| 1. |
- Abraham, Maria Celina, et al.
(författare)
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Breed influences on in vitro development of abattoir-derived bovine oocytes
- 2012
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a discrepancy in the reproductive performance between different cattle breeds. Using abattoir-derived ovaries and data base information we studied the effects of breed on in vitro fertilization and early embryo development. Methods: The in vitro developmental competence of oocytes from cattle (n = 202) of Swedish Red (SR), Swedish Holstein (SH) and mixed beef breeds was compared, retrospectively tracing donors of abattoir-derived ovaries using a combination of the national animal databases and abattoir information. Age was significantly lower and carcass conformation score was higher in the beef breeds than in the dairy breeds. Cumulus oocyte complexes (n = 1351) were aspirated from abattoir-derived ovaries from animals of known breed (visual inspection confirmed through databases), age (databases), and abattoir information. Oocytes were matured, fertilized (frozen semen from two dairy bulls) and cultured according to conventional protocols. On day 8, blastocysts were graded and the number of nuclei determined. Results: Cleavage rate was not different between the breeds but was significantly different between bulls. The percentage of blastocysts on day 8 was significantly higher when the oocyte donor's breed was beef or SR than SH. There was no significant difference in blastocyst grades or stages between the breeds, but the number of nuclei in day 8 blastocysts was significantly lower in SH compared to the beef. Conclusions: The use of abattoir-derived ovaries from animals whose background is traceable can be a valuable tool for research. Using this approach in the present study, oocyte donor breed was seen to affect early embryo development during in vitro embryo production, which may be a contributing factor to the declining fertility in some dairy breeds seen today.
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| 2. |
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| 3. |
- Al-Essawe, Essraa M, et al.
(författare)
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Seminal plasma influences the fertilizing potential of cryopreserved stallion sperm
- 2018
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Ingår i: Theriogenology. - : Elsevier BV. - 0093-691X .- 1879-3231. ; 115, s. 99-107
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Tidskriftsartikel (refereegranskat)abstract
- Seminal plasma (SP) contains proteins that may influence cryosurvival and prevent capacitation-like changes due to freezing and thawing. The objective of this study was to investigate the effect of adding pooled SP from "good" (GF) or "bad" (BF) freezer stallions on sperm cells' fertilizing ability. "Good freezers" refers to stallions that usually produce ejaculates which can withstand cryopreservation, whilst "bad freezer" stallions produce ejaculates which cannot tolerate the freezing process. A heterologous zona binding assay with in vitro matured bovine oocytes was used to assess the binding ability of equine sperm cells as a possible alternative to artificial insemination trials. The effect of adding SP i) prior to cryopreservation; ii) after thawing of sperm cells selected by single layer centrifugation (SLC); iii) to capacitation medium, was evaluated. Adding SP from GE stallions prior to cryopreservation reduced the mean number of sperm cells bound to the zona pellucida (ZP) compared to control (P = 0.0003), SP-free sperm cells and group received SP from BF stallions (P < 0.0001 for both). After thawing SLC-selected sperm cells treated with 5% SP showed a decrease in binding ability compared with SP-free sperm cells (P < 0.0001). The binding affinity of sperm cells was higher in the group treated with SP from GF than with SP from BF stallions (P < 0.05). Prolonged exposure to SP impaired the ability of stallion sperm cells to undergo capacitation and bind to ZP, regardless of the source of SP (P < 0.0001). The response of equine sperm cells to SP is influenced by the ability of the sperm cells to withstand cryopreservation and is affected by the timing of exposure and the origin of SP. Customization of the protocol for individual stallions is recommended to optimize the effect. (C) 2018 Elsevier Inc. All rights reserved.
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| 4. |
- Bellavia, Andrea, et al.
