Oocyte Development Research Articles

Effect of biphasic in vitro maturation (CAPA-IVM) on EGF receptor and embryo development of prepubertal goat oocytes according to follicle size

Oocytes spontaneously resume meiosis following their liberation from follicles, preventing full competence acquisition. Biphasic IVM (CAPA-IVM) maintains oocytes in meiotic arrest to improve developmental competence, and it specially affects poorly developed oocytes. We assessed the effect of CAPA-IVM on oocytes from small (<3mm) and large (>3mm) follicles of prepubertal goats. Oocytes were cultured for 6h in pre-IVM with C-type natriuretic peptide (CNP) and estradiol as meiotic inhibitors, and germinal vesicle (GV) rate and chromatin configuration were assessed. Then, oocytes were cultured in conventional IVM (c-IVM) or CAPA-IVM (pre-IVM + c-IVM) and EGF receptor (EGFR) protein expression, intra-oocyte ROS and blastocyst development were assessed. GV rate was higher in CNP groups than control (69% vs 28%, and 67% vs 31%, small and large follicles, respectively), but GV chromatin configuration was similar. In large follicles, EGFR expression was higher in oocytes and cumulus cells after CAPA-IVM, and ROS levels were lower. In small follicles these differences were not observed. c-IVM and CAPA-IVM produced similar blastocyst rates in small (3.7% vs 2.6%, respectively) and large follicles (8.3% vs 2.5%). Overall, CAPA-IVM enhanced EGFR expression for EGF peptide signalling and antioxidant capacity in oocytes from large follicles but oocytes from small follicles were too immature to benefit from it.

Human oocyte zona pellucida abnormalities: evaluation of clinical impact for different zona pellucida abnormalities and role of using assisted hatching.

Zona pellucida (ZP) plays an important role in oocyte development and fertilisation, as well as in early embryo development. However, there is currently no exploration of systematic categorising and clinical treatment measures for patients with abnormal ZP, especially the fast and easy method that can be used clinically. In this study, 185 patients with abnormal ZP (ZPA) and 222 patients with normal ZP (ZPN) were enrolled and analysed. Patients with ZPA exhibited altered hormone levels and lower laboratory outcomes in in vitro fertilisation (IVF), such as reduced MII rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate compared to ZPN group. ZPA patients were sub-categorised into ZPA-A/B/C/D group according to the status of oocyte polar body and the width of perivitelline space (PVS). There are also differences in the degree of sperm binding to ZP derived from different ZPA patients and the elasticity of the oocyte membrane. ZPA subgroup analysis revealed further disparities in various IVF parameters and pregnancy outcomes. In addition, by performing different treatments on oocytes derived from ZPA patients, we found that ZP assisted hatching before the first oocyte cleavage on D1 of embryonic development in the ZPA-A/B groups and before blastocyst expansion on D4 of embryonic development in the ZPA-C/D groups were beneficial to improve embryonic development. The degree of the impact on clinical outcomes is correlated with the types of ZPA, and laser-assisted hatching of the ZP helps to improve embryonic development in patients with ZPA.

EZH1/2 plays critical roles in oocyte meiosis prophase I in mice

Backgroudabnormalities or defects in oocyte meiosis can result in decreased oocyte quality, reduced ovarian reserve, and female diseases. However, the mechanisms of oocyte meiosis remain largely unknown, especially epigenetic regulation. Here, we explored the role of EZH1/2 (histone methyltransferase of H3K27) in mouse oocyte meiosis by inhibiting its activity and deleting its gene.Resultswith embryonic ovary cultured in vitro, EZH1/2 was demonstrated to be essential for oocyte development during meiosis prophase I in mice. Activity inhibition or gene knockout of EZH1/2 resulted in cell apoptosis and a reduction in oocyte numbers within embryonic ovaries. By observing the expression of some meiotic marker protein (γ-H2AX, diplotene stage marker MSY2 and synapsis complex protein SCP1), we found that function deficiency of EZH1/2 resulted in failure of DNA double-strand breaks (DSBs) repair and break of meiotic progression in fetal mouse ovaries. Moreover, Ezh1/2 deficiency led to the suppression of ATM (Ataxia Telangiectasia Mutated kinase) phosphorylation and a decrease in the expression of key DNA repair proteins Hormad1, Mre11, Rad50, and Nbs1 in fetal mouse ovaries, underscoring the enzyme’s pivotal role in initiating DNA repair. RNA-seq analysis revealed that Ezh1/2-deletion induced abnormal expression of multiple genes involved into several function of oocyte development in embryonic ovaries. Knockout of Ezh1/2 in ovaries also affected the levels of H3K9me3 and H4K20me2, as well as the expression of their target genes L3mbtl4 and Fbxo44.Conclusionsour study demonstrated that EZH1/2 plays a role in the DSBs repair in oocyte meiosis prophase I via multiple mechanisms and offers new insights into the physiological regulatory role of histone modification in fetal oocyte guardianship and female fertility.

