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Oocyte

An oocyte is a female in mammals, serving as the precursor to the mature egg and arrested in the of I within ovarian follicles. It originates from oogonia during embryonic , undergoes growth surrounded by granulosa cells, and accumulates essential cytoplasmic components like enzymes, mRNAs, and organelles to support early embryonic . , the process of oocyte formation, begins in the fetal where oogonia proliferate mitotically to produce millions of primary oocytes that enter I but arrest at the diplotene stage until . At , hormonal signals such as (FSH) and (LH) trigger periodic maturation of select oocytes within developing follicles, leading to the resumption of I. This results in the formation of a secondary oocyte and the first through unequal , with the secondary oocyte retaining most of the ; the secondary oocyte then arrests at of II until fertilization. Upon , the secondary oocyte is released into the , where completes II, extruding the second and forming a mature haploid ovum capable of embryonic . Structurally, the oocyte features a large called the germinal vesicle in its immature state, a surrounding the plasma membrane, and an asymmetric cortex that reorganizes during maturation to facilitate fertilization. In humans, only a small fraction of the initial ~7 million oocytes survive to reproductive age, with approximately 400 ovulated over a woman's lifetime, highlighting the oocyte's and critical role in . Abnormalities in oocyte quality or quantity contribute to conditions like and age-related reproductive decline, underscoring its biological significance.

Formation

Origin in Primordial Germ Cells

Primordial germ cells (PGCs), the precursors to oocytes, are specified during early in the posterior region of the epiblast at the onset of , approximately during the second to third week of . This process is induced by bone morphogenetic proteins (BMPs), particularly BMP4 and BMP8b, secreted from extraembryonic tissues such as the visceral and extraembryonic , which signal to competent epiblast cells to adopt a fate. Key transcription factors, including BLIMP1 (encoded by ), PRDM14, and NANOS3, are essential for this specification and subsequent maintenance of PGC identity by repressing somatic differentiation genes and promoting germline-specific gene expression. Following specification, PGCs emerge near the adjacent to the and initiate toward the developing genital ridges. This begins around week 4 of gestation and involves PGCs traversing the and dorsal , guided by chemotactic gradients of the SDF-1 (also known as ) and its receptor , which provide directional cues and promote cell survival. By approximately week 6, PGCs arrive at the genital ridges, where they colonize the somatic gonad and begin proliferating mitotically. Upon reaching the genital ridges, PGCs undergo further proliferation to expand the germ cell population and differentiate into gonocytes, a transitional stage that occurs around week 8 of . In the context of ovarian development, these gonocytes exhibit sex-specific influenced by the XX chromosomal complement and ovarian somatic signals, setting the stage for their progression into oogonia. The maintenance of this proliferative and undifferentiated state in female gonads relies on the continued expression of core PGC genes such as BLIMP1, PRDM14, and NANOS3.

Development into Primary Oocytes

Following migration and colonization of the developing gonadal ridge by primordial germ cells (PGCs), these cells differentiate into oogonia within the ovarian cortex, initiating a phase of rapid proliferation. This proliferation occurs primarily between gestational weeks 8 and 20, during which oogonia undergo multiple rounds of to expand the germ cell population. The process is driven by key growth factors and signaling pathways that support in the fetal environment. The oogonial population reaches its peak of approximately 6-7 million cells around 16-20 weeks of gestation, establishing the maximum reserve before the transition to . This expansion is essential for forming the , though it is accompanied by early , where a significant portion of oogonia undergo due to incomplete breakdown or insufficient support from surrounding cells. By the end of this proliferative phase, the surviving oogonia prepare for meiotic entry. Between approximately 8 and 13 weeks of , begin entering I asynchronously, transforming into primary oocytes. This transition starts with premeiotic followed by leptotene and zygotene stages of I, ultimately arresting in the diplotene stage, where chromosomes form a characteristic "lampbrush" configuration. The primary oocytes remain in this dictyate (diplotene) arrest until much later in reproductive life, marking the onset of meiotic commitment and halting further mitotic divisions. As primary oocytes accumulate, they become encapsulated by invading pre-granulosa cells derived from the ovarian , forming primordial follicles by mid-gestation (around 20 weeks). This encapsulation involves the breakdown of nests and selective pairing of oocytes with squamous pre-granulosa cells, creating the basic follicular unit that constitutes the non-renewable . Throughout this period, intensifies, eliminating the majority of s through , resulting in approximately 1-2 million primordial follicles present at birth, which further declines to about 300,000–400,000 by . This substantial loss ensures only viable oocytes are preserved in the primordial pool.