(författare)
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Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia
- 2023
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 216:Part 1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women of reproductive age are exposed to ubiquitous chemicals such as phthalates, parabens, and per -and polyfluoroalkyl substances (PFAS), which have potential endocrine disrupting properties and might affect fertility. Our objective was to investigate associations between potential endocrine-disrupting chemicals (EDCs) and female fertility in two cohorts of women attending fertility clinics.Methods: In a total population of 333 women in Sweden and Estonia, we studied the associations between chemicals and female fertility, evaluating ovarian sensitivity index (OSI) as an indicator of ovarian response, as well as clinical pregnancy and live birth from fresh and frozen embryo transfers. We measured 59 chemicals in follicular fluid samples and detected 3 phthalate metabolites, di-2-ethylhexyl phthalate (DEHP) metabolites, 1 paraben, and 6 PFAS in > 90% of the women. Associations were evaluated using multivariable-adjusted linear or logistic regression, categorizing EDCs into quartiles of their distributions, as well as with Bayesian Kernel Ma-chine Regression.Results: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, beta =-0.21, 95% CI:-0.38,-0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, beta =-0.22, 95% CI:-0.44,-0.01). Signals of potential associations were also observed at higher concentrations of PFUnDA in both the combined population (Q2 vs. Q1,beta =-0.16, 95% CI-0.31,-0.02) and the Estonian population (Q2 vs. Q1,beta =-0.27, 95% CI-0.45,-0.08), and for PFOA in the Estonian population (Q4 vs. Q1, beta =-0.31, 95% CI-0.61,-0.01). Associations of chemicals with clinical pregnancy and live birth presented wide confidence intervals.Conclusions: Within a large chemical mixture, we observed significant inverse associations levels of DEHP me-tabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.
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| 5. |
- Bjorvang, Richelle D., et al.
(författare)
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Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.
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| 6. |
- Brandt, Y., et al.
(författare)
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Effects of continuous elevated cortisol concentrations during oestrus on concentrations and patterns of progesterone, oestradiol and LH in the sow
- 2009
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Ingår i: Animal Reproduction Science. - : Elsevier Masson. - 0378-4320 .- 1873-2232. ; 110:1-2, s. 172-185
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effect of continuous elevated cortisol concentrations during standing oestrus on time of ovulation and patterns Of progesterone. oestradiol and luteinising, hormone (LH) in sows. The elevation of cortisol concentrations was achieved through repeated intravenous injections of synthetic adrenocorticotropic hormone (ACTH) every 2 It for approximately 48 h, from the onset of the second standing oestrus alter weaning. Treatment was terminated when ovulation was detected (monitored by transrectal ultrasonography every 4h) or when (lie sow had received a maximum of 24 injections. The close of ACTH (2.5 mu g/kg) was chosen to mimic the cortisol concentrations seen during mixing of unfamiliar SOWS. The sows (n = 14) Were surgically fitted with jugular vein catheters and randomly divided into a control (C group) where only NaCl solution were injected) or an ACTH group. Blood samples were collected every 2 h. In parallel with the blood sampling, saliva samples for cortisol analyses were taken from eight sows before onset of treatment and from four of the sows during treatment. There was no difference in time from onset of standing, oestrus to ovulation between the two groups. The interval between the peaks of oestradiol and LH to ovulation was prolonged in the ACTH group compared to the C group (p less than 0.05). with a tendency towards all earlier decline of oestradiol in the ACTH group. Cortisol and progesterone Concentrations were significantly elevated during treatment in the ACTH group (p less than 0.001). with cortisol peak concentrations occurring between 40 and 80 min after each ACTH injection. Cortisol concentrations in saliva and Plasma were highly correlated (p less than 0.001). In conclusion, elevated cortisol concentrations from the onset of standing oestrus increase progesterone concentrations and prolong the interval between oestradiol and LH peaks to ovulation, the latter possible due to an early decline in oestradiol concentrations and a change of the LH peak outline. the effect these hormonal changes have on reproductive performance need to be further investigated. (C) 2008 Elsevier B.V. All rights reserved.
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| 7. |
- Einarsson, Stig, et al.