High-altitude hypoxia exposure alters follicular metabolome and oocyte developmental potential in women.

To explore the effects of high-altitude hypoxia on the microenvironment of oocyte development and fertilization potential, we compared the metabolomic patterns of follicular fluid from women living in different altitude areas and traced their oocyte maturation and subsequent development. A total of 315 clinical cases were collected and divided into three groups according to their residence altitudes: 138 cases in low-altitude (< 2300m) group, 100 cases in middle-altitude (2300-2800m) group and 77 cases in high-altitude (> 2800m) group. The clinical outcomes were statistically estimated, including hormonal level, oocyte maturation, in vitro fertilization, and embryo development. Meanwhile, a metabolomic analysis was performed on the follicular fluid of women from different groups using ultra-high-performance liquid chromatography and high-resolution mass spectrometry and differential metabolites were analyzed through the KEGG pathway. The clinical data indicated that the physical condition and reproductive hormone secretion were similar among different groups. Although personalized gonadotropin-releasing hormone strategies were applied, the numbers of antral follicles and obtained oocytes were not impacted by the residence altitude change. In in vitro culture, the maturing rate, fertility rate and cleavage rate of high-altitude group were compared with the other groups. However, the rates of high-quality embryo, formative blastocyst, and available blastocyst were gradually decreased with the rise of residence altitude. Metabolome analysis identified 1193 metabolites in female follicular fluid. Differential analysis indicated that metabolic components in follicular fluid were remarkably changed with the elevation of residence altitude. These differential metabolites were closely related with amino acid metabolism, protein digestion and absorption, oocyte meiosis and steroid biosynthesis. The residence altitude alters the microenvironment of follicular fluid, which could damage the oocyte developmental potential. This study provides diagnostic basis and therapeutic targets for research on female oocyte and embryo development.

Insights into Adaption and Growth Evolution: Genome–Wide Copy Number Variation Analysis in Chinese Hainan Yellow Cattle Using Whole–Genome Re–Sequencing Data

Copy number variation (CNV) serves as a crucial source of genomic variation and significantly aids in the mining of genomic information in cattle. This study aims to analyze re–sequencing data from Chinese Hainan yellow cattle, to uncover breed CNV information, and to elucidate the resources of population genetic variation. We conducted whole–genome sequencing on 30 Chinese Hainan yellow cattle, thus generating 814.50 Gb of raw data. CNVs were called using CNVnator software, and subsequent filtering with Plink and HandyCNV yielded 197,434 high–quality CNVs and 5852 CNV regions (CNVRs). Notably, the proportion of deleted sequences (81.98%) exceeded that of duplicated sequences (18.02%), with the lengths of CNVs predominantly ranging between 20 and 500 Kb This distribution demonstrated a decrease in CNVR count with increasing fragment length. Furthermore, an analysis of the population genetic structure using CNVR databases from Chinese, Indian, and European commercial cattle breeds revealed differences between Chinese Bos indicus and Indian Bos indicus. Significant differences were also observed between Hainan yellow cattle and European commercial breeds. We conducted gene annotation for both Hainan yellow cattle and European commercial cattle, as well as for Chinese Bos indicus and Indian Bos indicus, identifying 206 genes that are expressed in both Chinese and Indian Bos indicus. These findings may provide valuable references for future research on Bos indicus. Additionally, selection signatures analysis based on Hainan yellow cattle and three European commercial cattle breeds identified putative pathways related to heat tolerance, disease resistance, fat metabolism, environmental adaptation, candidate genes associated with reproduction and the development of sperm and oocytes (CABS1, DLD, FSHR, HSD17B2, KDM2A), environmental adaptation (CNGB3, FAM161A, DIAPH3, EYA4, AAK1, ERBB4, ERC2), oxidative stress anti–inflammatory response (COMMD1, OXR1), disease resistance (CNTN5, HRH4, NAALADL2), and meat quality (EHHADH, RHOD, GFPT1, SULT1B1). This study provides a comprehensive exploration of CNVs at the molecular level in Chinese Hainan yellow cattle, offering theoretical support for future breeding and selection programs aimed at enhancing qualities of this breed.

