Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation

Hallberg, Ida; Kjellgren, Jacklin; Persson, Sara; Örn, Stefan

doi:10.1016/j.reprotox.2018.11.005

Cited by 25 publications

(22 citation statements)

References 58 publications

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“…folliculogenesis and steroidogenesis. PFAS exposure may alter follicle and oocyte development and diminish ovarian reserve ( Bellingham et al , 2009 ; Feng et al , 2015 , 2017 ; Domínguez et al , 2016 ; Chen et al , 2017 ; Du et al , 2019 ; Hallberg et al , 2019 ; López-Arellano et al , 2019 ). Potential mechanisms include PPAR activation, disruption of gap junction intercellular communication, oxidative stress and thyroid hormone disruption.…”

Section: Discussionmentioning

confidence: 99%

“…PFAS exposure has been shown to disrupt the earliest stage of folliculogenesis by altering oocyte development ( Domínguez et al , 2016 ; Hallberg et al , 2019 ; López-Arellano et al , 2019 ). The potential mechanisms include activation of peroxisome proliferator-activated receptor (PPAR) signalling pathways, disruption of intercellular communication between oocytes and granulosa cells and induction of oxidative stress.…”

Section: Mechanistic Evidence For Ovarian Toxicity Of Pfasmentioning

confidence: 99%

“…A recent study reported that administration of 10 μg/mL PFNA on bovine oocytes in vitro for 22 h has a negative effect on oocyte developmental competence during their maturation ( Hallberg et al , 2019 ). This decrease in oocyte survival was attributed to PPAR-α( Hallberg et al , 2019 ), leading to the disturbance of lipid metabolism and increased lipid accumulation in the ovaries ( Bjork and Wallace, 2009 ; Wang et al , 2012 ). Lending further support, another study showed that excessive lipids in the ooplasm correlated with impaired oocyte developmental competence and low oocyte survival rates ( Prates et al , 2014 ).…”

Section: Mechanistic Evidence For Ovarian Toxicity Of Pfasmentioning

confidence: 99%

“…Experimental studies have shown that PFAS exposure is associated with the depletion of ovarian reserve (i.e. the number of ovarian follicles and oocytes) ( Bellingham et al , 2009 ; Domínguez et al , 2016 ; Feng et al , 2015 , 2017 ; Chen et al , 2017 ; Du et al , 2019 ; Hallberg et al , 2019 ; López-Arellano et al , 2019 ) and inhibition steroidogenic enzyme activities ( Shi et al , 2009 ; Chaparro-Ortega et al , 2018 ; Wang et al ., 2018a ). Disruption of this finely controlled network may have physiologic impacts beyond the reproductive system, affecting the overall health of girls and women.…”

Section: Introductionmentioning

confidence: 99%

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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

Ding

Harlow

Randolph

et al. 2020

Human Reproduction Update

212

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BACKGROUND Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. Experimental models and epidemiologic studies suggest that PFAS exposures target the ovary and represent major risks for women’s health. OBJECTIVE AND RATIONALE This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function. SEARCH METHODS A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords (e.g. ovarian, reproductive, follicle, oocyte) to specific keywords (including menarche, menstrual cycle, menopause, primary ovarian insufficiency/premature ovarian failure, steroid hormones), based on the authors’ knowledge of the topic and key terms. OUTCOMES Clinical evidence demonstrates the presence of PFAS in follicular fluid and their ability to pass through the blood–follicle barrier. Although some studies found no evidence associating PFAS exposure with disruption in ovarian function, numerous epidemiologic studies, mostly with cross-sectional study designs, have identified associations of higher PFAS exposure with later menarche, irregular menstrual cycles, longer cycle length, earlier age of menopause and reduced levels of oestrogens and androgens. Adverse effects of PFAS on ovarian folliculogenesis and steroidogenesis have been confirmed in experimental models. Based on laboratory research findings, PFAS could diminish ovarian reserve and reduce endogenous hormone synthesis through activating peroxisome proliferator-activated receptors, disrupting gap junction intercellular communication between oocyte and granulosa cells, inducing thyroid hormone deficiency, antagonising ovarian enzyme activities involved in ovarian steroidogenesis or inhibiting kisspeptin signalling in the hypothalamus. WIDER IMPLICATIONS The published literature supports associations between PFAS exposure and adverse reproductive outcomes; however, the evidence remains insufficient to infer a causal relationship between PFAS exposure and ovarian disorders. Thus, more research is warranted. PFAS are of significant concern because these chemicals are ubiquitous and persistent in the environment and in humans. Moreover, susceptible groups, such as foetuses and pregnant women, may be exposed to harmful combinations of chemicals that include PFAS. However, the role environmental exposures play in reproductive disorders has received little attention by the medical community. To better understand the potential risk of PFAS on human ovarian function, additional experimental studies using PFAS doses equivalent to the exposure levels found in the general human population and mixtures of compounds are required. Prospective investigations in human populations are also warranted to ensure the temporality of PFAS exposure and health endpoints and to minimise the possibility of reverse causality.

