Table 1 Components in follicular fluid and their physiological roles
Composition | Chemical nature | Secretory cycle | Involved pathway | Role | Affecting factor |
|---|---|---|---|---|---|
Extracellular vesicle | membrane-bound particles | - | Wnt, TGFβ, MAPK, ErbB, and ubiquitin-mediated pathways.Ptgs2,Ptx3 and Tnfaip6 expression. | EVs are transporters for proteins and other regulatory molecules such as microRNAs (miRNAs), proteins, and lipids. | Age |
GnRH | including FSH, hCG, and LH | - | FSH stimulates cAMP/PKA, MAPK/ERK, and PI3K/Akt pathway.LH activates the IGF system and cAMP pathways | GnRH stimulates sterogenesis, proliferation of GC, and oocyte meiosis resumption., inhibit apoptosis of GCs. | |
Steroid hormone | estrogen, progesterone and androgen | Before ovulation, the FF E2 reaches a significant peak. | E2 induces FSHR, LHR, aromatase, and IGF1 expression, inflammatory pathway | E2 enhances GC proliferation and HPSC, inhibits subordinate follicle and GC apoptosis. P induces granulosa cell luteinization and oocyte maturation. androgen promotes early follicle recruitment and growth but inhibits later follicle maturation and ovulation. | Age and ovarian reserve. |
Melatonin | an antioxidant | Melatonin levels show a 24-hour rhythm in the follicles. | Melatonin activates the Sirt1/Sod2 pathway and PI3K/AKT signaling pathway, enhance GADD45,eIF2 and ARF signaling and VEGF expression. | Melatonin serves as a receptor-independent free radical scavenger directly and enhances antioxidant enzyme activity indirectly to reduce ovarian oxidative stress and mediate sterogenesis. | Age |
AMH | glycoprotein dimer in the transforming growth factor superfamily | FF AMH decreases as follicles enlarge, with a significant decline observed at 8–10 mm. | AMH inhibits CYP19, P450scc and LHR expression | AMH inhibits sterogenesis and dominant follicular selection. Its role in ovarian reserve, follicular development, and oocyte maturity rate is controversial. | Age |
Inhibin and activin | dimeric glycoproteins belonging to the transforming growth factor beta superfamily | Inhibin A and activin A are actively produced throughout follicular growth Inhibin B is not to be actively produced. | All the Activin isoforms target ALK4-mediated SMAD2/SMAD4-dependent pathway. Activin A suppresses JNK, ERβ-mediated autophagy signaling. Inhibin B mediates paracrine and endocrine pathways. inhibin A mediates the Mt-mediated pathway and promotes CNA and CyclinB1. | Inhibin and activin regulate FSH and steroid hormone production, inhibit GCS apoptosis. Inhibin activates dominant follicle selection and oocyte meiosis. | |
BMP15 and GDF9 | TGF-β superfamily as oocyte secretion factors(OSF) | highest FF BMP15 and GFF9 before follicle selection. | GDF9/BMP15 heterodimer activates Smad2/3 signaling. BMP15 induce KITL, GDF-9 promote Has2、Tnfip6、Ptx3 and Ptgs2 expression. | GDF9 and BMP15 play important roles in follicular development including pre-antral follicle recruitment, cumulus expansion, oocyte maturation, and ovulation through modulation of Intrafollicular paracrine signaling between GCs and oocytes. | Age-related decline. |
VEGF | angiogenic factors | FF VEGF increases as follicles enlarge, and peaks before ovulation | VEGF participates in the VEGF-VEGFR-2 pathway, being induced via SMAD2/3, ERK1/2, p38 MAPK, and PI3K/AKT signaling pathway. | VEGF induces ovarian angiogenesis, facilitates the provision of oxygen, gonadotropins, and nutrients to the follicles, ultimately leading to the activation of primordial follicles. | Age and FSH levels |
ROS | O2-, H2O2, OH-, O3, 1O2 | FF ROS is maintained in the itesitseostatic range by the maturing and ovulated oocyte. | H2O2- cAMP-CDK1,GH-ROSpathway | The physiological level is beneficial during folliculogenesis, oocyte maturation, and embryogenesis. Overgeneration of ROS results in a decline in oocyte quality. | Age |
Lipid | phospholipid triglyceride free fatty acid | Throughout follicular development | accumulation of lipid induces ER stress pathways. LPCs mediate phospholipase A2 activation via caspase 3 .S1P induces pCREB-FOXO1/EREG.LPS can alter CEBP signaling. | Lipids serve as energy sources for oocyte growth and development and participate in GC survival and apoptosis. Lipid buildup impaired oocyte maturation. | BMI and age |