In vitro gametogenesis: Towards competent oocytes: Limitations and future improvements for generating oocytes from pluripotent stem cells in culture.

Production of oocytes from pluripotent cell cultures in a dish represents a new paradigm in stem cell and developmental biology and has implications for how we think about life. The spark of life for the next generation occurs at fertilization when sperm and oocyte fuse. In animals, gametes are the only cells that transmit their genomes to the next generation. Oocytes contain in addition a large cytoplasm with factors that direct embryonic development. Reconstitution of mouse oocyte and embryonic development in culture provides experimental opportunities and facilitates an unprecedented understanding of molecular mechanisms. However, the application of in vitro gametogenesis to reproductive medicine or infertility treatment remains challenging. One significant concern is the quality of in vitro-derived oocytes. Here, we review the current understanding and identify limitations in generating oocytes in vitro. From this basis, we explore opportunities for future improvements of the in vitro approach to generating high-quality oocytes.

Central role of squid gene during oocyte development in the Hemiptera Rhodnius prolixus

Oocyte polarity establishment is a conserved and crucial phenomenon for embryonic development. It relies on the precise spatial localization of maternal factors deposited during oocyte development, which is essential for establishing and maintaining cell polarity and subsequently specifying embryonic axes. The heterogeneous nuclear ribonucleoprotein (hnRNP) encoded by the squid (sqd) gene has been implicated in mRNA localization and embryonic axis establishment in Drosophila melanogaster. Comparative genomics allowed for the identification of a homologue in Rhodnius prolixus. In this study, we investigated the function of Rp-sqd during oogenesis and early embryonic development. We observed persistent expression of Rp-sqd during oocyte development, with localization in the cytoplasm of ovary germarium and growing oocytes in previtellogenic and vitellogenic stages. A Parental RNA interference (RNAi) experiment targeting Rp-sqd resulted in female sterility. The ovaries showed disrupted oocyte development, disarray of follicular epithelium, and affected nurse cells integrity. Immunostaining and microscopic techniques revealed microtubule disarray and a reduction in the presence of organelles in the trophic cords that connect the germarium with the oocytes. The Rp-sqd depletion impacted the transcript expression of maternal mRNAs involved in apoptosis, axis formation, oogenesis, and cytoskeleton maintenance, indicating a pleiotropic function of Rp-sqd during oogenesis. This study provides new insights into the genetic basis of R. prolixus oogenesis, highlighting the crucial role of Rp-sqd in oocyte development, fertility, and germarium integrity. These findings contribute to our understanding of insect developmental processes, provide a foundation for future investigations into reproduction, and reveal the regulatory mechanisms governing the process.

Early apoptosis detection in canine granulosa cells through the analysis of BCL-2 and BAX proteins during the follicular development associated with oocyte maturation

The objective of this study was to investigate the early follicular apoptosis in canine ovarian follicles by examining the expression of anti-apoptotic BCL-2 and pro-apoptotic BAX proteins throughout the estrous cycle associated with oocyte maturation. Follicular cells from preantral and antral follicles of varying sizes were isolated and grouped based on follicle type and estrous phase. Antral follicles underwent flow cytometry analysis, whereas preantral follicles were subjected to Western blotting. The meiotic capacity of oocytes from these different follicle types was evaluated through in vitro maturation. Statistical analysis included ANOVA and Duncan’s test. Results showed fluctuations in BCL-2 and BAX levels across different follicular stages and estrous phases. BCL-2 levels increased (P<0.05) with follicular development in antral follicles, particularly during estrus, while BAX exhibited variations peaking (P<0.05) during estrus. The BCL-2/BAX ratio in antral follicles was higher (P<0.05) in estrus and diestrus compared to anestrus and proestrus. Additionally, BCL-2 and BAX proteins were detected in preantral follicles, with varying expression levels (P<0.05) across estrous phases. The BCL-2/BAX ratio in preantral follicles was highest (P<0.05) during anestrus and estrus and decreased (P<0.05) in proestrus and diestrus. Oocytes from preantral follicles did not reach the MII stage, regardless of the levels of BCL-2/BAX. Conversely, oocytes obtained from large follicles during estrus showed the highest (P<0.05) maturation percentages, which were associated with the highest BCL-2/BAX ratio. These findings provide insights into the dynamic patterns of BCL-2 /BAX in canine follicles across the estrous cycle, shedding light on their potential roles in oocyte development.

