Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex

Acuña-Hernández, D.G.; Arreola-Mendoza, Laura; Santacruz-Márquez, Ramsés; García-Zepeda, Sihomara Patricia; Parra-Forero, Lyda Yuliana; Olivares-Reyes, J. Alberto; Hernández‐Ochoa, Isabel

doi:10.1016/j.taap.2018.02.011

Cited by 42 publications

(28 citation statements)

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“…In other studies in porcine and mouse COCs exposed to different EDs, it was found that they produce the inhibition of cumulus cell expansion, either accelerating the resumption of maturation due to damage in the cumulus cell‐oocyte communication or through the inhibition of oocyte maturation due to a disruption in the gap junctions (Acuña‐Hernández et al, 2018; Domínguez et al, 2016). Gap junctions between cumulus cells and oocytes are essential for the resumption of meiosis, where binding proteins such as connexins 43, 45 and 60 are essential in species such as pigs, so that any alterations may lead to the inhibition of maturation (Downs, 2001; Luciano et al, 2005; Tao et al, 2008; Zhou et al, 2016).…”

Section: Discussionmentioning

confidence: 96%

“…In addition, Jeong et al (2020) reported that BuPB decreased cumulus cell expansion at a concentration >300 μ m . Othertoxic agents such as perfluorinated compounds (Domínguez et al, 2016) and bisphenol A (Acuña‐Hernández et al, 2018) could inhibit gap junctions and damage granulosa cells, decreasing oocyte maturation whereby PBs could generate similar effects. Therefore, if cumulus cells are affected, IVM might be compromised.…”

Section: Discussionmentioning

confidence: 99%

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Effects of methylparaben on in vitro maturation of porcine oocytes

Barajas-Salinas

Ducolomb

Betancourt

et al. 2020

J of Applied Toxicology

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Parabens (PBs) are compounds widely used in industry for food and personal care products as antimicrobials and preservatives. Their indiscriminate use has resulted in their detection in different ecosystems so that humans and other organisms are highly exposed. Methylparaben (MePB), compared with other PBs, is mostly detected in food, personal care and baby care products. PBs could be linked to the generation of hormonal disorders and fertility impairment since their recent classification as endocrine disruptors. The knowledge of the effects that MePB can exert is of great importance as, in terms of reproduction, information is limited. Therefore, the objective of the present study was to evaluate the effect of MePB on porcine oocyte viability and in vitro maturation (IVM), as well as to determine the lethal concentration at 50% (LC 50) and the maturation inhibition concentration at 50% (MIC 50). Oocytes were exposed to different MePB concentrations 0 (control), 50, 100, 500, 750 and 1000 μM during 44 h of IVM. Cytoplasmic alterations and reduced cumulus cell expansion were observed in oocytes exposed to MePB; however, viability was not affected. In addition, oocyte maturation decreased in a concentration-dependent manner after exposure to MePB. The estimated LC 50 was 2028.38 μM, whereas MIC 50 was 780.31 μM. To our knowledge, this is the first study that demonstrates that MePB altered porcine oocyte morphology, and caused a reduction in cumulus cell expansion, both of which resulted in decreased oocyte maturation. Therefore, MePB exposure may be one of the factors involved in fertility impairment in mammals, including that of humans.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Effects of methylparaben on in vitro maturation of porcine oocytes

Barajas-Salinas

Ducolomb

Betancourt

et al. 2020

J of Applied Toxicology

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“…MAPK signaling pathway regulates the development of oocytes [30]. During the development of COCs, the gap junction pathway mediates material exchange between oocytes and CCs [31]. Downregulated genes enriched the estrogen signaling pathway and the RAP1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

The effect of lysophosphatidic acid-supplemented culture medium on human immature oocytes matured in vitro

Xie

Xing

et al. 2021

Reprod Biol Endocrinol

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Background Lysophosphatidic acid-supplemented culture medium significantly increases the oocyte maturation rate in vitro. However, potential targets and pathways involved remain unknown. Methods A total of 43 women, who underwent cesarean section and aged between 18 and 35 years with good health, were included in this study. Immature oocytes were obtained and cultured with 10 µM lysophosphatidic acid. After culture, oocyte maturation was assessed and oocytes and cumulus cells were collected for RNA sequencing. Hierarchical indexing for spliced alignment of transcripts 2 method was used to align clean reads to the human genome. The featureCounts and edgeR package were used to calculate gene expression and analyze differences between groups respectively. ClusterProfiler program was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Results Oocyte maturation rate increased significantly following 48 h culture with lysophosphatidic acid. In cumulus cells, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in TNF signaling and insulin secretion pathways and downregulated genes were enriched in TNF signaling and cell adhesion molecules. In oocytes, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in MAPK signaling, gap junction, and cell cycle pathways and downregulated genes were enriched in MAPK signaling, estrogen signaling, RAP1 signaling, and gap junction pathways. Conclusions Lysophosphatidic acid in culture medium enhances human oocyte maturation in vitro and the identified some potential pathways may associate with oocyte maturation.

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“…MAPK signaling pathway regulates the development of oocytes (38). During the development of COCs, the gap junction pathway mediates material exchange between oocytes and cumulus cells (39). Downregulated genes enriched the estrogen signaling pathway and the RAP1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Lysophosphatidic Acid-supplemented Culture Medium on Human Immature Oocytes Matured in Vitro

Xie

Xing

et al. 2021

Preprint

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Background: Lysophosphatidic acid-supplemented culture medium significantly increases the oocyte maturation rate in vitro. However, potential targets and pathways involved remain unknown.Methods: A total of 43 women, who underwent cesarean section and aged between 18-35 years with good health, were included in this study. Immature oocytes were obtained and cultured with 10 mM lysophosphatidic acid. After culture, oocyte maturation was assessed and oocytes and cumulus cells were collected for RNA sequencing. HISAT2 was used to align clean reads to the human genome. The featureCounts and edgeR package were used to calculate gene expression and analyze differences between groups respectively. ClusterProfiler program was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Results: Oocyte maturation rate increased significantly after 48 h treatment with lysophosphatidic acid. In cumulus cells, 259 genes were upregulated and 237 were downregulated in the treatment group; Gene Ontology analysis revealed that 653 biological process, 61 cellular component, and 86 molecular function items were enriched by upregulated genes; 379 biological process, 46 cellular component, and 97 molecular function items were enriched by downregulated genes; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in TNF signaling and insulin secretion pathways and downregulated genes were enriched in TNF signaling and cell adhesion molecules. In oocytes, 128 genes were upregulated and downregulated in the treatment group; Gene Ontology analysis revealed that 300 biological process items, 44 cellular component items, and 93 molecular function items were enriched by upregulated genes; 268 biological process items, 22 cellular component items, and 72 molecular function items were enriched by downregulated genes; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in MAPK signaling, gap junction, and cell cycle pathways and downregulated genes were enriched in MAPK signaling, estrogen signaling, RAP1 signaling, and gap junction pathways.Conclusions: Our study indicates that lysophosphatidic acid in culture medium enhances human oocyte maturation in vitro and identifies some potential targets and pathways associated with oocyte maturation for the first time and are important in clinical settings.

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Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex

Cited by 42 publications

References 56 publications

Effects of methylparaben on in vitro maturation of porcine oocytes

Effects of methylparaben on in vitro maturation of porcine oocytes

The effect of lysophosphatidic acid-supplemented culture medium on human immature oocytes matured in vitro

The Effect of Lysophosphatidic Acid-supplemented Culture Medium on Human Immature Oocytes Matured in Vitro

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