Protein pathways working in human follicular fluid: the future for tailored IVF?

The human follicular fluid (HFF) contains molecules and proteins that may affect follicle growth, oocyte maturation and competence acquiring. Despite the numerous studies, an integrated broad overview on biomolecular and patho/physiological processes that are proved or supposed to take place in HFF during folliculogenesis and oocyte development is still missing. In this review we report, for the first time, all the proteins unambiguously detected in HFF and, applying DAVID (Database for Annotation, Visualization and Integrated Discovery) and MetaCore bioinformatic resources, we shed new lights on their functional correlation, delineating protein patterns and pathways with reasonable potentialities for oocyte quality estimation in in vitro fertilisation (IVF) programs. Performing a rigorous PubMed search, we redacted a list of 617 unique proteins unambiguously-annotated as HFF components. Their functional processing suggested the occurrence in HFF of a tight and highly dynamic functional-network, which is balanced by specific effectors, primarily involved in extracellular matrix degradation and remodelling, inflammation and coagulation. Metalloproteinases, thrombin and vitamin-D-receptor/retinoid-X-receptor-alpha resulted as the main key factors in the nets and their differential activity may be indicative of ovarian health and oocyte quality. Despite future accurate clinical investigations are absolutely needed, the present analysis may provide a starting point for more accurate oocyte quality estimation and for defining personalised therapies in reproductive medicine.

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The expression of matrix metalloproteinase-9 in human follicular fluid is associated with in vitro fertilisation pregnancy

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.2005.00574.x ◽

2005 ◽

Vol 112 (7) ◽

pp. 946-951 ◽

Cited By ~ 19

Author(s):

Dong-Mok Lee ◽

Tae-Kyun Lee ◽

Hai-Bum Song ◽

Cheorl-Ho Kim

Keyword(s):

Matrix Metalloproteinase ◽

Follicular Fluid ◽

Matrix Metalloproteinase 9 ◽

In Vitro Fertilisation ◽

Human Follicular Fluid ◽

Metalloproteinase 9

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Antioxidant activities and lipid peroxidation status in human follicular fluid: age-dependent change

Zygote ◽

10.1017/s0967199421000241 ◽

2021 ◽

pp. 1-5

Author(s):

H. Debbarh ◽

N. Louanjli ◽

S. Aboulmaouahib ◽

M. Jamil ◽

L. Ahbbas ◽

...

Keyword(s):

Lipid Peroxidation ◽

Follicular Fluid ◽

Maternal Age ◽

Antioxidant Activities ◽

Human Follicular Fluid ◽

Age Related ◽

Group I ◽

Group Ii ◽

Scavenging Efficiency

Summary Maternal age is a significant factor influencing in vitro fertilization (IVF) outcomes. Oxidative stress (OS) is one of the major causes of age-related cellular and molecular damage. The purpose of this work was to investigate the correlation between maternal age with intrafollicular antioxidants and OS markers in follicular fluid (FF), and also to determine the OS status in patients of advanced age. This study was a prospective study including 201 women undergoing IVF whose age was between 24 and 45 years old. FF samples were obtained from mature follicles at the time of oocyte retrieval. After treatment of FF, lipid peroxidation levels (MDA) and enzyme activities such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione (GSH) level were evaluated using spectrophotometry. The results indicated that the age cutoff point for increasing the MDA level was fixed at 37 years, allowing the study to be differentiated into two age groups. Group I included patients whose age was less than 37 years, and group II included patients whose age was greater than or equal 37 years. Statistical analysis revealed that MDA and GSH levels and GR activity were significantly higher in group II compared with group I. The SOD and CAT activities were significantly less in group II compared with group I. We concluded that from 37 years old a reproductive ageing was accompanied by a change in the antioxidant pattern in FF that impaired reactive oxygen species scavenging efficiency.

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Mitochondrial enrichment in infertile patients: a review of different mitochondrial replacement therapies

Therapeutic Advances in Reproductive Health ◽

10.1177/26334941211023544 ◽

2021 ◽

Vol 15 ◽

pp. 263349412110235

Author(s):

Cristina Rodríguez-Varela ◽

Sonia Herraiz ◽

Elena Labarta

Keyword(s):

