Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies

Björvang, Richelle D.; Hallberg, Ida; Pikki, Anne; Berglund, Lars; Pedrelli, Matteo; Kiviranta, Hannu; Rantakokko, Panu; Ruokojärvi, Päivi; Lindh, Christian; Olovsson, Matts; Persson, S. G. B.; Holte, Jan; Sjunnesson, Ylva; Damdimopoulou, Pauliina

doi:10.1016/j.envres.2021.112626

Cited by 29 publications

(26 citation statements)

References 46 publications

(50 reference statements)

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“…Apart from assessing PRL secretion and activity of PKA, we explored activity of Rho-dependent protein kinase (ROCK), protein kinase B (Akt/PKB), casein kinase 2 (CK2) and total protein concentration in lysates. The nine EDCs were chosen for the following reasons: BPA and its replacement chemical bisphenol F (BPF) because they have been studied in similar models before (Table 1) and BPA is a known human endocrine disrupter (European Chemicals Agency); phthalate MEHP (metabolite of DEHP) because it is also a known human endocrine disrupter (European Chemicals Agency) and associated to miscarriage in humans (18,20); organochlorine pesticides p,p'-DDE (metabolite of DDT) and HCB, and the polychlorinated biphenyls PCB180 and PCB170, because they associate to longer time-to-pregnancy in our cohort studies (35,36); HCB is also associated with lower odds for clinical pregnancy and live birth (36); and PFOS and perfluorooctanoic acid (PFOA) because they are associated to preterm birth, fetal growth restriction and preeclampsia in humans (19). In addition, the chosen EDCs have different physiochemical properties.…”

Section: Introductionsupporting

confidence: 62%

Endocrine disrupting chemicals interfere with decidualization of human primary endometrial stromal cells in vitro

et al. 2022

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Multiple studies have shown associations between exposure to endocrine disrupting chemicals (EDCs) and reduced fertility in women. However, little is known about the target organs of chemical disruption of female fertility. Here, we focus on the hormone-sensitive uterine lining, the endometrium, as a potential target. Decidualization is the morphological and functional change that endometrial stromal cells undergo to support endometrial receptivity, which is crucial for successful implantation, placentation, and pregnancy. We investigated the effect of nine selected EDCs on primary human endometrial stromal cell decidualization in vitro. The cells were exposed to a decidualization-inducing mixture in the presence or absence of 1 μM of nine different EDCs for nine days. Extent of decidualization was assessed by measuring the activity of cAMP dependent protein kinase, Rho-associated coiled-coil containing protein kinase, and protein kinase B in lysates using photoluminescent probes, and secretion of prolactin into the media by using ELISA. Decidualization-inducing mixture upregulated activity of protein kinases and prolactin secretion in cells derived from all women. Of the tested chemicals, dichlorodiphenyldichloroethylene (p,p’-DDE), hexachlorobenzene (HCB) and perfluorooctanesulfonic acid (PFOS) significantly reduced decidualization as judged by the kinase markers and prolactin secretion. In addition, bisphenol A (BPA) reduced prolactin secretion but did not significantly affect activity of the kinases. None of the EDCs was cytotoxic, based on the assessment of total protein content or activity of the viability marker casein kinase 2 in lysates. These results indicate that EDCs commonly present in the blood circulation of reproductive-aged women can reduce decidualization of human endometrial stromal cells in vitro. Future studies should focus on detailed hazard assessment to define possible risks of EDC exposure to endometrial dysfunction and implantation failure in women.

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Section: Introductionsupporting

confidence: 62%

Endocrine disrupting chemicals interfere with decidualization of human primary endometrial stromal cells in vitro

et al. 2022

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“…The concentrations used in this study exceed the levels detected in the average human population. Blood levels of PFASs correlate well with levels in follicular fluid of women [ 12 ] and can therefore be used as a proxy for oocyte exposure. Blood levels of PFASs in humans vary depending on compound and geographic region [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Inhalation of particles and direct contact are also known routes of exposure [7][8][9]. PFASs can be detected in blood of the general population worldwide [10][11][12], as well as in foetuses [13] and in ovarian follicular fluid [14]. Blood concentrations of PFASs in residents of heavily contaminated areas, and individuals subjected to occupational exposure, have been found to be substantially higher than in the general population [15,16].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of late-apoptotic symptoms in porcine preimplantation embryos upon exposure of oocytes to perfluoroalkyl substances (PFASs) under in vitro meiotic maturation