3D-printed scaffolds with controlled-releasing compounds for ectopic activation of dormant ovarian follicles

Throughout a woman&amp;rsquo;s reproductive life, hundreds of functioning follicles are activated for development, while thousands of dormant follicles remain in the ovaries. Dormant follicle activation in vitro is an effective clinical strategy for women with fertility needs who suffer from ovarian dysfunction. However, activating dormant follicles in vivo is still a challenge due to difficulties such as delivering stimulators to local sites. Here, we developed a compound-preloaded microporous scaffold by combining three-dimensional (3D) printing techniques with pharmacological activators to support and stimulate the activation and development of primordial follicles. The gelatin/alginate composite scaffolds exhibited exceptional mechanical properties and biological compatibility, effectively supporting the survival of ovarian granulosa cells for more than 7 days, which is essential for oocyte development. Furthermore, the ovarian tissue-scaffold complex successfully survived after transplantation under the mouse kidney capsule, demonstrating its excellent biocompatibility. After pre-mixing widely used clinical activators into the bio-ink, the scaffold had the ability to gradually release the mixture of compounds, effectively activating primordial follicles. By transplanting the ovary-scaffold complex containing activators into the mouse abdominal subcutaneous pocket, dormant follicles could be activated subcutaneously and developed into growing follicles. The number of growing follicles is approximately three times higher compared to the group without activators. In conclusion, by integrating biomaterials, activators, and 3D printing technology, we have developed 3D-printed biological scaffolds that can ectopically support primordial follicle activation and development in vivo. This novel approach could provide a promising strategy for treating ovarian insufficiency and endocrine disorders in the clinic, without the need for in situ ovarian tissue grafting.

EB-SUN, a new microtubule plus-end tracking protein in Drosophila.

Microtubule (MT) regulation is essential for oocyte development. In Drosophila, MT stability, polarity, abundance, and orientation undergo dynamic changes across developmental stages. In our effort to identify novel microtubule-associated proteins that regulate MTs in the Drosophila ovary, we identified a previously uncharacterized gene, CG18190, whichencodes a novel MT end-binding (EB) protein, which we propose to name EB-SUN. We show that EB-SUN colocalizes with EB1 at growing MT plus-ends in Drosophila S2 cells. Tissue-specific and developmental expression profiles from Paralog Explorer reveal that EB-SUN is predominantly expressed in the ovary and early embryos, while EB1 is ubiquitously expressed. Furthermore, as early as oocyte determination, EB-SUN comets are highly concentrated in oocytes during oogenesis. EB-SUN knockout (KO) results in decreased MT density at the onset of mid-oogenesis (stage 7) and delays oocyte growth during late mid-oogenesis (stage 9). Combining EB-SUN KO with EB1 knockdown (KD) in germ cells significantly further reduces MT density at stage 7. Hatching assays of single protein depletion reveal distinct roles for EB-SUN and EB1 in early embryogenesis, likely due to differences in theirexpression and binding partners. Notably, all eggs from EB-SUN KO/EB1 KD females fail to hatch, suggesting partial redundancy between these proteins.

COX15 deficiency causes oocyte ferroptosis

Mitochondria play diverse roles in mammalian physiology. The architecture, activity, and physiological functions of mitochondria in oocytes are largely different from those in somatic cells, but the mitochondrial proteins related to oocyte quality and reproductive longevity remain largely unknown. Here, using whole-exome sequencing data from 1,024 women (characterized by oocyte maturation arrest and degenerated or morphologically abnormal oocytes) and 2,868 healthy controls, we performed a population and gene-based burden test for mitochondrial genes and identified a candidate gene, cytochrome c oxidase assembly protein 15 (COX15). We report that biallelic COX15 pathogenic variants cause human oocyte ferroptosis and female infertility in a recessive inheritance pattern. COX15 variants impaired mitochondrial respiration in Saccharomyces cerevisiae and led to reduced protein levels in HeLa cells. Oocyte-specific deletion of Cox15 led to impaired Fe2+ and reactive oxygen species homeostasis that caused mitochondrial dysfunction and ultimately sensitized oocytes to ferroptosis. In addition, ferrostatin-1 (an inhibitor of ferroptosis) could rescue the oocyte ferroptosis phenotype in vitro and ex vivo. Our findings not only provide a genetic diagnostic marker for oocyte development defects but also expand the spectrum of mitochondrial disorders to female infertility and contribute to unique insights into the role of ferroptosis in human oocyte defects.