(författare)
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A 25 years experience of group-housed sows-reproduction in animal welfare-friendly systems
- 2014
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 56
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Forskningsöversikt (refereegranskat)abstract
- Since January 1 2013, group housing of sows has been compulsory within the European Union (EU) in all pig holdings with more than ten sows. Sows and gilts need to be kept in groups from 4 weeks after service to 1 week before the expected time of farrowing (Article 3(4) of Directive 2008/120/EC on the protection of pigs). The legislation regarding group housing was adopted already in 2001 and a long transitional period was allowed to give member states and producers enough time for adaptation. Even so, group housing of sows still seems to be uncommon in the EU, and is also uncommon in commercial pig farming systems in the rest of the world. In this review we share our experience of the Swedish 25 years of animal welfare legislation stipulating that sows must be loose-housed which de facto means group housed. The two most important concerns related to reproductive function among group-housed sows are the occurrence of lactational oestrus when sows are group-housed during lactation, and the stress that is associated with group housing during mating and gestation. Field and clinical observations in non-lactating, group-housed sows in Sweden suggest that by making basic facts known about the pig reproductive physiology related to mating, we might achieve application of efficient batch-wise breeding without pharmacological interventions. Group housing of lactating sows has some production disadvantages and somewhat lower productivity would likely have to be expected. Recordings of behavioural indicators in different housing systems suggest a lower welfare level in stalled animals compared with group-housed ones. However, there are no consistent effects on the reproductive performance associated with different housing systems. Experimental studies suggest that the most sensitive period, regarding disturbance of reproductive functions by external stressors, is the time around oestrus. We conclude that by keeping sows according to the pig welfare-friendly Directive 2008/120/EC, it is possible to combine group-housing of sows with good reproductive performance and productivity. However, substantially increased research and development is needed to optimize these systems.
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| 8. |
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| 9. |
- Gonzalez Herrero, Raquel, et al.
(författare)
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Blood plasma collected after adrenocorticotropic hormone administration during the preovulatory period in the sow negatively affects in vitro fertilization by disturbing spermatozoa function
- 2015
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Ingår i: Theriogenology. - : Elsevier BV. - 0093-691X .- 1879-3231. ; 83, s. 1128-1139
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Tidskriftsartikel (refereegranskat)abstract
- Successful fertilization is essential for reproduction and might be negatively affected by stressful events, which could alter the environment where fertilization occurs. The aim of the study was to determine whether an altered hormonal profile in blood plasma caused by adrenocorticotropic hormone (ACTH) administration could affect in vitro fertilization in the pig model. In experiment 1, gametes were exposed for 24 hours to plasma from ACTHtreated, non-ACTH-treated sows, or medium with BSA. Fertilization, cleavage, and blastocyst rates were lower in the ACTH group compared with the no ACTH or BSA control groups (P < 0.01). In experiment 2, the exposure of matured oocytes for 1 hour before fertilization to the same treatments did not have an impact on their ability to undergo fertilization or on embryo development. In experiment 3, spermatozoa were incubated for 0, 1, 4, and 24 hours under the same conditions. There was no effect of treatment on sperm viability. The percentage of acrosome-reacted spermatozoa remained higher in the ACTH group compared with the non-ACTH-treated group through the incubation period (P < 0.001). Protein tyrosine phosphorylation (PTP) patterns were also affected by treatment (P < 0.001). The presence of an atypical PTP pattern was higher in the ACTH group at all the analyzed time points compared with the BSA and no ACTH groups (P < 0.001). In conclusion, this altered environment may not affect oocyte competence but might affect the sperm fertilizing ability through alterations in the acrosome reaction and correct sequence of PTP patterns. (C) 2015 Elsevier Inc. All rights reserved.
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| 10. |
- Gonzalez Herrero, Raquel, et al.
(författare)
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Characterization of Mitochondrial and Actin Patterns in Cat Oocytes and Blastocysts
- 2012
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Ingår i: Reproduction in Domestic Animals. - : Wiley. - 0936-6768 .- 1439-0531. ; 47, s. 118-120
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Tidskriftsartikel (refereegranskat)abstract
- Contents Actin microfilaments and mitochondria distribution are considered useful markers of cytoplasmic maturation, but no information is available regarding their distribution in cat oocytes and embryos. Thus, the purpose of this study was to (i) assess cytoplasmic characteristics of the oocyte by mitochondria and actin staining in immature and in vitro/in vivo matured cat oocytes and (ii) characterize mitochondria and actin distribution in in vitro produced blastocysts by confocal laser scanning microscopy. Additionally, in vivo matured oocytes were collected to assess mitochondria and actin. Transzonal cumulus cell projections were more abundant in immature oocytes than in matured oocytes. A relocation of mitochondria throughout meiosis was not clearly observed. However, most in vitro produced blastocysts were of good quality, according to their actin cytoskeleton integrity and mitochondria distribution. The functional significance of mitochondria distribution in cat oocytes in relation to their developmental competence requires further research. This study represents the original description of actin and mitochondrial patterns in cat oocytes and embryos.
