JBRA Assist. Reprod. 2026 2026;00(0):00-00
REVIEW
doi: 10.5935/1518-0557.20260064
1Senior Clinical Support/Consultant Embryologist, Vitrolife Group, Sweden
2Department of Public Health, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
3Department of Gynecology and Obstetrics, Réseau Hospitalier Neuchâtelois, 2000 Neuchâtel, Switzerland
4Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
5Laboratory Director, Vaunshdhara Fertility Centre, Nagpur, Maharashtra, India
6Discipline of Anatomy and Histology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia
CONFLICTS OF INTEREST
The authors declare no conflicts of interest. SF is also an employee of CooperSurgical Fertility Solutions, but the company had no knowledge of or role in the design, execution, interpretation, or writing of this review article. RS is also an employee of the Vitrolife-Group.†These authors contributed equally to this work.
ABSTRACT
In assisted reproductive technolog, both invasive and non-invasive criteria are widely used to identify oocytes and embryos with high developmental potential, with the ultimate goal of improving live birth rates. Since the earliest applications of in vitro fertilization in the 1970s, non-invasive assessment methods have played a central role in evaluating oocyte and embryo competence. These approaches rely primarily on morphological analysis, in-cluding assessment of the mature cumulus-oocyte com-plex (COC), the presence and morphology of the first polar body, zona pellucida thickness, characteristics of the peri-vitelline space, and cytoplasmic appearance. Oocyte quali-ty is a fundamental determinant of successful fertilization, subsequent embryo development, implantation, and the establishment of a healthy term pregnancy. The follicular environment also plays a crucial role in regulating oocyte maturation and developmental competence. Within the follicle, the COC functions as a coordinated unit in which the oocyte regulates its growth and development through metabolic interactions with the surrounding cumulus and granulosa cells. During maturation, the oocyte’s energy requirements are largely met through the β-oxidation of fatty acids stored in lipid droplets (LDs). These LDs under-go spatial redistribution during maturation, which may be associated with changes in the oocyte’s viscoelastic prop-erties. Alterations in lipid metabolism within the COC can impair oocyte developmental competence and may help explain the reduced survival of some oocytes after intra-cytoplasmic sperm injection. This review critically exam-ines the relationship between the follicular environment and oocyte metabolism, with particular emphasis on lipid metabolism and oocyte and embryo quality. It also dis-cusses established non-invasive markers of oocyte quality and emerging approaches based on oocyte biomechanical properties that may be associated with embryo viability, implantation, and term pregnancy.
Keywords: assisted reproductive technology, non-inva-sive assessment, oocyte morphology, oocyte quality, bio-mechanical properties, lipid metabolism
INTRODUCTION
Over recent decades, assisted reproductive technology (ART) has evolved substantially and has contributed to the birth of approximately 9 million children (De Geyter et al., 2020). Morphological assessment of oocytes remains an important component of routine ART practice. However, oocyte quality is among the most important limiting factors in female fertility and plays a critical role in fertilization and early embryo development (Gilchrist et al., 2008; Mtango et al., 2008). The embryo results from the fusion of an oocyte and a spermatozoon. In vitro fertilization comprises several procedures, among which ovarian stimulation (OS) is one of the most critical (Humaidan et al., 2016). In vivo, usually only one oocyte ovulates each month after a prolonged process of follicular growth and selection. By contrast, OS largely bypasses natural follicular selection and allows the maturation of oocytes from a broader follicular cohort. This process may affect oocyte and embryo quality and may contribute to fertilization failure, embryo aneuploidy, and implantation failure (Mahutte & Arici, 2003; Swain & Pool, 2008).
Successful fertilization is a complex process that depends not only on sperm penetration but also on multiple aspects of oocyte quality. Following OS, a proportion of retrieved oocytes may have suboptimal developmental competence and, despite appropriate culture conditions, may generate embryos with limited implantation potential or an impaired ability to support a term pregnancy (Swain & Pool, 2008; Marteil et al., 2009). Oocyte maturation cannot be determined solely by the presence of the first polar body; it also involves numerous cytoplasmic processes that are not visible by conventional microscopy. These mechanisms and signaling pathways are essential for the synthesis and storage of carbohydrates, lipids, and proteins and for the regulation of metabolic pathways required for oocyte maturation, fertilization, and embryo development. Oocyte quality depends not only on nuclear maturation and the mitochondrial genome but also on the ovarian follicular environment throughout folliculogenesis and during the preovulatory and ovulatory stages (Nagy et al., 2009; Patrizio et al., 2007; Combelles & Racowsky, 2005).
