Characterizing the follicular fluid metabolome: quantifying the correlation across follicles and differences with the serum metabolome

Hood, Robert B.; Liang, Donghai; Tan, Youran; Ford, Jennifer B.; Souter, Irene; Jones, Dean P.; Hauser, Russ; Gaskins, Audrey J.

doi:10.1016/j.fertnstert.2022.07.023

Cited by 14 publications

(4 citation statements)

References 50 publications

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“…There was a certain correlation between metabolism in serum and FF in patients undergoing IVF treatment. Given that FF is less disrupted by other tissues and organs than serum, and in predicting embryo quality and developmental competence, changes in FF cytokines are more reliable than those in serum [ 29 ]. Therefore, we tried to identify a potential biomarker associated with embryo quality in PCOS patients with a normal BMI undergoing IVF treatment.…”

Section: Discussionmentioning

confidence: 99%

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment

Shang,

Wang,

Wang

et al. 2024

Reprod Biol Endocrinol

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Background Polycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility in women of reproductive age, and low-grade chronic inflammation plays a key role in the occurrence and development of PCOS. However, obesity, as a likely confounding factor, can affect the inflammatory state of PCOS patients. Objective The aim of this study was to comprehensively investigate intra-ovarian inflammatory states and their impact on embryo quality in PCOS patients with a normal BMI undergoing IVF treatment. Methods DIA-mass spectrometry-based proteomics and bioinformatic analysis were combined to comprehensively profile the protein expression of granulosa cells (GCs) from 5 normal-BMI PCOS patients and 5 controls. Thirty-four cytokines were further systematically detected in follicular fluid (FF) from 32 age- and BMI-matched normal-BMI patients using Luminex liquid chip suspension technology. Next, the differentially expressed cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA) in 24 newly recruited subjects, and the relationship between these cytokines and embryo quality in PCOS patients was analysed. Finally, these cytokine levels were compared and evaluated in PCOS patients with different androgen levels. Results Proteomic analysis showed that the suppression of substance metabolism and steroid biosynthesis, more interestingly, resulted in an enhanced immune and inflammatory response in the GCs of normal-BMI PCOS patients and prompted the involvement of cytokines in this process. Luminex analysis further showed that FF macrophage inflammatory protein-1 beta (MIP-1β) and stromal cell-derived factor-1 alpha (SDF-1α) levels were significantly increased in normal-BMI PCOS patients compared to controls (P = 0.005; P = 0.035, respectively), and the ELISA results were consistent with these findings. Besides, FF MIP-1β showed an inverse correlation with the number of D3 good-quality embryos and the good-quality blastocyst rate in patients with PCOS (P = 0.006; P = 0.003, respectively), which remained significant after correction for multiple comparisons. Moreover, SDF-1α levels had no relationship with embryo development in PCOS patients. Additionally, SDF-1α levels were significantly lower in PCOS patients with high androgen levels than in controls (P = 0.031). Conclusions Local ovarian inflammation was present in normal-BMI PCOS patients, affecting follicular development, and FF MIP-1β may be a potential biomarker associated with embryo quality in normal-BMI PCOS patients. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment

Shang,

Wang,

Wang

et al. 2024

Reprod Biol Endocrinol

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“…When considering the differences between CFF and pooled IF, we found that FF of infertile females had bilirubin concentrations (free, conjugated and total) 2–3 times higher than those measured in FF of fertile females. Since the concentrations of the majority of the low-molecular-weight compounds detectable in FF reflect, under physiological conditions, those found in serum [ 32 ], we hypothesized that IF may have high levels of circulating bilirubin, thus explaining the higher concentrations in their FF, compared to those in FF of CFF. The retrospective analysis allowed the recovery of a limited number of FF donors who performed routine blood analysis (in the days before pickup) that also included the determination of serum bilirubin.…”

Section: Discussionmentioning

confidence: 99%

Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization

Mangione

Pallisco²,

Bilotta³

et al. 2023

IJMS

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In a previous study, we showed that various low-molecular-weight compounds in follicular fluid (FF) samples of control fertile females (CFF) have different concentrations compared to those found in FF of infertile females (IF), before and after their categorization into different subgroups, according to their clinical diagnosis of infertility. Using the same FF samples of this previous study, we here analyzed the FF concentrations of free and bound bilirubin and compared the results obtained in CFF, IF and the different subgroups of IF (endometriosis, EM, polycystic ovary syndrome, PCOS, age-related reduced ovarian reserve, AR-ROR, reduced ovarian reserve, ROR, genetic infertility, GI and unexplained infertility, UI). The results clearly indicated that CFF had lower values of free, bound and total bilirubin compared to the respective values measured in pooled IF. These differences were observed even when IF were categorized into EM, PCOS, AR-ROR, ROR, GI and UI, with EM and PCOS showing the highest values of free, bound and total bilirubin among the six subgroups. Using previous results of ascorbic acid, GSH and nitrite + nitrate measured in the same FF samples of the same FF donors, we found that total bilirubin in FF increased as a function of decreased values of ascorbic acid and GSH, and increased concentrations of nitrite + nitrate. The values of total bilirubin negatively correlated with the clinical parameters of fertilization procedures (number of retrieved oocytes, mature oocytes, fertilized oocytes, blastocysts, high-quality blastocysts) and with clinical pregnancies and birth rates. Bilirubin concentrations in FF were not linked to those found in serum samples of FF donors, thereby strongly suggesting that its over production was due to higher activity of heme oxygenase-1 (HO-1), the key enzyme responsible for bilirubin formation, in granulosa cells, or cumulus cells or oocytes of IF and ultimately leading to bilirubin accumulation in FF. Since increased activity of HO-1 is one of the main enzymatic intracellular mechanisms of defense towards external insults (oxidative/nitrosative stress, inflammation), and since we found correlations among bilirubin and oxidative/nitrosative stress in these FF samples, it may reasonably be supposed that bilirubin increase in FF of IF is the result of protracted exposures to the aforementioned insults evidently playing relevant roles in female infertility.

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“…Therefore, the results of our study have to be interpreted with caution. However, it is impractical to measure steroids from all follicles in clinical routine, and a large overlap and strong correlation was observed between metabolomic features across follicles within a woman [ 42 ]. Therefore, the results of the first aspirated ovarian follicle may give us a hint.…”

Section: Discussionmentioning

confidence: 99%

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

Yang

Pan

Zhou

et al. 2023

Heliyon

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Characterizing the follicular fluid metabolome: quantifying the correlation across follicles and differences with the serum metabolome

Cited by 14 publications

References 50 publications

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment

Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

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