scholarly journals Polybrominated Diphenyl Ethers in Human Follicular Fluid Dysregulate Mural and Cumulus Granulosa Cell Gene Expression

Endocrinology ◽  
2021 ◽  
Author(s):  
Pavine L C Lefèvre ◽  
Thomas C Nardelli ◽  
Weon-Young Son ◽  
Amy R Sadler ◽  
Dorothea F K Rawn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Polybrominated Diphenyl Ethers ◽  
Cell Function ◽  
Consumer Products ◽  
Environmental Chemicals ◽  
Diphenyl Ethers

Abstract Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants incorporated into numerous consumer products, leach out into dust resulting in widespread exposure. There is evidence from in vitro and in vivo animal studies that PBDEs affect ovarian granulosa cell function and follicular development, yet human studies of their association with female infertility are inconclusive. Here, we tested the hypothesis that exposure to the PBDEs in follicular fluid is associated with dysregulation of gene expression in the mural and cumulus granulosa cells collected from women undergoing in vitro fertilization by intracytoplasmic sperm injection. The median concentration of the ∑10PBDEs detected in the follicular fluid samples (n=37) was 15.04 pg/g wet weight. RNA microarray analyses revealed that many genes were differentially expressed in mural and cumulus granulosa cells. Highest vs. lowest quartile exposure to the Σ10PBDEs or to two predominant PBDE congeners, BDE-47 or BDE-153, was associated with significant effects on gene expression in both cell types. Mural granulosa cells were generally more sensitive to PBDE exposure compared to cumulus cells. Overall, gene expression changes associated with BDE-47 exposure were similar to those for ∑10PBDEs but distinct from those associated with BDE-153 exposure. Interestingly, exposure to BDE-47 and ∑10PBDEs activated the expression of genes in pathways that are important in innate immunity and inflammation. To the best of our knowledge, this is the first demonstration that exposure to these environmental chemicals is associated with the dysregulation of pathways that play an essential role in ovulation.

scholarly journals The role of IGFs in the regulation of ovarian follicular growth in the brushtail possum (Trichosurus vulpecula)

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 295-303 ◽  
Author(s):  
Jennifer L Juengel ◽  
Lisa J Haydon ◽  
Brigitta Mester ◽  
Brian P Thomson ◽  
Michael Beaumont ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Antral Follicle ◽  
Brushtail Possum ◽  
Follicular Growth ◽  
Theca Cells ◽  
Ovarian Follicular Growth

IGFs are known to be key regulators of ovarian follicular growth in eutherian mammals, but little is known regarding their role in marsupials. To better understand the potential role of IGFs in the regulation of follicular growth in marsupials, expression of mRNAs encoding IGF1, IGF2, IGF1R, IGF-binding protein 2 (IGFBP2), IGFBP4 and IGFBP5 was localized by in situ hybridization in developing ovarian follicles of the brushtail possum. In addition, the effects of IGF1 and IGF2 on granulosa cell function were tested in vitro. Both granulosa and theca cells synthesize IGF mRNAs, with the theca expressing IGF1 mRNA and granulosa cell expressing IGF2 mRNA. Oocytes and granulosa cells express IGF1R. Granulosa and theca cells expressed IGFBP mRNAs, although the pattern of expression differed between the BPs. IGFBP5 mRNA was differentially expressed as the follicles developed with granulosa cells of antral follicles no longer expressing IGFBP5 mRNA, suggesting an increased IGF bioavailability in the antral follicle. The IGFBP protease, PAPPA mRNA, was also expressed in granulosa cells of growing follicles. Both IGF1 and IGF2 stimulated thymidine incorporation but had no effect on progesterone production. Thus, IGF may be an important regulator of ovarian follicular development in marsupials as has been shown in eutherian mammals.

scholarly journals Expression of mRNAs for Pro-and Anti-Apoptotic Factors in Granulosa Cells and Follicular Fluid of Women Undergoing in Vitro Fertilization. A Pilot Study