Mammalian embryo development is a highly coordinated molecular and cellular process involving cleavage, embryonic genome activation (EGA), and epigenetic reprogramming. Early embryos primarily use pyruvate and lactate, whereas glucose becomes increasingly important from the morula to the blastocyst stage. Before EGA, metabolism is relatively low and depends on maternal mRNA, proteins, and metabolites accumulated during oocyte maturation. Around and after EGA, energy requirements increase because of rapid cell proliferation, differentiation, blastocoel formation, and hatching; these requirements also differ between the inner cell mass and trophectoderm (Lipinska et al., 2023; Bradley et al., 2016; Bradley & Swann, 2019).
Lipid uptake and storage are key components of energy metabolism in both oocytes and embryos (Sudano et al., 2011; Lipinska et al., 2023). Intracellular lipids are stored mainly as triacylglycerols and sterol esters within specialized organelles known as lipid droplets (LDs). Following hydrolysis, fatty acids can be mobilized from LDs to mitochondria, where they serve as substrates for β-oxidation. Lipid droplets are dynamic structures that can change in size, abundance, and cytoplasmic distribution. Their morphology also changes during embryo development to accommodate lipid storage and interactions with other organelles (Sudano et al., 2016). Lipid droplet distribution may reflect the metabolic state of the oocyte or embryo: dispersed LDs are associated with more active β-oxidation, whereas LD fusion is associated with increased glycolytic activity (Bradley & Swann, 2019). This review therefore examines the characteristics of LDs in mammalian oocytes, their relationship with developmental competence, and their potential association with embryo competence and live birth.
Search strategy
This narrative review provides a comprehensive overview of the literature on oocyte metabolism, with particular emphasis on LDs. Mammalian embryo development is regulated by a complex network of metabolic pathways, among which energy metabolism plays a central role in developmental competence. The ability of the oocyte to accumulate, store, and use lipids during oogenesis and throughout preimplantation development may be essential for embryonic growth, implantation, and successful pregnancy. Lipid droplets function as intracellular energy reservoirs and contribute to membrane synthesis, cellular signaling, and protection against metabolic stress. Variations in lipid content and distribution within oocytes and early embryos may therefore influence developmental potential and reproductive outcomes. Increasing evidence indicates that disturbances in lipid metabolism are associated with changes in embryo quality, implantation, and live birth. Relevant studies were identified through a structured search of the English-language literature in PubMed. Search terms reflected the scope of the review and included combinations related to oocyte metabolism, LDs, lipid content, embryo development, pregnancy outcomes, and live birth. Studies involving both animal models and humans were considered to provide a broad translational perspective. Publications available up to September 2025 were reviewed, critically evaluated, and synthesized.
Biomechanical properties of the oocyte
Recently, the biomechanical properties of cells and their association with function, health, and cell evolution have been studied by several authors. Viscoelasticity indicates the property of materials to display elastic and viscous features when undergoing deformation. Cell membranes are an example of a viscoelastic material (Evans & Hochmuth, 1976; Dimitrov, 1984), and intracellular cytoskeletal constitution and remodelling have important relationships to a cell’s viscoelastic nature (Berteau et al., 2016). Also lipids, in the form of saturated and unsaturated fatty acids (FAs), can alter the delicate metabolic balance necessary for the embryo to thrive (Gomez et al., 2021; Cortezzi et al., 2013; Haggarty et al., 2006). Lipids and FAs are critical for several biochemical processes required for embryo development, and are involved in the arrangement of cellular phospholipid membranes for structural integrity in the provision of energy reserves for survival until successful implantation (Brusentsev et al., 2019; Lipinska et al., 2023; Bradley et al., 2016; Bradley & Swann, 2019). Several studies have demonstrated that interactive biophysical forces, such as cell/membrane deformation and fluid-flow shear stresses, affect cellular viscoelasticity (Karcher et al., 2003; Sato et al., 1996; Shôji et al., 1978). In cancers, as well as in stem cells, viscoelasticity has been shown to influence cell structure, function, and biophysical properties (Xu et al., 2012; Engler et al., 2006).Reproductive studies have currently proposed that assessment of oocyte biomechanical properties may contribute insight into oocyte and subsequent embryo development. The cytoplasmic viscosity (CV) of the oocyte has been the subject of investigation by