Toxic effects of microplastic and nanoplastic on the reproduction of teleost fish in aquatic environments.

Microplastics and nanoplastics are widely present in aquatic environments and attract significant scholarly attention due to their toxicity, persistence, and ability to cross biological barriers, which pose substantial risks to various fish species. Microplastics and nanoplastics can enter fish through their digestive tract, gills and skin, causing oxidative damage to the body and adversely affecting their reproductive system. Given that fish constitute a crucial source of high-quality protein for humans, it is necessary to study the impact of microplastics on fish reproduction in order to assess the impact of pollutants on ecology, biodiversity conservation, environmental sustainability, and endocrine disruption. This review explores the reproductive consequences of microplastics and nanoplastics in fish, examining aspects such as fecundity, abnormal offspring, circadian rhythm, gonad index, spermatocyte development, oocyte development, sperm quality, ovarian development, and changes at the molecular and cellular level. These investigations hold significant importance in environmental toxicology.

Variability in spruce beetle (Coleoptera: Curculionidae, Scolytinae) adult diapause and evidence for oocyte development prior to winter in a Colorado population.

Diapause regulates seasonal insect life cycles and may be highly variable within and among populations due to genetic and environmental variability. Both types of variation may influence how populations respond plastically or evolutionarily to changing climates. We assessed diapause variability in spruce beetle Dendroctonus rufipennis Kirby (Coleoptera: Curculionidae, Scolytinae), a major forest pest whose life cycle timing is regulated by both prepupal and adult diapauses. Using mating studies and ovary dissections, we tested for variability in adult diapause within and between collection sites in Colorado and Wyoming, USA. Ovary morphology suggested that most females from both sites enter diapause prior to egg formation (oogenesis) when reared at warm temperatures. Though previous studies suggested that adult diapause is obligate, we found that a small proportion of females from both populations terminated diapause without winter chilling in the lab. Moreover, we found that most female beetles sampled at the Colorado field site had mature ovaries relatively early in the fall, suggesting that transient exposure to low temperatures may potentiate pre-winter reproductive development. Adult diapause may act primarily as a block to prevent offspring production late in the season but not necessarily as an overwintering phenotype. Overall, our data do not suggest imminent life cycle shifts mediated by adult diapause, but if the observed variability is heritable, diapause regulation may evolve in response to changing environmental conditions.

A Significant Correlation of Glutamine and Interlukin-6 with Pregnancy Rate in Women Undergoing ICSI

Background: The composition of follicular fluid (FF) is significantly influenced by metabolic factors, and the analyses of metabolites in FF could reveal the correlation between metabolites and oocyte quality, embryo development, and pregnancy outcome. FF provides nutrients and growth factors that promote oocyte growth, development, and maturation. Objective: To investigate the relationship between serum and FF glutamine and FF IL-6 levels and their influence on the pregnancy rate in women who are undergoing an ICSI treatment cycle. Materials and Methods: A prospective cross-sectional study was performed on 90 women aged 20- 44 years who underwent ICSI treatment from July 2023 to February 2024. Serum and follicular fluid collected on the day of oocyte pick-up were used as biological material. The embryological laboratory examined the retrieved follicular fluid and collected oocytes using stereomicroscopy. ELISA analysed serum, FF glutamine and FF IL-6. The ICSI method was utilized for fertilization. The pregnancy test is done by measuring serum BHCG. Statistical data processing was conducted using the software package SPSS 23. Results: There was a highly significant correlation between FF glutamine and FF IL-6 (p &lt; 0.001) and a positive correlation between FF glutamine and FF IL-6 with pregnancy rate ( p &lt; 0.001) (p &lt; 0.001 ). Conclusion The correlation of FF glutamine and FF IL-6 affects the pregnancy rate in women undergoing ICSI. FF glutamine and FF IL-6 can be considered predictors for pregnancy while serum glutamine has no significance.