Structure and Characteristics

Cytoplasmic Components

The oocyte is enriched with granules, also known as vitelline reserves, which serve as primary nutrient storage sites composed of , proteins, and to support embryonic post-fertilization. These granules vary significantly across ; for instance, amphibians exhibit abundant reserves that contribute to large, nutrient-rich eggs, whereas mammalian oocytes contain minimal , relying more on maternal provisions from the reproductive tract. The accumulation of drives the formation of a specialized cytoplasmic environment, including maternal mRNAs, ribosomes, and organelles, essential for early embryogenesis. The oocyte features an extensive network of (ER) and Golgi apparatus, which are crucial for protein synthesis, folding, and secretion during and maturation. The rough ER, studded with ribosomes, facilitates the translation of maternal mRNAs into proteins, while the smooth ER contributes to lipid synthesis and calcium storage, supporting metabolic demands. The Golgi apparatus, in turn, processes and packages these proteins for vesicular transport, undergoing dynamic reorganization during meiotic maturation to ensure proper intracellular trafficking. Cortical granules, specialized secretory vesicles located just beneath the oocyte plasma membrane, play a key role in preventing upon fertilization by releasing their contents in a calcium-dependent event known as the . These granules contain enzymes, such as proteases like ovastacin, and other factors that modify the , hardening the to block additional entry and ensure monospermic fertilization in mammals. Their distribution and translocation to the are tightly regulated during oocyte maturation across . In many , the oocyte cytoplasm establishes a distinct along the animal-vegetal , with the animal pole typically containing less and the vegetal pole enriched with reserves, which influences asymmetric patterns during early embryogenesis. This directs the formation of smaller blastomeres at the animal pole and larger ones at the vegetal pole, presaging fate specification in the . For example, in ascidian oocytes, this is firmly established during maturation, arresting in I and guiding subsequent developmental asymmetries.

Nuclear Features

The nucleus of the oocyte, known as the germinal vesicle during I meiotic arrest, contains decondensed configurations that facilitate transcription during oocyte growth and maternal mRNA stockpiling. In mammalian oocytes, exists in two main configurations: non-surrounded (NSN), with diffuse and transcriptionally active , and surrounded (SN), with more condensed and transcriptionally quiescent ; the latter predominates in fully grown oocytes competent for maturation. This decondensed state, in contrast to compact somatic , supports transcriptional activity essential for ribosomal biogenesis and developmental processes before quiescence in oocytes. A prominent feature of the oocyte is its large, transcriptionally active , which contrasts with the more compact nucleoli observed in cells and is dedicated to robust production of (rRNA). This enlarged , visible during the growth phase of , actively transcribes rRNA genes to support the massive accumulation of ribosomes required for early embryonic , with its tripartite structure including fibrillar centers, dense fibrillar components, and granular components facilitating rRNA processing. The high transcriptional activity of this ensures the synthesis of the majority of cellular RNAs, underscoring its role in preparing the oocyte for post-fertilization demands. The surrounding the oocyte is equipped with numerous complexes that enable the selective export of newly transcribed mRNAs to the , a process critical for storing maternal transcripts during meiotic arrest. These pores facilitate the translocation of mature mRNA ribonucleoprotein complexes through energy-dependent mechanisms, ensuring efficient communication between the transcriptionally active and the . To maintain the diplotene , the oocyte nucleus undergoes mediated by specific modifications, such as de and , which condense and silence certain genes while preserving transcriptional activity at key loci like lampbrush loops. These modifications, including enrichment and reduced /H4 , help regulate meiotic progression by stabilizing the arrested state and preventing premature resumption. This dynamic remodeling is essential for balancing transcriptional output with meiotic competence. The ribosomal subunits assembled in the are exported via these pores to contribute to cytoplasmic machinery, as detailed in maternal contributions.

