Apoptosis in bovine cumulus–oocyte complexes after exposure to polychlorinated biphenyl mixtures during in vitro maturation

Pocar, Paola; Nestler, D.; Risch, Michaela; Fischer, Bernd

doi:10.1530/rep.1.00761

Cited by 37 publications

(18 citation statements)

References 51 publications

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“…Furthermore, we observed that in the presence of bNF a significant increase in cumulus cells apoptosis occurs only in the absence of follicular fluid, whereas no difference was observed in the presence of the latter compared with control, indicating that apoptosis may be at the basis of the ovotoxicity observed. These data are in agreement with previous results in bovine COCs, indicating that PCB 126, another potent AhR-ligand, induces apoptosis in cumulus cell mass (Pocar et al 2005). Several studies implicate the AhR as having a role in modulating or mediating apoptotic processes.…”

Section: Discussionsupporting

confidence: 93%

Regulation of aryl hydrocarbon receptor activity in porcine cumulus–oocyte complexes in physiological and toxicological conditions: the role of follicular fluid

Nestler¹,

Risch²,

Fischer³

et al. 2007

Reproduction

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The arylhydrocarbon receptor (AhR) mediates the adverse effects of dioxin-like compounds. However, it has also been reported that the AhR may exert a role in ovarian physiology. In the present study, porcine cumulus-oocyte complexes (COCs) were matured in vitro in the presence of 10% follicular fluid. Expression of AhR and its partner, AhR nuclear translocator occurs in immature COCs. After in vitro maturation (IVM), an up-regulation of AhR and cytochrome P450 1A1 (CYP1A1; the main AhRtarget gene) was observed. To explore the role of the AhR during IVM, we exposed the COCs to 50 mM b-napthoflavone (bNF). The treatment induced a marked up-regulation of CYP1A1 mRNA, indicating both constitutive and inducible AhR activity. However, in contrast to what was observed in other cell types, no sign of toxicity was observed in COCs. To investigate if components of porcine follicular fluid may exert a protective role against AhR ligands, we exposed porcine COCs to bNF, in the absence of follicular fluid. In these conditions, a marked decrease in the percentage of matured oocytes, concomitant with an increase in oocyte degeneration, was observed. Furthermore, bNF increased apoptosis in cumulus cells in the absence of follicular fluid, whereas bNF has no effects when COCs were treated in the presence of porcine follicular fluid (pFF). In conclusion, these results suggest the presence of unknown endogenous AhR-ligand(s) during porcine IVM and that a dysregulation of this mechanism may result in ovotoxicity by inducing apoptosis in cumulus cells. However, this phenomenon is interrupted by the presence of follicular fluid, indicating a putative protective role for follicular fluid components against exogenous insults.

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Section: Discussionsupporting

confidence: 93%

Regulation of aryl hydrocarbon receptor activity in porcine cumulus–oocyte complexes in physiological and toxicological conditions: the role of follicular fluid

Nestler¹,

Risch²,

Fischer³

et al. 2007

Reproduction

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“…Signaling molecules in the regulation of the apoptosis are distributed among cells in the COCs [22]. One key signaling cascade regulated by FSH-FSHR interaction is the production of second messenger molecules (cAMP) and IP3.…”

Section: Discussionmentioning

confidence: 99%

FSHR and LHR Expression and Signaling as Well as Maturation and Apoptosis of Cumulus-Oocyte Complexes Following Treatment with FSH Receptor Binding Inhibitor in Sheep