Leclercq

Hallberg

2022

PLoS ONE

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The objectives of this study were to evaluate the effect of perfluoroalkyl substances on early embryonic development and apoptosis in blastocysts using a porcine in vitro model. Porcine oocytes (N = 855) collected from abattoir ovaries were subjected to perfluorooctane sulfonic acid (PFOS) (0.1 μg/ml) and perfluorohexane sulfonic acid (PFHxS) (40 μg/ml) during in vitro maturation (IVM) for 45 h. The gametes were then fertilized and cultured in vitro, and developmental parameters were recorded. After 6 days of culture, resulting blastocysts (N = 146) were stained using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and imaged as stacks using confocal laser scanning microscopy. Proportion of apoptotic cells as well as total numbers of nuclei in each blastocyst were analyzed using objective image analysis. The experiment was run in 9 replicates, always with a control present. Effects on developmental parameters were analyzed using logistic regression, and effects on apoptosis and total numbers of nuclei were analyzed using linear regression. Higher cell count was associated with lower proportion of apoptotic cells, i.e., larger blastocysts contained less apoptotic cells. Upon PFAS exposure during IVM, PFHxS tended to result in higher blastocyst rates on day 5 post fertilization (p = 0.07) and on day 6 post fertilization (p = 0.05) as well as in higher apoptosis rates in blastocysts (p = 0.06). PFHxS resulted in higher total cell counts in blastocysts (p = 0.002). No effects attributable to the concentration of PFOS used here was seen. These findings add to the evidence that some perfluoroalkyl substances may affect female reproduction. More studies are needed to better understand potential implications for continued development as well as for human health.

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“…However, most scholars believe that this is related to the increased multiple pregnancy rate of ART and its own factors such as parents' age, body size, mental health, and disease, rather than the ART technology itself. Most studies have concluded that ART is safe, and ART offspring do not have an increased risk of adverse health compared with offspring born to natural pregnancies [ 8 ]. However, a growing number of studies have indicated that even when multiple births are ruled out, the poor health risk of singleton births in ART kids is still elevated.…”

Section: Introductionmentioning

confidence: 99%

Effect Analysis of Degranulated Cell in Early Fertilization on FET Outcome and Offspring Safety with Data Mining

Zhao

Li-ling

et al. 2022

Computational and Mathematical Methods in Medicine

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In vitro fertilization and embryo transfer is one type of assisted reproductive technology, although the technology is now more mature. Many factors, however, will have an impact on oocyte fertilization, embryo growth, pregnancy outcome, and child safety due to the journey from clinical to the laboratory. The influence of degranulated cells early in fertilization on frozen embryo transfer (FET) results is investigated in this study. This article analyzes 255 patients who underwent in vitro fertilization (IVF) and FET transplantation at the author’s central unit from January 1, 2015, to June 30, 2021. Among them, IVF-assisted conception is the early degranulation of homologous oocyte fertilization. Correlation analysis is performed by observing the embryonic outcome of the early degranulation group and the overnight fertilization group and the clinical outcome after FET. Through data mining analysis, the results show that the polyfertilization rate and 0PN rate for the early degranulation group are significantly higher than the overnight fertilization group (9.87% vs. 8.24% and 3.14% vs. 1.69%). In terms of normal fertilization rate, there is no significant difference between D3 high-quality embryo rate and D5 high-quality blastocyst rate (64.07% vs. 65.15%, 27.5% vs. 26.5%, and 15.97% vs. 17.35%). There is no significant difference in the complete recovery rate of embryos after thawing (93.24% vs. 93.46%), and the implantation rate, clinical pregnancy rate, abortion rate, and live birth rate are not significantly different between the two groups after FET. The offspring outcomes of singletons do not differ significantly between the two groups; however, twins born early degranulate have much greater rates of ultralow birth weight and ultrapreterm children than twins born overnight fertilization (14.29% vs. 0). Therefore, it can be concluded that degranulation of cells early in fertilization is a desirable method to prevent fertilization disorders. However, under the premise of ensuring that no fertilization disorder occurs, it is not appropriate to degranulate all the oocytes of the patient at the early stage of fertilization.

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Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies

Cited by 29 publications

References 46 publications

Endocrine disrupting chemicals interfere with decidualization of human primary endometrial stromal cells in vitro

Endocrine disrupting chemicals interfere with decidualization of human primary endometrial stromal cells in vitro

Occurrence of late-apoptotic symptoms in porcine preimplantation embryos upon exposure of oocytes to perfluoroalkyl substances (PFASs) under in vitro meiotic maturation

Effect Analysis of Degranulated Cell in Early Fertilization on FET Outcome and Offspring Safety with Data Mining

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