Extracellular Associations

In fetal ovaries, oocytes initially form clusters known as oocyte nests, or germ cell cysts, where primordial germ cells proliferate mitotically without completing , resulting in interconnected syncytia linked by cytoplasmic bridges. This process is conserved across mammals, with nests fully established in mice by embryonic day 12.5 and in humans around the 13th week of . Nest breakdown follows, typically postnatal in mice and during the second (weeks 17–20) in humans, involving by pre-granulosa cells and of intercellular bridges by proteases, which isolates individual oocytes to enable primordial follicle assembly. Substantial germ cell loss accompanies this breakdown, with 30–80% of oocytes eliminated through mediated by proteins, potentially serving as a mechanism to remove defective cells and establish a viable primordial follicle reserve. Incomplete breakdown can lead to multi-oocyte follicles, which impair oocyte viability and reduce fertilization rates by up to 30% in mice. As follicles form, granulosa cells play a central role by enveloping oocytes and facilitating their development through close physical and signaling interactions. These somatic cells, derived from ovarian mesenchyme, proliferate in response to follicle-stimulating hormone (FSH), which binds receptors on granulosa cells to promote cell division, estrogen synthesis, and differentiation via pathways like WNT/β-catenin. Granulosa cells form gap junctions with the oocyte through transzonal projections, enabling bidirectional communication and nutrient transfer essential for folliculogenesis. They also exhibit responsiveness to luteinizing hormone (LH), which stimulates progesterone production in later stages, and insulin, which synergizes with FSH to enhance proliferation and steroidogenesis. This hormonal regulation ensures selective follicular growth, with granulosa cells providing structural support and a microenvironment that sustains oocyte quiescence until maturation. Within antral follicles, the oocyte is embedded in the cumulus-oocyte complex (COC), a specialized structure where cumulus cells—specialized granulosa cells—directly surround the oocyte and provide metabolic support. Cumulus cells metabolize glucose to pyruvate and transport (e.g., via SLC38A3) and , delivering these nutrients to the oocyte through s formed by 37 (GJA4) on transzonal projections. These junctions also propagate signaling molecules like cyclic AMP () and cyclic GMP (cGMP), maintaining meiotic arrest until an LH surge disrupts them, allowing maturation to resume. Oocyte-derived factors such as growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) regulate cumulus cell differentiation and expansion, producing hyaluronic acid-rich that facilitates and sperm access. The COC's integrity is critical for oocyte quality, as disruptions in communication impair maturation and reduce fertilization success in assisted . Surrounding the oocyte in the COC and follicle is the (), a porous matrix that mediates binding and protects the oocyte. Composed primarily of four —ZP1, ZP2, ZP3, and ZP4—in humans and three—ZP1, ZP2, and ZP3—in mice (where ZP4 is a ), the ZP forms through of ZP2-ZP3 heterodimers into , crosslinked by ZP1 or ZP4, each containing a zona pellucida domain for structural assembly. Secretion occurs mainly from the oocyte, which synthesizes and packages ZPs into vesicles for extracellular release, with contributions from granulosa and cumulus cells via gap junctions to support matrix formation during . ZP3 serves as the primary receptor, binding via its O-linked oligosaccharides in a species-specific manner to induce the , while ZP2 reinforces binding during penetration; in ZP genes, such as ZP3 knockouts in mice, result in thin or absent ZP and . This matrix not only ensures selective fertilization but also organizes granulosa cells and aids in early embryonic development.