a few authors, who have proposed that both viscosity and resistance have a significant effect on embryo development, in particular on fertilization, embryo quality, and blastocyst formation (Ebner et al., 2003). Further, it has been illustrated that during follicle maturation in OS regimes, the CV may undergo substantial changes, going from more aqueous to more viscous and stickier. Generally, these novel findings suggested that higher viscosity might be an unfavorable prognostic indicator of embryo development and pregnancy outcomes (Ebner et al., 2003). Differences in CV have also been reported according to patients’ cause of infertility and with different OS protocols (Ebner et al., 2003; 2010). The CV of the mature oocyte and membrane resistance may be an important aspect to consider, and perhaps future studies will explain why some oocyte membranes break immediately during intracytoplasmic sperm injection (ICSI) (and sometimes display degeneration soon after the injection), while others fail to break even with aspiration (Dumoulin et al., 2001; Yanez et al., 2016).Therefore, additional relevant investigation should be performed on the zona pellucida (ZP), which is an oocyte-associated structure, and is a sulphated glycoprotein matrix that is shaped enclosing the primary oocyte during early stages of folliculogenesis in mammals (Rankin et al., 2000). The human ZP is formed by four glycoproteins (Lefièvre et al., 2004; Gupta et al., 2012), and plays a crucial role during fertilization, during binding of the spermatozoa to the oocyte. It stimulates the acrosome reaction in the head of the spermatozoon (Ganguly et al., 2010) and soon after sperm binding and passage through the ZP, the structure of the ZP changes to prevent polyspermy (Wolf, 1981; Wassarman, 1999). Using atomic force spectroscopy, Papi et al. (2010) demonstrated that the ZP of immature bovine oocytes exhibits predominantly elastic behaviour, whereas in mature and fertilized oocytes the ZP becomes progressively more plastic, requiring greater force to induce deformation. However, it has been well known that after fertilization, the fusion of oocyte cortical granules with the oolemma and discharge of their enzymatic contents into the perivitelline space results in ZP “hardening” and represents an important mechanism to reduce the incidence of polyspermy (Bedford & Cross, 1978; Drobnis et al., 1988).A compelling study by Yanez et al. (2016) conducted viscoelastic testing on mouse and human zygotes. Using a narrow micropipette aspiration platform that allowed quantification of depth of aspiration of the ZP, and part of the cell membrane, the authors measured and quantified four biomechanical features of a linear elastic solid model for each zygote investigated (Yanez et al., 2016). Ebner et al. (2003) examined CV in human oocytes at the time of sperm injection and investigated whether persistence of the injection funnel during ICSI affected embryo development and clinical outcomes. Although oocytes with a persistent funnel showed less degeneration after injection, they were associated with poorer zygote quality, a higher proportion of poor-quality embryos, fewer good-quality blastocysts, and lower clinical pregnancy rates. Overall, increased CV delayed early embryonic development and impaired embryo quality, making injection funnel persistence a negative prognostic marker for preimplantation development (Ebner et al., 2003). Although these findings are encouraging and highlight the potential of non-invasive oocyte assessments, adequately powered prospective randomized controlled studies in humans are required to determine whether viscoelastic measurements can reliably predict developmental competence and pregnancy outcomes (Yanez et al., 2016; Papi et al., 2010; Kort & Behr, 2017; Ebner et al., 2003).
ATP production and energy metabolism in the cu-mulus-oocyte complex
Metabolic reactions within living cells sustain their existence by creating adenosine triphosphate (ATP), a source of energy. ATP is essential for protein synthesis, homeostasis, and cellular activities during growth and development. It is often used as a diagnostic marker of cell viability. An increase in ATP synthesis corresponds to a higher energy demand for the cell. Oocyte quality is significantly affected by the growth and maturation environment, with healthy energy metabolism playing a crucial role in nuclear and cytoplasmic maturation and embryo developmental competence (Warzych & Lipinska, 2020). Oocyte quality is crucial for mammalian reproduction, influencing embryo development and implantation potential. It is influenced by maturation features, the environment, chemical compounds, and genetic variables. Indeed, nutritive cumulus cells (CCs) encircle a developing oocyte within the follicle, supplying it with ATP and metabolic substrates, including pyruvate, a byproduct of glycolysis. Maternal nutritional and health status is reflected in the composition of her follicular fluid (FF) and, consequently, the oocyte itself (Bradley & Swann, 2019).