Stem Cells ◽

Genetic Material ◽

External Source ◽

Oocyte Quality ◽

Third Party ◽

In Vitro Fertilisation ◽

Mitochondrial Activity ◽

Mitochondrial Transfer ◽

Infertile Patients

Poor ovarian responders exhibit a quantitative reduction in their follicular pool, and most cases are also associated with poor oocyte quality due to patient’s age, which leads to impaired in vitro fertilisation outcomes. In particular, poor oocyte quality has been related to mitochondrial dysfunction and/or low mitochondrial count as these organelles are crucial in many essential oocyte processes. Therefore, mitochondrial enrichment has been proposed as a potential therapy option in infertile patients to improve oocyte quality and subsequent in vitro fertilisation outcomes. Nowadays, different options are available for mitochondrial enrichment treatments that are encompassed in two main approaches: heterologous and autologous. In the heterologous approach, mitochondria come from an external source, which is an oocyte donor. These techniques include transferring either a portion of the donor’s oocyte cytoplasm to the recipient oocyte or nuclear material from the patient to the donor’s oocyte. In any case, this approach entails many ethical and safety concerns that mainly arise from the uncertain degree of mitochondrial heteroplasmy deriving from it. Thus the autologous approach is considered a suitable potential tool to improve oocyte quality by overcoming the heteroplasmy issue. Autologous mitochondrial transfer, however, has not yielded as many beneficial outcomes as initially expected. Proposed mitochondrial autologous sources include immature oocytes, granulosa cells, germline stem cells, and adipose-derived stem cells. Presently, it would seem that these autologous techniques do not improve clinical outcomes in human infertile patients. However, further trials still need to be performed to confirm these results. Besides these two main categories, new strategies have arisen for oocyte rejuvenation by improving patient’s own mitochondrial function and avoiding the unknown consequences of third-party genetic material. This is the case of antioxidants, which may enhance mitochondrial activity by counteracting and/or preventing oxidative stress damage. Among others, coenzyme-Q10 and melatonin have shown promising results in low-prognosis infertile patients, although further randomised clinical trials are still necessary.

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Prostaglandin F2α, progesterone and estradiol concentrations in human follicular fluid and their relation to success of in vitro fertilization

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/0028-2243(88)90019-6 ◽

1988 ◽

Vol 28 (4) ◽

pp. 331-339 ◽

Cited By ~ 16

Author(s):

E. Suchanek ◽

V. Simunic ◽

E. Macas ◽

B. Kopjar ◽

V. Grizelj

Keyword(s):

In Vitro Fertilization ◽

Follicular Fluid ◽

Prostaglandin F2α ◽

Human Follicular Fluid ◽

Vitro Fertilization

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Significance of disorders of proteomic profile of follicular fluid for predicting the effectiveness of in vitro fertilisation in women with infertility

Kazan medical journal ◽

10.17816/kmj2018-496 ◽

2018 ◽

Vol 99 (3) ◽

pp. 496-503

Author(s):

O S Zolotykh ◽

S V Lomteva ◽

K Yu Sagamonova

Keyword(s):

Assisted Reproductive Technology ◽

Follicular Fluid ◽

Molecular Mechanisms ◽

Reproductive Technologies ◽

Reproductive Technology ◽

In Vitro Fertilisation ◽

Proteomic Profile ◽

Technology Programs ◽

Group 2

Aim. To study the proteomic profile of follicular fluid in patients with infertility in assisted reproductive technology programs. Methods. The study included women with infertility included in assisted reproductive technology programs: 15 women who had in vitro fertilisation which resulted in pregnancy (group 1) and 16 women with a negative result of this program (group 2). Fractionation of the follicular fluid samples was performed using the sets of special magnetic beads. Proteomic profiling was performed by tandem MALDI-mass-spectrometry. The anti-Müllerian hormone level was measured by ELISA. Results. The study revealed differences in the detectability of follicular fluid proteins with different regulatory properties in patients of groups 1 and 2. With the negative outcome of in vitro fertilisation, expression of a number of proteins involved in the processes of folliculogenesis, ovulation, selection of the dominant follicle, as well as proteins necessary for the development of the zygote and blastula was reduced in females' follicular fluid. Increased expression in women from group 2 was registered for proteins enhancing proteolytic reactions, cell apoptosis, including oocytes, which disrupt the positive action of activin and damage structural and functional state of mitochondria. A definite relationship was found between the level of anti-Müllerian hormone and rate of detection of a number of proteins, in particular protocadherin-2α, cystatin C, betaglycan, prostatic acid phosphatase, and dermicidin. Conclusion. The revealed changes in proteomic profile of the follicular fluid obviously play an important role in the molecular mechanisms that determine the effectiveness of assisted reproductive technologies; the identified differentially expressed proteins can serve as objective markers for predicting the outcomes of in vitro fertilisation.