Changes in Inflammatory Cytokines, Vascular Markers, Cell Cycle Regulators, and Gonadotropin Receptors in Granulosa Cells of COVID-19 Infected Women

Background: COVID-19 infection can negatively affect multiple organ systems, including the reproductive system. Previous research has indicated altered levels of inflammatory markers in the reproductive tissues of women with chronic diseases. This study aimed to assess the expression of inflammatory, vascular, cell cycle, and gonadotropin receptor genes in the granulosa cells and oocytes of women with recent COVID-19 infection undergoing Assisted Reproductive Technology (ART), compared to healthy controls. Materials and Methods: The study involved 15 women who had tested positive for COVID-19 within three months of ART treatment and 15 age-matched healthy women as controls. Granulosa cells were collected during oocyte retrieval, and RNA was isolated to analyze gene expression using quantitative real-time PCR. The evaluated genes included inflammatory cytokines (IL-1B, TNF-α, IL-6, IL-8), vascular genes (VEGF, ANGPT1), cell cycle regulators (FOXL2, Cyclin D1, Cyclin D2, KLF4), and gonadotropin receptors (LHCGR, FSHR). Results: Results showed significantly higher expression of inflammatory cytokines in the granulosa cells of COVID-19 positive women, including IL-1B (4.2-fold), TNF-α (3.8-fold), IL-8 (2.5-fold), and IL-6 (3.2-fold). Vascular genes VEGF and ANGPT1 were also overexpressed, while FOXL2 was downregulated and Cyclin D1/D2 were upregulated in the study group. However, LH and FSH receptor expression remained similar between both groups. Conclusion: The present study demonstrates altered gene expression of inflammatory cytokines, vascular factors and cell cycle regulators in granulosa cells and oocytes of COVID-19 positive women undergoing ART. The dysregulated molecular pathways could potentially impair folliculogenesis and oocyte development in SARS-CoV-2 infected individuals.

Molecular characterization and stage-dependent gene expression of gonadotropin receptors in Pacific bluefin tuna, Thunnus orientalis, ovarian follicles

To understand the physiological mechanisms by which pituitary-derived gonadotropins (Gths), follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) regulate asynchronous oocyte development, we investigated the function and expression of Fsh and Lh receptors (Fshr and Lhr, respectively) in Pacific bluefin tuna (PBT, Thunnus orientalis). As a first, we cloned the full-length cDNAs encoding PBT Fshr and Lhr. Recombinant PBT Fsh and Lh single-chain proteins were produced in abundance using stable CHO-DG44 cell lines and were subsequently purified from the culture medium, culminating in their yields being 87.0 and 88.2%, respectively. An in vitro reporter assay using homologous recombinant Gths revealed that PBT Fshr and Lhr responded strongly to their corresponding ligands in a dose-dependent manner, with no cross-activation over a wide range of concentrations. Moreover, quantitative expression analysis of Fshr and Lhr at the follicle level showed that fshr gene expression was highly upregulated in the ovarian follicles through vitellogenesis, while lhr expression was significantly upregulated and peaked in fully vitellogenic ovarian follicles. These findings suggest that asynchronous-type oocyte development is primarily attributed to the differential function and expression of Gthrs, rather than the ligand, in PBT.

Which is the current knowledge on man-made endocrine- disrupting chemicals in follicular fluid? An overview of effects on ovarian function and reproductive health.

The increase in female reproductive disorders, such as polycystic ovary syndrome, endometriosis, and diminished ovarian reserve that lead to subfertility and infertility, has encouraged researchers to search and discover their underlying causes and risk factors. One of the crucial factors that may influence the increasing number of reproductive issues is environmental pollution, particularly exposure to man-made endocrine-disrupting chemicals (EDCs). EDCs can interfere with the ovarian microenvironment, impacting not only granulosa cell function but also other surrounding ovarian cells and follicular fluid (FF), which all play essential roles for oocyte development, maturation, and overall reproductive function. FF surrounds developing oocytes within an ovarian follicle and represents a dynamic milieu. EDCs are usually found in biological fluids, and FF is therefore of interest in this respect. This narrative review examines the current knowledge on specific classes of EDCs, including industrial chemicals, pesticides, and plasticizers, and their known effects on hormonal signaling pathways, gene expression, mitochondrial function, oxidative stress induction, and inflammation in FF. We describe the impact of EDCs on the development of reproductive disorders, oocyte quality, menstrual cycle regulation, and their effect on assisted reproductive technique outcomes. The potential transgenerational effects of EDCs on offspring through animal and first-human studies has been considered also. While significant progress has been made, the current understanding of EDCs' effects on ovarian function, particularly in humans, remains limited, underscoring the need for further research to clarify actions and effects of EDCs in the ovary.