Energy substrates used by oocytes and embryos
Carbohydrates
Whether oocytes can directly absorb glucose remains uncertain (Clark et al., 2011). Multiple studies have shown that CCs play a dominant role in glycolysis-dependent metabolism of exogenous glucose products that are delivered to the oocyte through gap junctions (Sugiura et al., 2005; Sutton-McDowall et al., 2010). Within the cumulus-oocyte complexes (COCs), glucose is metabolized through the hexosamine biosynthetic pathway to support the synthesis of hyaluronan, a key component required for the development, expansion, and structural integrity of the cumulus extracellular matrix (Sutton et al., 2003). Live fluorescence imaging studies examining glucose uptake in mouse COCs have demonstrated that glucose enters CCs through facilitative glucose transporters (GLUTs) and is then transferred to the enclosed oocyte via intercellular gap junctions (Wang et al., 2012). Since the oocyte itself has a limited ability to metabolize glucose efficiently, most glycolytic processing occurs within the surrounding CCs, highlighting their essential metabolic support role during oocyte development and maturation (Sutton-McDowall et al., 2004). Denuded bovine oocytes have low phosphofructokinase activity, while the CCs of COCs show relatively high levels of this activity (Cetica et al., 2002). Additionally, CC depleted mouse oocytes had lower glucose absorption than COCs. The inhibition of GLUTs reduced glucose absorption in COCs and CCs but did not affect denuded oocytes (Wang et al., 2012), demonstrating the variations in the glucose transport routes between oocytes and COCs. Denuded pig oocytes cultured in the presence of 2.78 mM glucose showed higher rates of nuclear maturation compared to oocytes in vitro matured in the absence of glucose (Tsuzuki et al., 2008). Denuded pig oocytes may sustain nuclear maturation using glucose, which is possibly species-specific, and glycolysis and the pentose phosphate pathway are crucial for the reinitiation of meiosis (Wang et al., 2012; Cetica et al., 2002).
Pyruvate metabolism
Most mammalian species use pyruvate, a crucial metabolic substrate produced by CCs during the formation of oocytes within follicles, despite variations in substrates used for oocyte metabolism (Dumollard et al., 2008). Increased use by the tricarboxylic acid (TCA), or Krebs’, cycle of pyruvate, glutamine, and glycine suggests that oxidative metabolism is crucial for supplying energy during oocyte maturation (Shi & Sirard, 2022). Pyruvate oxidation is a major source of ATP for early-cleavage-stage embryos and human and mouse oocytes (Sturmey & Leese, 2003). Oocytes absorb pyruvate and lactate from the surrounding media or FF, which are transported to mitochondria by the pyruvate dehydrogenase (PDH) complex, where they are oxidized to acetyl CoA. Acetyl-CoA then joins the chemical processes of the TCA cycle, reducing the co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide. The electron transport chain (ETC) involves the transfer of electrons to membrane-bound proteins, which convert O2 into H2O, thereby driving the synthesis of ATP. Overoxidation of pyruvate can result in a partial reduction of O2 to superoxide and electron leakage from the ETC, both of which produce harmful reactive oxygen species (ROS). Although lactate and lactate-derived pyruvate are not absorbed by mitochondria for the synthesis of ATP, they contribute to redox equilibrium by generating NADH. Glutathione is a crucial antioxidant that can be reduced by cytosolic nicotinamide adenine dinucleotide phosphate (Bradley & Swann, 2019).
