Dataset Information

A Tale of Two Follicles: Proteomic Clues to Oocyte Success and Failure

ABSTRACT: Women are born with thousands of follicles in their ovaries but less than 1% will produce a mature oocyte. What distinguishes the 99% of ovarian follicles destined for demise from the rare 1% that succeed? Here, we leveraged a unique clinical opportunity, paired follicular fluid samples from small antral follicles containing viable and atretic oocytes, to uncover the proteomic determinants governing oocyte fate. Our analysis identified nearly 1,500 proteins, revealing that healthy follicular fluid is enriched with proteins crucial for energy metabolism, antioxidative defense, structural integrity, and robust signaling networks, supporting successful oocyte survival and maturation. In contrast, atretic follicles exhibited a distinct inflammatory signature characterized by acute-phase and immune activation proteins, indicative of active degeneration. These novel proteomic insights deepen our understanding of follicle biology and open new avenues for biomarker development, optimization of assisted reproductive technologies, and targeted therapeutic strategies to preserve and enhance female fertility.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Follicular Fluid

SUBMITTER: Jeovanis Gil

LAB HEAD: Jeovanis Gil

PROVIDER: PXD063187 | Pride | 2026-03-30

REPOSITORIES: Pride

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Publications

Molecular signatures of oocyte viability identified by follicular fluid proteomics.

Kristensen Stine Gry SG Subiran Adrados Cristina C Elsner Kevin K Cadenas Jesus J Jensen Lea Bejstrup LB Tanvig Mette Honnens MH Greve Vinnie Hornshøj VH Colmorn Lotte Berdiin LB Marko-Varga György G Malm Johan J Gil Jeovanis J

Scientific reports 20260220 1

Women are born with thousands of ovarian follicles, yet less than 1% will ovulate a mature oocyte. What distinguishes the 99% of follicles destined for demise from the rare 1% that succeed? Here, we leveraged a unique clinical opportunity, paired follicular fluid samples from small antral follicles containing either a viable or an atretic oocyte within the same patients, to uncover the proteomic determinants governing oocyte fate. Our analysis identified nearly 1,500 proteins. Follicular fluid f ...[more]

PMID: 41720862

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Project description:The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor Î± (TNFÎ±) and other immune factors, are produced and act on the reproductive system. However, TNFÎ± is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNFÎ± in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta). In control and recombinant trout TNFÎ± (rtTNFÎ±)-treated granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI) staining. Furthermore, we determined the in vitro effects of rtTNFÎ± on follicle contraction and testosterone production in preovulatory trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNFÎ±-treated ovarian tissue by microarray and real-time PCR (qPCR) analyses.Treatment with rtTNFÎ± induces ovarian cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNFÎ± causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNFÎ± induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. In view of these results, we propose that TNFÎ± could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction. Reproductively mature female brown trout (Salmo trutta) from a cultured stock at the Piscifactoria de BagÃ (Generalitat de Catalunya, BagÃ , Spain) were kept under natural conditions of temperature and photoperiod. Fish at the preovulatory stage (according to the position of the germinal vesicle (GV) in oocytes that were cleared using a solution previously described), were anesthesized in 3-aminobenzoic acid ethyl ester (0.1 g/l; Sigma, Alcobendas, Spain) dissolved in fresh water, and the fish were sacrificed by concussion prior to the collection of the ovaries. The dissected ovaries were immediately used for the various in vitro assays. After dissection, brown trout preovulatory ovaries were placed in HankÂ´s balanced salt solution (HBSS) and individual ovarian follicles were manually separated with forceps from each ovary on ice, as previously described. To collect ovarian tissue for RNA extraction, preovulatory follicles from each of a total of three females were incubated (400 follicles/50 ml) in HBSS-BSA in the absence or presence of rtTNFÎ± (100 ng/ ml, dissolved directly in HBSS-BSA), at 15ÂºC for 24 h with gentle shaking (100 rpm). At the end of the incubation follicles (previously de-yolked by gentle pressure) were removed, flash frozen in liquid nitrogen and stored at -80ÂºC until assayed.

Project description:MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression primarily at the post-transcriptional levels and thereby play important roles in regulating many physiological and developmental processes. Oocyte maturation in fish is induced by hormones produced from the hypothalamus, pituitary, and ovary. Gonadotropin-releasing hormone (GnRH) stimulates the secretion of luteinizing hormone (LH), which in turn, induces the secretion of maturation-inducing hormone (MIH) from the ovary. It is documented that small early vitellogenic (or stage IIIa) follicles are unable to undergo oocyte maturation whereas oocytes in mid- to late vitellogenic (stage IIIb) follicles can be induced by LH and MIH to become mature. To determine whether miRNAs may be involved in the growth and acquisition of maturational competency of ovarian follicles, we determined the miRNA expression profiles in follicular cells collected from stage IIIa and IIIb follicles using next-generation sequencing. It was found that miRNAs are abundantly expressed in the follicular cells from both stages IIIa and IIIb follicles. Furthermore, bioinformatics analysis revealed the presence of 214 known, 31 conserved novel and 44 novel miRNAs in zebrafish vitellogenic ovarian follicular cells. Most mature miRNAs in follicular cells were found to be in the length of 22 nucleotides. Differential expression analysis revealed that 11 miRNAs were significantly up-regulated, and 13 miRNAs were significantly down-regulated in the stage IIIb follicular cells as compared with stage IIIa follicular cells. The expression of four of the significantly regulated miRNAs, dre-miR-22a-3p, dre-miR-16a, dre-miR-181a-3p, and dre-miR-29a, was validated by real-time PCR. Finally, gene enrichment and pathway analyses of the predicted targets of the significantly regulated miRNAs supported the involvement of several key signaling pathways in regulating ovarian function, including oocyte maturation. Taken together, this study identifies novel zebrafish miRNAs and characterizes miRNA expression profiles in somatic cells within the zebrafish ovarian follicles. The differential expression of miRNAs between stage IIIa and IIIb follicular cells suggests that these miRNAs are important regulators of zebrafish ovarian follicle development and/or oocyte maturation.

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