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| 11. |
- Gonzalez Herrero, Raquel, et al.
(författare)
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Effect of an altered hormonal environment by blood plasma collected after adrenocorticotropic administration on embryo development and gene expression in porcine embryos
- 2021
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Ingår i: Theriogenology. - : Elsevier BV. - 0093-691X .- 1879-3231. ; 162, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- Early embryonic development may be affected by adrenal hyperactivity in stressful situations which may lead to endocrine changes in the embryo environment. A sensitive period in porcine embryo development is the 4-cell stage when the embryo genome activation occurs. A mixed in vivo-in vitro system was implemented to test whether an altered milieu around this stage could affect embryo development and blastocyst quality in the porcine model. After in vitro maturation and fertilisation, presumptive zygotes were exposed for 24 h to plasma collected after ovulation from adrenocorticotropic hormone (ACTH) treated, non-ACTH-treated sows; and, medium without plasma, supplemented with bovine serum albumin. Subsequently, embryo development and differences in gene expression were tested among treatments. Cleavage and blastocyst rates did not differ between treatments. Blastocyst quality by morphology assessment was similar when all the resulting blastocysts were included in the analysis. However, when only expanded blastocysts (and onwards) were included in the analysis, the blastocysts from the non-ACTH plasma group showed better quality score. Blastocyst quality by morphological assessment was not mirrored by the transcription levels of various important genes for embryo development whose gene expression profile did not significantly differ among groups. It is likely that the effect of the altered environment provided by plasma from ACTH-treated sows was too short to affect embryo development. Therefore, a brief exposure to an altered endocrine environment may not have harmful consequences for the embryo once fertilisation occurs. (c) 2021 The Authors. Published by Elsevier Inc.
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| 12. |
- Gonzalez Herrero, Raquel, et al.
(författare)
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Effect of blood plasma collected after adrenocorticotropic hormone administration during the preovulatory period in the sow on oocyte in vitro maturation
- 2013
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Ingår i: Theriogenology. - : Elsevier BV. - 0093-691X .- 1879-3231. ; 80, s. 673-683
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Tidskriftsartikel (refereegranskat)abstract
- Reproduction may be affected by stressful events changing the female endocrine or metabolic profile. An altered environment during oocyte development could influence the delicate process of oocyte maturation. Here, the effect of simulated stress by media supplementation with blood plasma from sows after adrenocorticotropic hormone (ACTH) administration during the preovulatory period was assessed. Oocytes were matured for 46 hours in the presence of plasma from ACTH-treated sows, or plasma from NaCl-treated control sows, or medium without plasma (BSA group). The plasma used had been collected at 36 and 12 hours (+/- 2 hours) before ovulation (for the first 24 hours + last 22 hours of maturation, respectively). Subsequent fertilization and embryo development were evaluated. Actin cytoskeleton and mitochondrial patterns were studied by confocal microscopy both in the oocytes and the resulting blastocysts. Nuclear maturation did not differ between treatments. Subtle differences were observed in the actin microfilaments in oocytes; however, mitochondrial patterns were associated with the treatment (P < 0.001). These differences in mitochondrial patterns were not reflected by in vitro outcomes, which were similar in all groups. In conclusion, an altered hormonal environment provided by a brief exposure to plasma from ACTH-treated sows during in vitro oocyte maturation could induce alterations in actin cytoskeleton and mitochondria( patterns in oocytes. However, these changes might not hamper the subsequent in vitro embryo development. (C) 2013 Elsevier Inc. All rights reserved.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Hallberg, Ida, et al.