Maternal Contributions

Protection of Germ-Line DNA

Oocytes, arrested in I of for extended periods, employ specialized mechanisms to protect their germ-line DNA from damage, ensuring genomic integrity for . This is crucial during the prolonged dictyate , where oocytes are vulnerable to endogenous and exogenous insults that could lead to mutations or . Key strategies include efficient repair of programmed double-strand breaks (DSBs), activation of checkpoint pathways to eliminate defective cells, defenses against (ROS), and epigenetic controls to suppress mutagenic elements. During meiotic recombination in I, oocytes initiate DSBs via the SPO11 protein to facilitate pairing and crossover formation, which are subsequently repaired primarily through (HR). This pathway involves recruitment of recombinases like RAD51 and DMC1 to DSB sites, mediated by meiosis-specific factors such as the BRCA2-binding protein MEILB2, ensuring accurate repair using the as a template and minimizing error-prone alternatives. Impairment in this HR process, as seen in mutants lacking NBS1, leads to unresolved DSBs, disrupted , and oocyte loss, highlighting the pathway's role in maintaining DNA fidelity. To prevent propagation of genomic errors, oocytes activate checkpoint mechanisms that monitor DNA integrity and chromosome alignment, including precursors to the spindle assembly checkpoint (SAC). The DNA damage checkpoint, triggered by unresolved DSBs in late prophase I, eliminates oocytes with excessive damage (approximately 10 or more spontaneous breaks) through pro-apoptotic pathways involving BCL-2 family members like Puma, Noxa, and Bax, thereby averting aneuploidy. Additionally, non-canonical SAC functions in oocytes, involving proteins like Mad2 and BubR1, delay anaphase onset post-alignment to reduce segregation errors, though this checkpoint is less robust in mammalian oocytes compared to somatic cells. Aging exacerbates in oocytes due to accumulated ROS from mitochondrial activity, which can induce DNA strand breaks and base modifications; however, endogenous antioxidants like (GSH) mitigate this by scavenging ROS and supporting enzymes. GSH levels, synthesized via the , are particularly high in mature oocytes and decline with age, correlating with increased DNA damage and reduced ; supplementation or enhancement of GSH has been shown to improve oocyte quality in aged models by preserving DNA integrity. Epigenetic mechanisms further safeguard germ-line DNA by silencing transposable elements (TEs), which constitute a significant portion of the and pose a risk of if activated during oocyte arrest. In growing oocytes, de novo and piRNA-directed silencing target TEs like LINE-1 and IAP elements, preventing their transcription and mobility through histone modifications (e.g., ) and recruitment of repressive complexes. Disruption of this silencing, as in piRNA pathway mutants, leads to TE derepression, DNA breaks, and fetal oocyte attrition, underscoring its protective role against genomic instability.

Stored Molecular Machinery

The oocyte cytoplasm serves as a repository for maternally derived molecular components essential for initiating and sustaining early embryogenesis prior to zygotic genome activation (ZGA). These stockpiles include translationally dormant mRNAs, pre-synthesized proteins, organelles, and ribosomes, all of which are provisioned during to support developmental processes in the transcriptionally quiescent . This maternal endowment ensures rapid cellular responses to fertilization, including meiotic completion and the first mitotic divisions, without reliance on immediate embryonic transcription. Additionally, oocytes supply factors that enable correction of sperm DNA fragmentation upon fertilization, a process impaired in aged oocytes, contributing to reduced viability (as of 2025). Among the stored mRNAs, those encoding key regulators such as cyclin B1 and kinase are prominently featured, sequestered in cytoplasmic granules to prevent untimely . Cyclin B1 mRNA is asymmetrically localized in dormant granules during oocyte , with granule disassembly upon maturation signals enabling its into cyclin B1 protein, which partners with CDK1 to drive meiotic progression and early embryonic cycles. Similarly, mRNA undergoes regulated cytoplasmic , initiating in a temporally precise manner that amplifies MAPK signaling and reinforces cyclin B1 synthesis through positive feedback loops. These mechanisms highlight the oocyte's capacity to temporally control maternal gene expression products for coordinated developmental timing. Pre-formed proteins like CDK1 are also stockpiled in the oocyte, existing primarily as inactive complexes with cyclin B1 to maintain I arrest while remaining poised for activation. This stored CDK1 reservoir supports both meiotic resumption and the regulation of embryonic mitotic cycles, providing immediate catalytic activity for events critical to early development. The oocyte further inherits approximately mitochondria, each containing multiple copies of mtDNA, which collectively supply the embryonic mtDNA and generate ATP to meet high demands during oocyte maturation and preimplantation stages. These maternally contributed organelles are essential for and metabolic support until zygotic mitochondrial replication commences, underscoring their role in preventing deficits in the early . Ribosome biogenesis in the oocyte nucleolus during follicular growth yields a substantial reserve of assembled ribosomal subunits stored in the cytoplasm, enabling sustained of maternal mRNAs until ZGA. These maternal ribosomes, numbering in the hundreds of thousands per oocyte, facilitate protein across the initial embryonic cleavages, particularly in like mice where ZGA occurs at the 2-cell stage, thereby bridging the gap between maternal and zygotic transcriptional control.