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Section: Discussionmentioning

confidence: 99%

Section: Mechanistic Evidence For Ovarian Toxicity Of Pfasmentioning

confidence: 99%

Section: Mechanistic Evidence For Ovarian Toxicity Of Pfasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

Ding

Harlow

Randolph

et al. 2020

Human Reproduction Update

212

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“…In addition, PFNA may cause cytotoxicity in JEG-3 cells, PC12 cells, and lung cells in vitro [18,24,25]. Furthermore, PFNA causes developmental toxicity by impairing bovine embryo growth in vitro [26]. All the aforementioned studies suggest that PFNA exerts toxic effects both in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 99%

Perfluorononanoic acid impedes mouse oocyte maturation by inducing mitochondrial dysfunction and oxidative stress

Jiao

Liu

et al. 2021

Preprint

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Perfluorononanoic acid (PFNA), a member of PFAS, is frequently detected in human blood and tissues, even in follicular fluid of women. The exposure of PFNA, but not PFOA and PFOS, is positively correlated with miscarriage and increased time to pregnancy. Toxicological studies indicated that PFNA exposure is associated with immunotoxicity, hepatotoxicity, developmental toxicity, and reproductive toxicity in animals. However, there is little information regarding the toxic effects of PFNA on oocyte maturation. In this study, we investigated the toxic effects of PFNA exposure on mouse oocyte maturation in vitro. Our results showed that 600 μM PFNA significantly inhibited germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Our further study revealed that PFNA induced abnormal metaphase I (MI) spindle assembly, evidenced by malformed spindles and mislocalization of p-ERK1/2 in PFNA-treated oocytes. We also found that PFNA induced abnormal mitochondrial distribution and increased mitochondrial membrane potential. Consequently, PFNA increased reactive oxygen species (ROS) levels, leading to oxidative stress, DNA damage, and eventually early-stage apoptosis in oocytes. In addition, after 14 h culture, PFNA disrupted the formation of metaphase II (MII) spindle in most PFNA-treated oocytes with polar bodies. Collectively, our results indicate that PFNA interferes with oocyte maturation in vitro via disrupting spindle assembly, damaging mitochondrial functions, and inducing oxidative stress, DNA damage, and early-stage apoptosis.

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The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

Land

Miller

Fugate

et al. 2022

Molecular Reproduction Devel

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Exposure to endocrine‐disrupting chemicals (EDCs) is unavoidable, which represents a public health concern given the ability of EDCs to target the ovary. However, there is a large gap in the knowledge about the impact of EDCs on ovarian function, including the process of ovulation. Defects in ovulation are the leading cause of infertility in women, and EDC exposures are contributing to the prevalence of infertility. Thus, investigating the effects of EDCs on the ovary and ovulation is an emerging area for research and is the focus of this review. The effects of EDCs on gametogenesis, uterine function, embryonic development, and other aspects of fertility are not addressed to focus on ovarian‐ and ovulation‐related fertility issues. Herein, findings from epidemiological and basic science studies are summarized for several EDCs, including phthalates, bisphenols, per‐ and poly‐fluoroalkyl substances, flame retardants, parabens, and triclosan. Epidemiological literature suggests that exposure is associated with impaired fecundity and in vitro fertilization outcomes (decreased egg yield, pregnancies, and births), while basic science literature reports altered ovarian follicle and corpora lutea numbers, altered hormone levels, and impaired ovulatory processes. Future directions include identification of the mechanisms by which EDCs disrupt ovulation leading to infertility, especially in women.

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Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation

Cited by 25 publications

References 58 publications

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

Perfluorononanoic acid impedes mouse oocyte maturation by inducing mitochondrial dysfunction and oxidative stress

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

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