(författare)
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Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment
- 2023
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Nature. - 1559-0631 .- 1559-064X. ; 33, s. 699-709
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Tidskriftsartikel (refereegranskat)abstract
- Background: Concerns have been raised whether exposure to endocrine-disrupting chemicals (EDCs) can alter reproductive functions and play a role in the aetiology of infertility in women. With increasing evidence of adverse effects, information on factors associated with exposure is necessary to form firm recommendations aiming at reducing exposure.Objective: Our aim was to identify associations between lifestyle factors including the home environment, use of personal care products (PCP), and dietary habits and concentrations of EDCs in ovarian follicular fluid.Methods: April-June 2016, 185 women undergoing ovum pick-up for in vitro fertilisation in Sweden were recruited. Correlation analyses were performed between self-reported lifestyle factors and concentration of EDCs analysed in follicular fluid. Habits related to cleaning, PCPs, and diet were assessed together with concentration of six per- and polyfluoroalkyl substances (PFASs) [PFHxS, PFOA, PFOS, PFNA, PFDA and PFUnDA], methyl paraben and eight phthalate metabolites [MECPP, MEHPP, MEOHP, MEHP, cxMinCH, cxMiNP, ohMiNP, MEP, MOHiBP]. Spearman's partial correlations were adjusted for age, parity and BMI.Results: Significant associations were discovered between multiple lifestyle factors and concentrations of EDCs in ovarian follicular fluid. After correcting p values for multiple testing, frequent use of perfume was associated with MEP (correlation rho = 0.41 (confidence interval 0.21-0.47), p < 0.001); hens' egg consumption was positively associated with PFOS (rho = 0.30 (0.15-0.43), p = 0.007) and PFUnDA (rho = 0.27 (0.12-0.40), p = 0.036). White fish consumption was positively associated with PFUnDA (rho = 0.34 (0.20-0.47), p < 0.001) and PFDA (rho = 0.27 (0.13-0.41), p = 0.028). More correlations were discovered when considering the raw uncorrected p values. Altogether, our results suggest that multiple lifestyle variables affect chemical contamination of follicular fluid.Impact statement: This study shows how lifestyle factors correlate with the level of contamination in the ovary by both persistent and semi-persistent chemicals in women of reproductive age. Subsequently, these data can be used to form recommendations regarding lifestyle to mitigate possible negative health outcomes and fertility problems associated with chemical exposure, and to inform chemical policy decision making. Our study can also help form the basis for the design of larger observational and intervention studies to examine possible effects of lifestyle changes on exposure levels, and to unravel the complex interactions between biological factors, lifestyle and chemical exposures in more detail.
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| 17. |
- Hallberg, Ida, et al.
(författare)
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Bovine oocyte exposure to perfluorohexane sulfonate (PFHxS) induces phenotypic, transcriptomic, and DNA methylation changes in resulting embryos in vitro
- 2022
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 109, s. 19-30
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge on the effects of perfluorohexane sulfonate (PFHxS) on ovarian function is limited. In the current study, we investigated the sensitivity of oocytes to PFHxS during in vitro maturation (IVM), including conse-quences on embryo development at the morphological, transcriptomic, and epigenomic levels. Bovine cumulus-oocyte complexes (COCs) were exposed to PFHxS during 22 h IVM. Following fertilisation, developmental competence was recorded until day 8 of culture. Two experiments were conducted: 1) exposure of COCs to 0.01 mu g mL(-1) -100 mu g mL(-1) PFHxS followed by confocal imaging to detect neutral lipids and nuclei, and 2) exposure of COCs to 0.1 mu g mL(-1) PFHxS followed by analysis of transcriptomic and DNA methylation changes in blastocysts. Decreased oocyte developmental competence was observed upon exposure to & nbsp;>= 40 mu g mL(-1) PFHxS and altered lipid distribution was observed in the blastocysts upon exposure to 1-10 mu g mL(-1) PFHxS (not observed at lower or higher concentrations). Transcriptomic data showed that genes affected by 0.1 mu g mL(-1) PFHxS were enriched for pathways related to increased synthesis and production of reactive oxygen species. Enrichment for peroxisome proliferator-activated receptor-gamma and oestrogen pathways was also observed. Genes linked to DNA methylation changes were enriched for similar pathways. In conclusion, exposure of the bovine oocyte to PFHxS during the narrow window of IVM affected subsequent embryonic development, as reflected by morphological and mo- lecular changes. This suggests that PFHxS interferes with the final nuclear and cytoplasmic maturation of the oocyte leading to decreased developmental competence to blastocyst stage.
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| 18. |
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| 19. |
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| 20. |
- Hallberg, Ida, et al.