Meiotic Regulation

Prophase I Arrest

In mammalian oocytes, prophase I arrest at the diplotene stage is primarily maintained by elevated intracellular levels of (cAMP), which activates (PKA) to phosphorylate and inhibit key meiotic regulators such as (MPF). This high , typically around 660 nM in arrested mouse oocytes, is sustained through communication with surrounding cells via gap junctions. Specifically, (cGMP) produced in granulosa and cumulus cells diffuses through these junctions into the oocyte, where it inhibits phosphodiesterase 3A (PDE3A), preventing cAMP hydrolysis. The production of cGMP in cumulus cells is driven by the natriuretic peptide signaling pathway, where natriuretic peptide precursor C (NPPC), secreted by the oocyte, binds to its receptor NPR2—a transmembrane guanylyl cyclase—on cumulus cell surfaces, catalyzing the conversion of GTP to cGMP. This NPR2-mediated elevation of cGMP (basal levels ~900 nM in follicle-enclosed oocytes) ensures continuous inhibition of PDE3A, thereby preserving oocyte cAMP and enforcing meiotic arrest. Disruption of this pathway, as seen in Npr2 knockout mice, leads to premature meiotic resumption and infertility, underscoring its essential role. During this prolonged arrest, the oocyte's undergoes reorganization into a surrounded () configuration, characterized by a rim of condensed encircling the nucleolus-like body, as observed via staining. This SN state correlates with global transcriptional silencing, as is excluded from , and it stabilizes the diplotene configuration to suppress additional recombination events beyond those completed in earlier I substages. Oocytes transitioning to SN typically exceed 40 μm in diameter and exhibit enhanced meiotic competence upon eventual resumption. Species-specific variations in arrest duration and regulation highlight evolutionary adaptations; in mammals like mice and humans, oocytes remain arrested for extended periods—from fetal stages through to , potentially lasting decades—relying heavily on interactions for maintenance. In contrast, many non-mammalian vertebrates, such as amphibians (e.g., ), exhibit shorter arrest phases, often weeks to months, supported more by intrinsic oocyte G-protein-coupled receptor signaling (e.g., via GPR3 homologs) independent of follicle cells. These differences influence reproductive strategies, with mammalian arrest allowing a stored pool of oocytes for cyclic .

Resumption of Meiosis

The resumption of meiosis in mammalian oocytes is primarily triggered by the preovulatory (LH) surge, which binds to receptors on surrounding granulosa cells and initiates a cascade of intercellular signaling events. This surge disrupts the mechanisms maintaining I arrest by promoting the of junctions between the oocyte and cumulus cells, thereby isolating the oocyte from inhibitory signals. Concurrently, LH stimulates the secretion of (EGF)-like peptides from mural granulosa cells, which activate (EGFR) signaling in cumulus cells. EGFR activation leads to a rapid decline in intra-oocyte (cAMP) levels through the upregulation of phosphodiesterases, such as PDE3A, which degrade cAMP and relieve its suppressive effect on meiotic progression. The drop in de-inhibits (MPF), a heterodimer of (CDK1) and B1, by allowing the activation of CDC25B and inhibition of Wee1B . activation drives the initial morphological changes of meiotic resumption, marked by germinal vesicle breakdown (GVBD), where the disassembles and condenses. Following GVBD, promotes the assembly of the microtubule-based meiotic , which aligns chromosomes for during I. This forms acentriolarly and migrates toward the oocyte cortex, ensuring proper chromosome capture and bipolar organization. Progression through I culminates in asymmetric , where the spindle's cortical positioning results in the extrusion of a small first containing half the chromatids, while the larger secondary oocyte retains most and organelles. This is mediated by actomyosin contractility and cortical , preserving cytoplasmic resources for subsequent embryonic . The secondary oocyte then arrests at II, awaiting fertilization. Oocyte competence for successful maturation is enhanced by oocyte-secreted factors such as growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), which promote cumulus cell expansion and support MPF/MAPK signaling to improve GVBD rates and overall meiotic efficiency.