2021 ◽  
Author(s):  
Jozsef Bodis ◽  
Endre Sulyok ◽  
Akos Varnagy ◽  
Viktória Prémusz ◽  
Krisztina Godony ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Vitro Fertilization ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Vitro Fertilization ◽  
Expression Levels ◽  
The Impact ◽  
Apoptotic Factors

Abstract BackgroundThis observational clinical study evaluated the expression levels and predictive values of some apoptosis-related genes in granulosa cells (GCs) and follicular fluid (FF) of women undergoing in vitro fertilization (IVF).Methods GCs and FF were obtained at oocyte retrieval from 31 consecutive patients with heterogeneous infertility diagnosis (age: 34.3±5.8 years, body mass index: 24.02±3.12 kg/m2, duration of infertility: 4.2±2.1 years). mRNA expression of pro-apoptotic (BAX, CASP3, CASP8) and anti-apoptotic (BCL2, AMH, AMHR, FSHR, LHR, CYP19A1) factors was determined by quantitative RT-PCR using ROCHE LightCycler 480. Results No significant difference in GC or FF mRNA expression of pro- and anti-apoptotic factors could be demonstrated between IVF patients with (9 patients) or without (22 patients) clinical pregnancy. Each transcript investigated was detected in FF, but their levels were markedly reduced and independent of those in GCs. The number of retrieved oocytes was positively associated with GC AMHR (r=0.393, p=0.029), but the day of embryo transfer was negatively associated with GC LHR (r=-0.414, p=0.020) and GC FSHR transcripts (r=-0.535, p=0.002). When pregnancy positive group was analysed separately the impact of apoptosis- related gene expressions on some selected measures of IVF success could be observed. Strong positive relationship was found between gene expression levels of pro- and anti-apoptotic factors in GCs.ConclusionOur study provides only marginal evidences for the apoptosis dependence of IVF outcome and suggests that the apoptosis process induces adaptive increases of the anti-apoptotic gene expression to attenuate apoptosis and to protect cell survival.

scholarly journals Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles

Reproduction ◽  
2009 ◽  
Vol 137 (5) ◽  
pp. 843-855 ◽  
Author(s):  
Martha Z Carletti ◽  
Lane K Christenson
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Signaling ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Egf Receptor ◽  
Cell Function ◽  
Early Response ◽  
Cell Gene Expression

LH acts on periovulatory granulosa cells by activating the PKA pathway as well as other cell signaling cascades to increase the transcription of specific genes necessary for ovulation and luteinization. Collectively, these cell signaling responses occur rapidly (within minutes); however, presently no high throughput studies have reported changes before 4 h after the LH surge. To identify early response genes that are likely critical for initiation of ovulation and luteinization, mouse granulosa cells were collected before and 1 h after hCG. Fifty-seven gene transcripts were significantly (P<0.05) upregulated and three downregulated following hCG. Twenty-four of these transcripts were known to be expressed after the LH/hCG surge at later time points, while 36 were unknown to be expressed by periovulatory granulosa cells. Temporal expression of several transcripts, including the transcription factorsNr4a1,Nr4a2,Egr1,Egr2,Btg1, andBtg2, and the epidermal growth factor (EGF)-like ligandsAregandEreg, were analyzed by quantitative RT-PCR, and their putative roles in granulosa cell function are discussed. Epigen (Epgn), another member of the family of EGF-like ligands was identified for the first time in granulosa cells as rapidly induced by LH/hCG. We demonstrate thatEpgninitiates cumulus expansion, similar to the other EGF-receptor ligandsAregandEreg. These studies illustrate that a number of changes in gene expression occurin vivoin response to LH, and that many of the differentially expressed genes are transcription factors that we would predict in turn modulate granulosa cell gene expression to ultimately impact the processes of ovulation and luteinization.