Fatty acids
A FA represents a highly efficient form of energy storage, with complete oxidation of palmitate yielding approximately 106 ATP molecules, compared with around 30 ATP molecules produced from glucose oxidation (Fu et al., 2021). This high energy density makes FAs particularly important in cell types with substantial energy demands. Endogenous lipids are therefore thought to play a key role in oocyte maturation, with oocytes likely relying on these substrates as a primary energy source during in vitro maturation (IVM) (Zeilmaker & Verhamme, 1974). Within the cell, lipids are predominantly stored as triglycerides in cytoplasmic LDs, which serve as dynamic reservoirs that can be mobilized according to metabolic requirements. During oocyte maturation, triglyceride levels within the ooplasm decrease, coinciding with an increase in oxygen consumption, suggesting enhanced mitochondrial β-oxidation and oxidative phosphorylation (Sturmey & Leese, 2003). Functional studies support the importance of this pathway, as inhibition of β-oxidation during porcine oocyte maturation disrupts nuclear maturation, early cleavage, and subsequent blastocyst formation (Sturmey et al., 2006). Similarly, chemical modulation of FA oxidation (FAO) has demonstrated that this metabolic process is essential for successful oocyte maturation across multiple species, including mice (Dunning et al., 2011). Fatty acid metabolism in the oocyte is tightly linked to insulin signalling, which regulates lipid uptake, storage, and oxidation through pathways involving phosphoinositide 3-kinase and protein kinase B. Disruption of insulin signalling, as occurs in insulin resistance or metabolic disease, may impair FAO by altering mitochondrial substrate availability and enzyme activity. Excessive intracellular lipid accumulation under such conditions can promote lipotoxicity, leading to increased production of ROS (Dunning et al., 2011; Sturmey et al., 2006). Elevated ROS generation contributes to oxidative stress, which can damage mitochondrial DNA, proteins, and membranes, ultimately impairing ATP production. Mitochondrial dysfunction further compromises FAO efficiency, creating a vicious cycle of reduced energy output and increased oxidative damage. In parallel, lipid overload and oxidative stress can induce endoplasmic reticulum (ER) stress, activating the unfolded protein response. Persistent ER stress may disrupt calcium homeostasis and interfere with protein folding, processes that are critical for oocyte maturation and developmental competence. Together, these interconnected pathways highlight the central role of FA metabolism in supporting oocyte energy demands while underscoring the vulnerability of this system to metabolic imbalance. Proper regulation of insulin signalling, mitochondrial function, and cellular stress responses appears essential for maintaining oocyte quality and successful developmental outcomes.
Lipids
Lipids are essential for nutrition, hormone synthesis, signalling, cell-to-cell interactions, and membrane building, as well as crucial for cellular function. Lipids are also a significant energy source and may be the primary substrate within the oocytes of porcine and bovine species (Shi & Sirard, 2022; Sturmey & Leese, 2003). For mammalian oocytes and early cleavage- stage embryos to progress from ovulation to the compacted morula stage, approximately 100,000 mitochondria present within cells aid in producing ATP. For the synthesis of ATP, they almost exclusively use oxidative phosphorylation of intracellular substrates such as pyruvate, FAs, and glutamine (Bradley & Swann, 2019). Oocytes and CCs contain lipases, which are responsible for triglyceride metabolism. Optimized lipid metabolism in oocytes and surrounding CCs enhances oocyte quality and embryonic development (Dunning et al., 2014). For energy production, FAs from LDs are converted to acetyl-CoA; this process is known as β-oxidation (Li et al., 2023; Dunning et al., 2010). The luteinizing hormone surge triggers β-oxidation in COCs to resume and complete nuclear maturation to the metaphase II (MII) stage, preparing for fertilization (Dunning et al., 2014). The complex relationship that exists between reproductive outcomes and metabolic processes has become an important area of investigation for reproductive scientists (Leese, 2015). The metabolic environment plays a critical role in the development of mammalian oocytes and embryos, with lipid metabolism receiving special attention. Understanding the metabolic profile during critical phases is crucial for comprehending embryo quality, development, viability, and pregnancy outcomess (Dumesic et al., 2015). Lipid metabolites function as meiotic resumption regulators and precursors of steroid hormone synthesis, including lipoproteins, cholesterol, and 14- dimethyl-14- dehydrolanosterol (Follicular Fluid Meiosis Activating Sterol). Long-term fat exposure can damage follicles and disrupt oocyte meiosis, as insulin, cortisol, and gonadotropins control lipid homeostasis within follicles (Liu et al., 2022). Lipids are crucial for energy storage and plasma membrane production in embryonic development, but excessive LD formation can disrupt mitochondrial activity and lipid metabolism (de Andrade Melo-Sterza & Poehland, 2021).
