Proteomic analysis of human follicular fluid from fertile women

Zamah, A.M.; Hassis, Maria E.; Albertolle, Matthew E.; Williams, Katherine E.

doi:10.1186/s12014-015-9077-6

Cited by 114 publications

(113 citation statements)

References 100 publications

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“…After three washes with the PBS-EDTA solution, organoids were solubilized in 8 M urea containing Complete protease inhibitor mixture (Roche) and were clarified by centrifugation for 10 min at 16,500 × g. Fifty micrograms of protein extract from mammary organoids were trypsin digested and labeled with iTRAQ 8plex reagent (Sigma-Aldrich) as previously described (Fig. 1A) (83).…”

Section: Methodsmentioning

confidence: 99%

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Williams

Lemieux

Hassis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastomaassociated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation.proteomics | mammary epithelium | environmental chemicals | organotypic culture | estrogen B reast cancers are caricatures of normal tissue development (1-3). The same underlying mechanisms that affect the cell processes needed for normal mammary development contribute to cancer progression. By affecting the distribution of interacting cells and communication among them through nontargeted effects, carcinogens can promote the outgrowth of altered cells with malignant potential. Exposure to environmental agents can affect mammary gland development and alter breast cancer risk. Epidemiologic studies have associated a number of environmental factors with increased breast cancer risk (4). Some of these factors may have low-level effects that are not genotoxic but alter immune responses, vascularity, or the microenvironment or that change susceptibility to carcinogens. A current weakness in models of cancer risk assessment is the lack of consideration of factors that influence the susceptibility of mixed cell populations to transformation. Indeed, ionizing radiation, the prototypical carcinogen, promotes changes in the biochemical properties in cultured mouse and human breast cells, in the stromal environment, and in intact mouse mammary gland (5-7).Physiologically relevant 3D culture models can recapitulate crucial aspects of the dynamic and reciprocal signaling necessary for establishing and maintaining tissue-specific morphogenetic programs. The determination of the molecular mechanisms underlying m...

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Section: Methodsmentioning

confidence: 99%

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Williams

Lemieux

Hassis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The follicular fluid (FF) surrounds the oocyte and its composition is profoundly influenced by the granulosa cell secretions, functioning as a mediator of signalling substances that are transported between cell types within the follicle and the surroundings [7]. In women undergoing assisted reproductive technologies, FF is easily accessible, allowing analysis of hormones and granulosa cell gene expression to determine the impact of ovarian stimulation and the maturation trigger on oocyte maturation.…”

Section: Introductionmentioning

confidence: 99%

Effect of GnRHa ovulation trigger dose on follicular fluid characteristics and granulosa cell gene expression profiles

Vuong

et al. 2017

J Assist Reprod Genet

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Purpose A recent dose-finding study showed no significant differences in number of mature oocytes, embryos and topquality embryos when triptorelin doses of 0.2, 0.3 or 0.4 mg were used to trigger final oocyte maturation in oocyte donors co-treated with a gonadotropin-releasing hormone (GnRH) antagonist. This analysis investigated whether triptorelin dosing for triggering final oocyte maturation in oocyte donors induced differences in follicular fluid (FF) hormone levels and granulosa cell gene expression. Methods This single-centre, randomised, parallel, investigatorblinded trial was conducted in oocyte donors undergoing a single stimulation cycle at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam, from August 2014 to March 2015.A total of 165 women aged 18-35 years with body mass index <28 kg/m 2 , anti-Müllerian hormone >1.25 ng/mL, and antral follicle count ≥6 were randomised to three different triptorelin doses for trigger. The main outcome was concentration of steroid hormones in FF collected from the first punctured follicle on each side. Moreover, luteinising hormone receptor (LHR), 3β-hydroxy-steroid-dehydrogenase (3ßHSD) and inhibin-Ba (INHB-A) gene expression in cumulus and mural granulosa cells were investigated in a subset of women from each group. Results Progesterone and oestradiol levels in FF did not differ significantly by trigger doses; findings were similar for 3βHSD, LHR and INHB-A gene expression in both cumulus and mural granulosa cells. Conclusions In women co-treated with a GnRH antagonist, no significant differences in FF steroid levels and granulosa cell gene expression were seen when different triptorelin doses were used to trigger final oocyte maturation.

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“…Application of powerful proteomic and peptidomic technologies in reproductive medical research may significantly contribute to help diagnosis but also the comprehensive understanding of reproductive processes. Several laboratories have demonstrated the feasibility of selecting peptide/protein diagnostic biomarkers in follicular fluid [20–22]. …”

Section: Introductionmentioning

confidence: 99%

Follicular fluid biomarkers for human in vitro fertilization outcome: Proof of principle

et al. 2016

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BackgroundHuman follicular fluid (FF) is a unique biological fluid in which the oocyte develops in vivo, and presents an optimal source for non-invasive biochemical predictors. Oocyte quality directly influences the embryo development and hence, may be used as a predictor of embryo quality. Peptide profiling of FF and its potential use as a biomarker for oocyte quality has never been reported.MethodsThis study screened FF for peptide biomarkers that predict the outcome of in vitro fertilization (IVF). Potential biomarkers were discovered by investigating 2 training datasets, consisting both of 17 samples and validating on an independent experiment containing 32 samples. Peptide profiles were acquired by nano-scale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS).ResultsFrom the training datasets 53 peptides were found as potential biomarker candidates, predicting the fertilization outcome of 24 out of the 32 validation samples blindly (81.3% sensitivity, 68.8% specificity, AUC = 0.86). Seven potential biomarker peptides were identified. They were derived from: insulin-like growth factor binding protein-5, alpha-2-antiplasmin, complement component 3, inter-alpha-trypsin inhibitor heavy chain H1, serum albumin, protein diaphanous homolog 1 and plastin-3.ConclusionsThe MS-based comprehensive peptidomic approach carried out in this study, established a novel panel of potential biomarkers that present a promising predictive accuracy rate in fertilization outcome, and indicates FF as an interesting biomarker resource to improve IVF clinic routine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-016-0106-9) contains supplementary material, which is available to authorized users.

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Proteomic analysis of human follicular fluid from fertile women

Cited by 114 publications

References 100 publications

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Effect of GnRHa ovulation trigger dose on follicular fluid characteristics and granulosa cell gene expression profiles

Follicular fluid biomarkers for human in vitro fertilization outcome: Proof of principle

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