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The proteomics of human follicular fluid on the day of oocyte retrieval in in vitro fertilization cycle

Fertility and Sterility ◽

10.1016/j.fertnstert.2018.07.675 ◽

2018 ◽

Vol 110 (4) ◽

pp. e235-e236

Author(s):

H. Wang ◽

X. Guo ◽

R. Wang

Keyword(s):

In Vitro Fertilization ◽

Follicular Fluid ◽

Oocyte Retrieval ◽

Human Follicular Fluid ◽

Vitro Fertilization

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Cytokine antibody array profiling in human follicular fluid as a potential marker for oocyte quality

Fertility and Sterility ◽

10.1016/j.fertnstert.2016.07.554 ◽

2016 ◽

Vol 106 (3) ◽

pp. e187

Author(s):

M. Pavone ◽

J.M. Kelsh ◽

S. Malpani ◽

R. Confino ◽

S. Jasti ◽

...

Keyword(s):

Follicular Fluid ◽

Oocyte Quality ◽

Antibody Array ◽

Human Follicular Fluid ◽

Potential Marker ◽

Cytokine Antibody Array

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2 SPECIFIC FATTY ACID FOLLOW-UP REVEALS RUMEN-PROTECTED FAT SUPPLEMENTATION EFFECTS ON BOVINE OOCYTE QUALITY AND EMBRYO DEVELOPMENT

Reproduction Fertility and Development ◽

10.1071/rdv26n1ab2 ◽

2014 ◽

Vol 26 (1) ◽

pp. 115 ◽

Cited By ~ 1

Author(s):

A. F. González-Serrano ◽

C. R. Ferreira ◽

V. Pirro ◽

J. Heinzmann ◽

K.-G. Hadeler ◽

...

Keyword(s):

Fatty Acid ◽

Palmitic Acid ◽

Embryo Development ◽

Follicular Fluid ◽

Oocyte Quality ◽

Lipid Profiles ◽

Dependent Manner ◽

Fat Supplementation

Information on how supplementation of high-yield dairy cows with rumen-protected fat affects fertility in cattle herds is scarce. Here, Holstein-Friesian heifers (n = 84) received a supplement consisting of either rumen-protected conjugated linoleic acid (CLA; cis-9,trans-11-CLA and trans-10,cis-12-CLA) or stearic acid 18 : 0 (SA) on top of an isocaloric grass silage diet. Two supplementation doses were used (100 and 200 g d–1). Blood and follicular fluid were collected at the start and end of the supplementation period for analysis of cholesterol, insulin-like growth factor (IGF), and nonesterified fatty acids (NEFA), and for fatty acid profiling. Although cholesterol, IGF, and NEFA levels did not differ among experimental groups, lipid profiles in blood and follicular fluid were affected in a dose-dependent manner by both supplements. After 45 days of supplementation, oocytes were collected by ovum pick-up (OPU). The mRNA relative abundance of target genes (IGF1r, GJA1, FASN, SREBP1, and SCAP) was analysed in single in vitro- (24 h IVM) and in vivo-matured (collected by OPU 20 h after GnRH injection) oocytes and in vitro-produced blastocysts (Day 8) by qPCR (n = 6/group). Lipid profiling of individual oocytes from the CLA-supplemented (n = 37) and the SA-supplemented (n = 50) was performed by desorption electrospray ionization mass spectrometry (DESI-MS). Oocytes from the CLA-supplemented (n = 413) and the SA-supplemented (n = 350) groups were used for assessing maturation and blastocysts development rates. In immature oocytes, CLA supplementation led to an increase of triacylglycerol 52 : 3 [TAG (52 : 3)] and TAG (52 : 2), squalene, palmitic acid 16 : 0, and oleic acid 18 : 1, and decreased abundance of TAG (56 : 3), TAG (50 : 2) and TAG (48 : 1). In vitro-matured oocytes showed different lipid profiles, with increased abundances of TAG (52 : 3), and TAG (52 : 2) as well as phosphatidylinositol 34 : 1 [Plo (34 : 1)], whereas phosphatidylglycerol (34 : 1) [PG (34 : 1)] and palmitic acid 16 : 0 were less abundant in in vitro-matured oocytes. SCAP was significantly down-regulated in in vitro-matured oocytes from supplemented heifers compared with their in vivo-matured counterparts. Maturation (CLA = 74% v. SA = 67%) and blastocyst rates (CLA = 22.4% v. SA = 12.7%) were different among experimental groups. One-way ANOVA and the Tukey-Kramer test were applied for a multiple comparison of means (P-value ≤ 0.05 was considered as statistically significant). In conclusion, we demonstrate here that fatty acid monitoring along different compartments (i.e. blood system, follicular fluid, and intra-oocyte) after rumen-protected fat supplementation of dairy heifer diet reveals nutritional footprints on oocyte quality and embryo development. These results demonstrate the close relationship between nutrition and cattle herd's fertility and, at the same time, support the role of the bovine model for understanding nutritional-dependent fertility impairments.

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