Metabolic dynamics during oocyte maturation
Oocyte maturation involves dynamic metabolic processes, including energy metabolism for biosynthesis, requiring oxidative phosphorylation, glycolysis, and the TCA cycle to maintain a delicate equilibrium. Recent research highlights the crucial role of lipid metabolism in maintaining energy supplies during maturation, particularly FAO, and suggests active regulation of processes related to lipid metabolism is likely necessary to preserve energy homeostasis in CCs and encourage the completion of oocyte maturation (Sanchez-Lazo et al., 2014). During high-fat circumstances, such as obesity or under a high-fat maternal diet, free fatty acids (FFAs) persist in the cytosol, and excess FFAs have the potential to undergo lipid peroxidation and produce ROS. Additionally, FFAs may directly impact calcium (Ca2+) storage within the ER, resulting in ER stress and increasing intracellular Ca2+ levels. When Ca2+ reaches the mitochondria, PDH activity rises, increasing the generation of ROS (Bradley & Swann, 2019).
Fatty acid composition of lipid droplets in oocytes
Saturated versus unsaturated FAs, have distinct effects on the developmental competence and maturity of oocytes. By providing oocytes and embryos with the right energy substrates and vital co-factors, it is possible to optimize their development in vitro. Likewise, more research is necessary to determine how physiological factors, such as food, affect access to FAs by COCs in vivo (Dunning et al., 2014). Analysis of the FA composition of mammalian oocytes by several authors reveals that saturated FAs, which are composed of a simple acyl chain without a carbon-carbon double bond, make up the largest proportion of lipids in most mammalian oocytes. Most of them are made up of stearic (18:0) and palmitic (16:0) acids (Sanchez-Lazo et al., 2014; McEvoy et al., 2000; Haggarty et al., 2006). About 30% and 15% of total FAs are composed of polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs), respectively. Oleic acid (OA) (18:1 n-9) is always the most prevalent MUFA, while the main components of the PUFA component are arachidonic acid (20:4 n-6) and linoleic acid (LA) (18:2 n-6) (McEvoy et al., 2000; Haggarty et al., 2006). Notably, PUFAs, which mostly comprise LA, make up more than twice as many of the total FAs in pig oocytes compared to ruminant oocytes (McEvoy et al., 2000). There is a suggestion that oocytes with low amounts of PUFA due to oxidative damage may not be viable (Tarín, 1996). According to the study by Matorras et al. (1998), saturated FAs made up 79.22% of the total FAs, with stearic (38.65%) and palmitic (32.66%) acids being the most prevalent. With 14.27% of all MUFA, OA was the most prevalent at 9.77%. The proportion of docosahexaenoic acid to eicosapentaenoic acid (EPA) was around five-fold.The most prevalent FAs in human unfertilized oocytes are saturated or MUFAs, which serve as energy sources, with variations in their content compared to other biological specimens. Particularly, OA and LA were less predominant with stearic and EPAs more prominent; this may be due to a unique characteristic of oocyte metabolism (Matorras et al., 1998). A better understanding of the in vivo control of lipid levels, lipid metabolism, and vital co-factors, methods for enhancing domestic animal oocyte development potential and reducing female subfertility may be developed. When compared to glucose, FAs exhibit a 5- to 6-fold increase in ATP production due to their high energy value (Bertevello et al., 2018). There are 37 FAs in horse FF, with a total concentration of 600µg/ml. The compounds with the greatest concentrations include stearic acid (SA) (31µg/ml), palmitic acid (PA) (26µg/ml), LA (48µg/ml), and OA (87µg/ml) (Bender et al., 2010). The overall quantity of FAs in the FF of prepubertal girls is 890µg/ml. Among these, PA (232µg/ml), OA (203µg/ml), LA (190µg/ml), and SA (142µg/ml) are the most prevalent specific FAs. Many factors influence the content of certain FAs, such as the reproductive state of females (Bender et al., 2010; Pawlak et al., 2012). FA levels vary based on nutritional conditions, and females with metabolic issues often have elevated levels, particularly non-esterified FAs, which can harm granulosa cell (GC) development, as well as oocyte and embryo quality (Shi & Sirard, 2022). The oocyte receives energy and chemical signals from GCs, including CCs, through a substance exchange network, with each COC enhancing embryonic growth (Zhang et al., 2023).