Paternal Contributions

Genetic Input from Sperm

Upon fertilization, the haploid sperm delivers its genome into the oocyte cytoplasm, forming the male pronucleus, which must undergo rapid decondensation to integrate with the female pronucleus. The sperm chromatin arrives highly compacted by protamines rather than histones, a structure maintained through disulfide bonds and basic protein interactions. Oocyte-derived splicing kinase SRPK1 initiates decondensation by phosphorylating protamine 1 (PRM1) at specific serine residues (Ser9 and Ser43), which disrupts protamine-DNA interactions and promotes its eviction by nucleoplasmin 2 (NPM2), a chaperone abundant in the oocyte. This phosphorylation occurs within 1-1.5 hours post-fertilization and facilitates the deposition of maternal histones, particularly the variant H3.3 via the HIRA complex, enabling chromatin remodeling into a nucleosome-based structure compatible with the oocyte's genome. The decondensed male then migrates toward the female through microtubule-dependent mechanisms involving motors and actin-based forces at the fertilization cone, culminating in pronuclear (syngamy) to form the diploid zygotic . This typically occurs 8-12 hours after in mammals, varying by , ensuring synchronized before the first mitotic division. Disruptions in decondensation, such as mutations in PRM1 sites, severely impair pronuclear formation and reduce progression to the 2-cell stage by over 60%. The paternal genome remains transcriptionally silent immediately after , relying on maternal transcripts until zygotic genome activation (ZGA), a critical marking the onset of embryonic transcription. In mammals, ZGA timing varies by : it initiates in the late 1-cell stage for minor paternal gene expression in mice but is predominantly at the 8-cell stage in humans and other , where approximately 2,500 genes are activated to support further . This delay protects the paternal genome from premature transcription while maternal factors sustain early development. Genomic imprinting establishes parent-of-origin-specific expression patterns for the paternal DNA, influencing embryonic growth and development through epigenetic modifications acquired during . For instance, the () is preferentially expressed from the paternal due to differential at the imprinting control region (ICR) upstream of H19, a . On the paternal , at the H19 differentially methylated domain (H19DMD) prevents binding of the protein , allowing shared enhancers to activate Igf2 while repressing H19; conversely, the unmethylated maternal ICR blocks this access, silencing paternal-like expression. This mechanism ensures monoallelic Igf2 expression critical for fetal growth, with disruptions leading to imprinting disorders like Beckwith-Wiedemann syndrome. Post-fertilization, the physically separate pronuclei avoid inter-genomic recombination between paternal and maternal DNA until syngamy, preserving the integrity of each parental contribution during reprogramming. This spatial separation, maintained for several hours, prevents ectopic homologous recombination events that could introduce chromosomal rearrangements or allelic mismatches before diploid restoration. Oocyte surveillance mechanisms further ensure DNA lesions in the paternal genome, arising from protamine removal or demethylation, are repaired via non-homologous end joining rather than homologous recombination to minimize crossover risks with the maternal homolog.

Organelle Provision

Upon fertilization, the sperm delivers paternal centrioles that play a critical non-genomic role in organizing the zygote's . The proximal centriole, a structure, nucleates the formation of the sperm —a radial array that emerges shortly after sperm-oocyte fusion. This facilitates the migration of the pronuclei toward each other and establishes the foundation for the zygotic mitotic , which is indispensable for alignment and segregation during the first embryonic cleavage. Defects in sperm formation, often linked to centriolar abnormalities, can arrest development at the zygote stage, underscoring the centrioles' essential contribution to and early embryogenesis. The 's distal , an atypical structure lacking a full complement of , complements the proximal one by recruiting pericentriolar material (PCM) post-fusion. This PCM, partially contributed by the neck region and enriched with proteins like γ-tubulin and pericentrin, serves as a -organizing center (MTOC) to expand the and duplicate centrosomes for assembly. Although the paternal PCM is limited and insufficient for sustained divisions, it initiates nucleation, enabling the to transition from meiotic to mitotic organization before maternal PCM dominates. Sperm mitochondria represent another minimal paternal cytoplasmic contribution, but they are rapidly eliminated to preserve maternal mitochondrial dominance. Introduced in small numbers during fertilization, these organelles undergo ubiquitination, marking them for proteasomal degradation and subsequent engulfment by autophagosomes, which fuse with lysosomes for lysosomal breakdown. This selective mitophagy, conserved across mammals and other taxa, prevents paternal transmission and potential , ensuring uniparental inheritance from the oocyte. These contributions exhibit species-specific variations, particularly in centriole provision. In many mammals, including humans, sperm supply two functional centrioles, but in rodents like mice and numerous invertebrates such as sea urchins and nematodes, sperm centrioles are absent or degraded during spermiogenesis, necessitating de novo centriole assembly from maternal factors or atypical structures. Such adaptations highlight evolutionary divergence in organelle inheritance strategies while maintaining the zygote's capacity for microtubule organization.