High Carbohydrate, Fat, and Protein Diets Have a Critical Role in Folliculogenesis and Oocyte Development in Rats.

To date, there is no comparative data on the effects of carbohydrates, fat, and proteins, which are macronutrients, on female reproductive functions. Therefore, in this study, we investigated the effects of diets enriched with carbohydrates, fats, and proteins on folliculogenesis and oocyte development in female rats. 21-day-old rats that were just weaned were divided into 4 groups: control, carbohydrate, fat, and protein. The control group was fed with standard chow and the carbohydrate, fat, and protein groups were fed diets enriched with 75% carbohydrate, 60% fat, and 50% protein for 11 weeks, respectively. It was found that high-fat and high-protein diets caused an increase in the estrous cycle length compared to carbohydrate group (p < 0.05). Graafian follicle number decreased in the protein group compared to the control (p < 0.05). However, the atretic follicle number was higher in the fat group compared to the control group (p < 0.05). In the carbohydrate group, Zp1 was found to be lower than the control and protein groups, Zp2 was found to be lower than the control, and Zp3 was found to be lower than the fat group (p < 0.05). While BMP15 was similar between groups (p > 0.05), GDF9 was lower in all diet groups compared to the control (p < 0.05). Foxo3a was lower in the protein group compared to carbohydrate and control (p < 0.05). GAS2 was found to be higher in the control group than the fat group, and higher in the carbohydrate group than the fat and protein groups (p < 0.05). FSH, LH, Progesterone, and E2 levels were higher in all three diet groups than in the control (p < 0.05). Also, significant differences were observed between the groups regarding adiponectin, resistin, and leptin levels. Taken together, high carbohydrate, fat, and protein intake are associated with impairment of the menstrual cycle, depletion of the developing follicle types, and altered expression of folliculogenesis-specific genes and hormones. Therefore, long-term macronutrient diets may result in shortened reproductive periods and reduced fertilization potential in females in the long run.

Female-specific mechanisms of meiotic initiation and progression in mammalian oocyte development.

Meiosis is regulated in sexually dimorphic manners in mammals. In females, the commitment to and entry into meiosis are coordinated with the developmental program of oocytes. Female germ cells initiate meiosis within a short time window during the fetal period and then undergo meiotic arrest until puberty. However, the genetic mechanisms underlying the orchestration of oocyte development and meiosis to maximize the reproductive lifespan of mammalian females remain largely elusive. While meiotic initiation is regulated by a sexually common mechanism, where meiosis initiator and Stimulated by Retinoic Acid Gene 8 (STRA8) activate the meiotic genes, the female-specific mode of meiotic initiation is mediated by the interaction between retinoblastoma (RB) and STRA8. This review highlights the female-specific mechanisms of meiotic initiation and meiotic prophase progression in the context of oocyte development. Furthermore, the downstream pathway of the RB-STRA8 interaction that may regulate meiotic arrest will be discussed in the context of oocyte development, highlighting a potential genetic link between the female-specific mode of meiotic entry and meiotic arrest.

The effect of cortisone on female zebrafish (Dania rerio): Reducing reproductive capacity and offspring survival rate

Cortisone is a naturally occurring corticosteroid hormone known for its wide range of anti-inflammatory and immunosuppressive effects, and it is commonly found in various aquatic environments. Previous reports have shown that cortisone can have significant negative impacts on fish; however, its specific effects on fish reproduction have not been thoroughly investigated. In this study, female adult zebrafish were exposed to 0.0 (control), 3.9, 40.2, and 377.9 ng/L of cortisone for 60 days, and multiple endpoints were evaluated. The results showed that as the concentration of cortisone increased, there was an increase in the percentage of perinuclear oocytes and a decrease in the proportion of late-stage oocytes, indicating a stagnation in oocyte development. Additionally, female zebrafish exposed to cortisone exhibited decreased attraction to males and reduced mating intimacy. Furthermore, exposure to cortisone resulted in changes in the development and behavior of zebrafish embryos. At cortisone concentrations of 3.9 and 40.2 ng/L, fewer eggs were laid and the survival rate of fertilized eggs decreased. These observed effects are associated with abnormal transcription levels of genes (Star, Cyp11a1, Cyp17, Cyp19a, Cyp11b, Hsd11β2, Hsd17β3) related to the HPG axis. These findings provided new insights into understanding potential environmental risks associated with corticosteroids.