Oocyte-secreted factros regulate granulosa cell steroidogenesis

Zygote ◽  
1996 ◽  
Vol 4 (04) ◽  
pp. 317-321 ◽  
Author(s):  
Barbara C. Vanderhyden
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Follicular Development ◽  
Inhibitory Factor ◽  
Preovulatory Follicles ◽  
Loss Of Contact

Investigations of strains of mice defective in germ cell development have revealed the importance of oocytes for the initial stages of folliculogenesis (Pellaset al., 1991; Huanget al., 1993). Various aspects of follicular development are dependent upon and/or influenced by the presence of oocytes, including granulosa cell proliferation (Vanderhydenet al., 1990, 1992) and cumulus expansion (Buccioneet al., 1990; Salustriet al., 1990; Vanderhydenet al., 1990; Vanderhyden, 1993). We are investigating the possibility that oocytes influence one of the primary functions of granulosa cells: steroidogenesis. In many species, granulosa cells removed from preovulatory follicles luteinisein vitro(Channinget al., 1982), presumably due to loss of contact with follicular luteinisation inhibitory factor(s). Indeed, follicular fluid can prevent granulosa cell luteinisationin vitro(Ledwitz-Rigbyet al., 1977). Follicular fluid, however, may simply be the medium for transport of factors secreted by oocytes to regulate granulosa cell activities.

SERUM AND FOLLICULAR FLUID CONCENTRATIONS OF POLYBROMINATED DIPHENYL ETHERS (PBDEs) AND IN-VITRO FERTILIZATION (IVF) OUTCOME

2011 ◽  
Vol 2011 (1) ◽  
Author(s):  
Paula I. Johnson ◽  
Larisa Altshul ◽  
Daniel W. Cramer ◽  
Stacey A. Missmer ◽  
Russ Hauser ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Follicular Fluid ◽  
Polybrominated Diphenyl Ethers ◽  
Ivf Outcome ◽  
Vitro Fertilization ◽  
Diphenyl Ethers

Is nitric oxide an autocrine modulator of bovine granulosa cell function?

1998 ◽  
Vol 10 (6) ◽  
pp. 471 ◽  
Author(s):  
G. Basini ◽  
M. Baratta ◽  
N. Ponderato ◽  
S. Bussolati ◽  
C. Tamanini
Keyword(s):  
Nitric Oxide ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Cell Function ◽  
Lead Point ◽  
No Donor ◽  
Cells In Culture ◽  
Proliferation And Apoptosis ◽  
Cellular Apoptosis

Nitric oxide (NO) is an important intra- and intercellular messenger controlling many biological processes. It is synthesized by NO synthases, which have been found also in granulosa cells. The present study examined whether NO is present in bovine follicular fluid and is produced by granulosa cells in culture. Secondly, it aimed to determine if NO affects the main parameters of granulosa cell function. The NO donor S-nitroso-L-acetyl-penicillamine (10 –3 , 10 –4 , 10 –5 М) was used to evaluate whether NO might influence steroidogenesis, proliferation and apoptosis in bovine granulosa cells collected from follicles divided according to their size in small (<5 mm) and large (>8 mm). The data demonstrate the presence of NO in follicular fluid and its production by granulosa cells in culture: the most active cells in producing NO are those from the small follicles, as confirmed by the NO levels in follicular fluid. This study also shows that NO donor significantly (P<0.001) inhibits progesterone (P4) and oestradiol 17β (E2) production by the granulosa cells from both kinds of follicle; moreover, the highest concentration of NO donor significantly (P<0.001) inhibits DNA fragmentation in all the cells whereas the lowest concentration stimulates (P<0.001) cellular apoptosis only in granulosa cells from large follicles. NO donor does not seem to modify cell proliferation. Taken together these data lead point to NO as a local modulator of granulosa cell function.

scholarly journals Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle

Reproduction ◽  
2017 ◽  
Vol 153 (2) ◽  
pp. R69-R83 ◽  
Author(s):  
Richard J Kordus ◽  
Holly A LaVoie
Keyword(s):  
Gene Expression ◽  
Granulosa Cell ◽  
Live Birth ◽  
Granulosa Cells ◽  
Expression Profiles ◽  
Ovarian Follicle ◽  
Critical Discussion ◽  
Developmental Competence ◽  
Published Data

