97 differentially expressed proteins, including P62, an autophagy marker. Our results confirmed that MMC induced autophagy, particularly through the hyperactivation of the mitochondrial autophagy to remove damaged and normal mitochondria. The mitochondrial reactive oxygen species (ROS) scavenger Mito-TEMPO alleviated oxidative stress and mitochondrial autophagy levels, suggesting that mitochondrial ROS initiates this autophagic response. Notably, MMC activates mitochondrial autophagy via the monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signal pathway due to mitochondrial dysfunction. In vivo studies in mice revealed that MMC exposure decreased reproductive performance, attributed to excessive mitochondrial autophagy leading to reduced oocyte quality. Overall, these findings demonstrate that MMC exposure impairs oocyte maturation via the hyperactivation of mitochondrial autophagy induced by mitochondrial dysfunction. Full article