Lipid Droplets in Oocytes and Early Embryos
Mammalian oocytes have endogenous stores of FAs in the form of LDs, which enter the developing oocyte and their nutritive CCs. Most FAs are esterified to glycerol molecules and stored as neutral triacylglycerols (TAGs) in hydrophobic lipid vesicles. LDs, a phospholipid monolayer-coated neutral lipid core, are essential for cell lipid metabolism and are found in mammalian oocytes and embryos, but their physiological roles are not fully understood (Aizawa et al., 2019). LDs are formed within the ER, composed of a neutral TAG core and a single phospholipid layer, often with various protein inclusions (Fujimoto & Parton, 2011; Walther & Farese, 2012; Pratt & George, 1989). Lipids also play a part in membrane maintenance, undoubtedly vital for the large increase in plasma membrane surface area observed in cleaving embryos; a 74% increase in plasma membrane surface area between the 2-cell and 4-cell embryo stages, indicating a larger increase in later preimplantation stages (Pratt & George, 1989). During subsequent embryonic development from the early cleavage stage to the blastocyst stage, a discernible drop in lipid content is observed (Romek et al., 2009). Droplets are broken down by lipases at the LD surface, releasing FAs for mitochondrial metabolism. Post-fertilization, lipophagy induces selective autophagy of LDs by lysosomes (Tsukamoto et al., 2008). According to Bradley et al. (2016) there are significant changes in LD aggregation levels during oocyte maturation and embryo preimplantation development, suggesting it could predict developmental potential. LDs in germinal vesicle oocytes are uniformly distributed throughout the cell’s cytoplasm, whereas in MII oocytes, there are more clusters and fewer scattered droplets. Notably, at the morula and blastocyst stages, larger LDs appear. At the same time, there is a shift in ATP and pyruvate supply towards glycolysis, possibly indicating decreased β-oxidation and FA storage (Bradley et al., 2016).According to the study by Li and colleagues (2023), which analysed the function of LDs in the reproductive system, the authors concluded that LDs perform various functions such as energy metabolism, lipid membrane conversion, signalling, stress reduction, temporary storage of proteins, and prevention of bacterial infection (Li et al., 2023). FAs may also be oxidized, which releases energy and yields carbon dioxide and H2O as byproducts. LDs are essential for preserving the equilibrium of energy metabolism. When under nutritional stress, cells mobilize FAs through two major pathways. Maternal nutritional excess can cause placental abnormalities, foetal exposure to toxic chemicals, and immune system interference, leading to obesity-related inflammation and increased oxidative stress and lipotoxicity (Rao et al., 2020). However, the anti-stress properties of LDs maintain normal cellular function by stabilizing the cellular environment and drastically lowering the risk of cellular lipotoxicity. Embryo development is adversely affected by bacterial infection. In addition to providing energy for embryonic growth through lipophagy and interconversion with glycogen in embryonic cells, the membrane components of LDs also serve as membrane precursors for syncytium division. LDs prevent excess histone breakdown, and strengthen resistance to bacterial invasion by temporarily retaining nutrients and proteins from the mother (Anand et al., 2012). LDs provide membrane precursors for blastocyst cellularization, and their influence on membrane components during cell differentiation is significant (Chen et al., 2014). Defects and embryonic developmental arrest are observed when LDs are removed from fertilized eggs or early embryos (Li et al., 2023). Understanding the interaction between lipids and other nutrients, such as proteins, is crucial for comprehending the biological complexities of embryonic development. Research on embryonic cellularization, including LD-derived membrane precursors and protein storage, is crucial.
Concluding remarks
The follicular environment regulates oocyte maturation and developmental competence. Within the follicle, the COC functions as a coordinated unit in which the oocyte regulates its growth and maturation through metabolic interactions with the surrounding cumulus and GCs. The energy requirements of the oocyte during maturation are met largely through the β-oxidation of FAs stored in LDs. Redistribution of LDs occurs during maturation and may be related to changes in the oocyte’s viscoelastic properties. Disruption of lipid metabolism within the COC may reduce the viability of mature oocytes and may help explain why some oocytes do not survive ICSI. In addition, altered energy metabolism and excessive lipid accumulation in oocytes and embryos may result from maternal obesity or an unbalanced diet. Oocytes and embryos are particularly sensitive to changes in their microenvironment. A better understanding of the metabolic regulation of oocyte maturation and embryogenesis may support improvements in IVM media and the development of more individualized embryo culture systems.
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