Abnormalities

Chromosomal Errors

Chromosomal errors in oocytes primarily manifest as , resulting from inaccurate segregation during , with rates escalating markedly in women of due to prolonged arrest in I. These errors compromise the genetic integrity of the , increasing the risk of embryonic inviability or congenital disorders. Most aneuploidies originate in maternal I, where homologous chromosomes fail to disjoin properly, though errors can also occur in II. A key mechanism is during I, in which pairs do not separate to opposite poles, leading to gametes with extra or missing chromosomes. This process is responsible for common trisomies, such as trisomy 21 (), where approximately 90% of cases arise from maternal of , predominantly in I. The error stems from weakened attachments or assembly defects in aging oocytes, exacerbated by the extended duration of meiotic arrest. Cohesin degradation plays a central role in these segregation failures, as the protein complexes that hold together—such as those containing the meiosis-specific subunits REC8 and SMC1β—gradually deteriorate over time without replenishment in arrested oocytes. In older oocytes, this leads to weakened centromeric and arm cohesion, causing chiasmata to slip and chromosomes to misalign on the plate. Studies in models demonstrate that REC8 levels can drop by over 90% with age, directly correlating with elevated rates. Premature separation of (PSSC) represents a prevalent error mechanism in aged oocytes, particularly manifesting in II, where it accounts for up to 90% of errors in mouse models, leading to individual chromatids segregating independently rather than as intact dyads and yielding unbalanced gametes. This is linked to reduced centromeric protection by proteins like shugoshin 2 (SGO2). This contributes to the overall burden of single-chromatid aneuploidies observed in analyses. The incidence of aneuploidy in oocytes is approximately 20-25% in women under 35 years, increasing to 35-50% in those aged 35-39 years and exceeding 50% (up to 75%) by age 40, underscoring the impact of aging on meiotic fidelity. These rates are derived from comprehensive analyses of large oocyte cohorts via preimplantation genetic testing.

Developmental Defects

Oocyte , a hallmark of , involves progressive deterioration in oocyte quality characterized by reduced mitochondrial function and accumulation of (ROS). Mitochondria in aging oocytes exhibit impaired dynamics, including disrupted and processes, leading to decreased ATP production essential for meiotic progression and embryonic development. This dysfunction arises from factors such as NAD+ depletion and SIRT3 deficiency, which exacerbate and mtDNA damage, resulting in abnormalities, misalignment, and risks. Consequently, declines sharply, with live birth rates per oocyte dropping from approximately 26% in women under 35 to 1% in those over 42. ROS accumulation further promotes telomere shortening and , limiting the oocyte's developmental competence and contributing to age-related . Post-maturation decline in oocyte quality manifests in conditions like empty follicle syndrome (EFS), where no oocytes are retrieved despite adequate follicular growth and levels during ovarian . EFS, occurring in about 0.38% of assisted cycles, often stems from inadequate response to (hCG), potentially due to delayed receptor expression or suboptimal dosing, leading to failed oocyte release or maturation . In recurrent cases, underlying oocyte developmental disorders, such as I or abnormalities, indicate intrinsic quality decline post-maturation, possibly linked to genetic factors like mutations in LHCGR or genes. This syndrome impacts fertility by reducing oocyte yield, though adjusted protocols in subsequent cycles can achieve live births in up to 46.7% of affected patients, suggesting it does not always preclude future success. Teratoma formation represents a pathological outcome from parthenogenetic of oocytes, where unfertilized oocytes undergo spontaneous development without input, leading to tumorous growths. This , often triggered by premature calcium oscillations or cytoskeletal disruptions, initiates aberrant meiotic resumption and intrafollicular , resulting in benign ovarian teratomas containing tissues from all three layers due to pluripotent expansion. In model organisms like LT/Sv mice, high rates of such produce teratomas from blastocyst-stage parthenotes, while cases link similar events to ovarian teratomas via genetic analyses showing homozygous markers consistent with uniparental origin. These defects impair by depleting the through uncontrolled growth and highlight the risks of meiotic dysregulation in unovulated oocytes. Environmental factors, particularly endocrine disruptors like (BPA), contribute to developmental defects by diminishing oocyte reserves and compromising quality. BPA exposure accelerates primordial follicle atresia and premature recruitment, reducing antral follicle counts and overall , as evidenced by lower follicle numbers in women with higher urinary BPA levels during treatments. Mechanisms involve induction, in granulosa cells, and disrupted steroidogenesis, which impair oocyte maturation and cumulus expansion, leading to poorer IVF outcomes such as decreased oocyte yield and fertilization rates. Prenatal or chronic BPA exposure in animal models further demonstrates transgenerational effects on fertility, underscoring its role in accelerating ovarian aging and insufficiency.