Wei

Shen

Gong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Currently, it remains unknown whether FSH receptor binding inhibitor (FRBI) influences follicular development and reproduction functions in humans and animals. The present study aimed to investigate FRBI effects on in vitro maturation (IVM) and apoptosis of cumulus-oocyte complexes (COCs) of sheep, to determine the effect of FRBI on mRNA and protein levels of FSHR and LHR in COCs, and to elucidate the signal pathway of FRBI effects. Methods: COCs were in vitro cultured for 24h in the IVM media supplemented with varying concentrations of FRBI (0, 10, 20, 30 and 40µg/mL) and FSH (10IU/mL). The harvested COCs were observed under an inverted microscope and maturation rates of COCs were determined. Real time RT-PCR and Western blotting were utilized to detect mRNA and protein levels of FSHR and LHR. The concentrations of FSH, LH and caspase-3 were determined using especial ELISA kits for sheep, respectively. Results: Maturation rates of COCs decreased gradually as FRBI concentrations increased from 0 to 40µg/mL, reaching a bottom value of 23.76% of the FRBI-4 group. The maximal apoptosis rate was detected in the FRBI-4 group. IP3 contents of FRBI-3 and FRBI-4 groups were reduced as compared to control group (CG) and FSH groups (P<0.05). Levels of FSHR protein of FRBI-3 and FRBI-4 groups as well as LHR protein of FRBI-4 group were significantly less than that of CG and FSH group. FSH contents of four FRBI treatment groups were gradually decreased along with the supplementation doses of FRBI. Caspase-3 contents of FRBI groups were reduced with a maximum reduction of the FRBI-2 group. Conclusion: Our results revealed supplement of FRBI into IVM media could dose-dependently decrease the maturation rate and increase apoptosis rate of sheep COCs. A lower dose of FRBI treatment slightly promoted IP3 production, but a higher dose of FRBI reduced IP3 production. FRBI suppressed the mRNA and protein expression levels of FSHR and LHR in sheep COCs. Our study will help to therapy effectively ovarian diseases, improve ovarian and follicular functions, and further to promote fertility of humans and animals.

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“…Aroclor 1254 inhibited in the vitro maturation and development competence of bovine oocytes [22] as well as inducing cumulus cell apoptosis [23]. Furthermore, adverse effects of exposure to Aroclor 1254 during oocyte maturation were extended to fertilization and embryonic development [8].…”

Section: Discussionmentioning

confidence: 99%

Effects of Aroclor 1254 on In Vivo Oocyte Maturation in the Mouse

et al. 2014

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Polychlorinated biphenyls (PCBs) are stable, lipophilic compounds that accumulate in the environment and in the food chain. Though some studies provided evidence that PCBs had adverse effects on reproductive function, most of these results were from in vitro models. Therefore we investigated the effect of Aroclor 1254 (a commercial PCBs mixture) treatments on in vivo maturation and developmental potential of mouse oocytes. In the present study, female ICR mice were treated with different doses (12.5, 25 and 50 mg/kg) of Aroclor 1254 (a commercial PCB mixture) once every 72 hours by intraperitoneal injection for 9 days. After three treatments of Aroclor 1254, the mice were superovulated to collect oocytes one day after the last exposure. The effects of Aroclor 1254 on oocyte maturation, fertilization, and preimplantation embryonic development were investigated. Immunofluorescence-stained oocytes were observed under a confocal microscope to assess the effects of Aroclor 1254 on spindle morphology. Parthenogenic activation and the incidence of cumulus apoptosis in cumulus-oocyte complexes were observed as well. Oocytes exposed to different doses of Aroclor 1254 in vivo were associated with a significant decrease in outgrowth potential, abnormal spindle configurations, and the inhibition of parthenogenetic activation of ovulated oocytes. Furthermore, the incidence of apoptosis in cumulus cells was increased after exposed to Aroclor 1254. These results may provide reference for the treatment of reproductive diseases such as infertility or miscarriage caused by environmental contaminants.

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Apoptosis in bovine cumulus–oocyte complexes after exposure to polychlorinated biphenyl mixtures during in vitro maturation

Cited by 37 publications

References 51 publications

Regulation of aryl hydrocarbon receptor activity in porcine cumulus–oocyte complexes in physiological and toxicological conditions: the role of follicular fluid

Regulation of aryl hydrocarbon receptor activity in porcine cumulus–oocyte complexes in physiological and toxicological conditions: the role of follicular fluid

FSHR and LHR Expression and Signaling as Well as Maturation and Apoptosis of Cumulus-Oocyte Complexes Following Treatment with FSH Receptor Binding Inhibitor in Sheep

Effects of Aroclor 1254 on In Vivo Oocyte Maturation in the Mouse

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