Cumulus and mural granulosa cells of the ovarian follicle surround and interact with the developing oocyte. These follicular cells reflect the oocyte’s overall health and may indicate subsequent developmental competence of embryos. Biomarkers of granulosa cells associated with individual oocytes could potentially be used in assisted reproduction to indicate which embryos have the best chance of implanting in the uterus and completing gestation. In this review, we have performed a comprehensive assessment of the recent literature for human cumulus and mural granulosa cell mRNA biomarkers as they relate to pregnancy and live birth. A critical discussion of variables affecting granulosa gene expression profiles for in vitro fertilization patients, including patient demographics and ovarian stimulation regimens, is presented. Although studies with microarray data were evaluated, this synopsis focuses on expressed genes that have been validated by quantitative RT-PCR. Furthermore, we summarize the current published data that support or refute identified granulosa expressed genes as potential biomarkers of embryos that give rise to ongoing pregnancy and live birth. Finally, we review studies that offer predictive models for embryo selection for uterine transfer based on biomarkers that show differential gene expression.

scholarly journals Expression of mRNAs for pro-and anti-apoptotic factors in granulosa cells and follicular fluid of women undergoing in vitro fertilization. A pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
József Bódis ◽  
Endre Sulyok ◽  
Ákos Várnagy ◽  
Viktória Prémusz ◽  
Krisztina Gödöny ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Vitro Fertilization ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Vitro Fertilization ◽  
Expression Levels ◽  
The Impact ◽  
Apoptotic Factors

Abstract Background This observational clinical study evaluated the expression levels and predictive values of some apoptosis-related genes in granulosa cells (GCs) and follicular fluid (FF) of women undergoing in vitro fertilization (IVF). Methods GCs and FF were obtained at oocyte retrieval from 31 consecutive patients with heterogeneous infertility diagnosis (age: 34.3 ± 5.8 years, body mass index: 24.02 ± 3.12 kg/m2, duration of infertility: 4.2 ± 2.1 years). mRNA expression of pro-apoptotic (BAX, CASP3, CASP8) and anti-apoptotic (BCL2, AMH, AMHR, FSHR, LHR, CYP19A1) factors was determined by quantitative RT-PCR using ROCHE LightCycler 480. Results No significant difference in GC or FF mRNA expression of pro- and anti-apoptotic factors could be demonstrated between IVF patients with (9 patients) or without (22 patients) clinical pregnancy. Each transcript investigated was detected in FF, but their levels were markedly reduced and independent of those in GCs. The number of retrieved oocytes was positively associated with GC AMHR (r = 0.393, p = 0.029), but the day of embryo transfer was negatively associated with GC LHR (r = − 0.414, p = 0.020) and GC FSHR transcripts (r = − 0.535, p = 0.002). When pregnancy positive group was analysed separately the impact of apoptosis- related gene expressions on some selected measures of IVF success could be observed. Strong positive relationship was found between gene expression levels of pro- and anti-apoptotic factors in GCs. Conclusion Our study provides only marginal evidences for the apoptosis dependence of IVF outcome and suggests that the apoptosis process induces adaptive increases of the anti-apoptotic gene expression to attenuate apoptosis and to protect cell survival.

scholarly journals Serum and follicular fluid concentrations of polybrominated diphenyl ethers and in-vitro fertilization outcome

2012 ◽  
Vol 45 ◽  
pp. 9-14 ◽  
Author(s):  
Paula I. Johnson ◽  
Larisa Altshul ◽  
Daniel W. Cramer ◽  
Stacey A. Missmer ◽  
Russ Hauser ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Follicular Fluid ◽  
Polybrominated Diphenyl Ethers ◽  
Vitro Fertilization ◽  
Diphenyl Ethers
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