(författare)
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Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation
- 2019
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 84, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids present in human tissues. In this study, effects on early embryo development after PFNA exposure were investigated using the bovine in vitro production system. Oocytes were exposed to PFNA during maturation in vitro (10 μg mL-1 and 0.1 μg mL-1), and then fertilized and cultured in parallel with control groups. Developmental parameters (cleavage, blastocyst formation) were followed and embryo quality evaluated (stage, grade). Embryos developed after exposure to 0.1 μg mL-1 were stained to distinguish nuclei, active mitochondria and neutral lipids. 10 μg mL-1 of PFNA had a severe negative effect on blastocyst formation (OR: 0.27 p < 0.05), an effect not observed at 0.1 μg mL-1. However, lipid droplet distribution was significantly altered in embryos exposed to 0.1 μg mL-1, suggesting a disturbance of lipid metabolism after exposure to sublethal levels of PFNA during oocyte maturation in vitro.
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| 21. |
- Hallberg, Ida, et al.
(författare)
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Perfluorooctane sulfonate (PFOS) exposure of bovine oocytes affects early embryonic development at human-relevant levels in an in vitro model
- 2021
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Ingår i: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 464
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctane sulfonate (PFOS) has been added to Stockholm Convention for global phase out, but will continue to contribute to the chemical burden in humans for a long time to come due to extreme persistence in the environment. In the body, PFOS is transferred into to the ovarian follicular fluid that surrounds the maturing oocyte. In the present study, bovine cumulus oocyte complexes were exposed to PFOS during 22 h in vitro maturation. Concentrations of 2 ng g(-1) (PFOS-02) representing average human exposure and 53 ng g(-1) (PFOS-53) relevant to highly exposed groups were used. After exposure, developmental competence was recorded until day 8 after fertilisation. Blastocysts were fixed and either stained to evaluate blastomere number and lipid distribution using confocal microscopy or frozen and pooled for microarray-based gene expression and DNA methylation analyses. PFOS-53 delayed the first cleavage to two-cell stage and beyond at 44 h after fertilisation (p < .01). No reduction of proportion blastocysts were seen at day 8 in either of the groups, but PFOS-53 exposure resulted in delayed development into more advanced stages of blastocysts seen as both reduced developmental stage (p = .001) and reduced number of blastomeres (p = .04). Blastocysts showed an altered lipid distribution that was more pronounced after exposure to PFOS-53 (increased total lipid volume, p=.0003, lipid volume/cell p < .0001) than PFOS-02, where only decreased average lipid droplet size (p=.02) was observed. Gene expression analyses revealed pathways differently regulated in the PFOS-treated groups compared to the controls, which were related to cell death and survival through e.g., P38 mitogen-activated protein kinases and signal transducer and activator of transcription 3, which in turn activates tumour protein 53 (TP53). Transcriptomic changes were also associated with metabolic stress response, differentiation and proliferation, which could help to explain the phenotypic changes seen in the blastocysts. The gene expression changes were more pronounced after exposure to PFOS-53 compared to PFOS-02. DNA-methylation changes were associated with similar biological functions as the transcriptomic data, with the most significantly associated pathway being TP53. Collectively, these results reveal that brief PFOS exposure during oocyte maturation alters the early embryo development at concentrations relevant to humans. This study adds to the evidence that PFOS has the potential to affect female fertility.
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| 22. |
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| 23. |
- Hallberg, Ida, et al.
(författare)
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Suspect and non-target screening of ovarian follicular fluid and serum : identification of anthropogenic chemicals and investigation of their association to fertility
- 2021
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Ingår i: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 23:10, s. 1578-1588
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Tidskriftsartikel (refereegranskat)abstract
- In this work, ultra-high performance liquid chromatography-high resolution (Orbitrap) mass spectrometry-based suspect and non-target screening was applied to follicular fluid (n = 161) and serum (n = 116) from women undergoing in vitro fertilization in order to identify substances that may be associated with decreased fertility. Detected features were prioritized for identification based on (i) hazard/exposure scores in a database of chemicals on the Swedish market and an in-house database on per- and polyfluoroalkyl substances (PFAS); (ii) enrichment in follicular fluid relative to serum; and (iii) association with treatment outcomes. Non-target screening detected 20 644 features in follicular fluid and 13 740 in serum. Two hundred and sixty-two features accumulated in follicular fluid (follicular fluid: serum ratio >20) and another 252 features were associated with embryo quality. Standards were used to confirm the identities of 21 compounds, including 11 PFAS. 6-Hydroxyindole was associated with lower embryo quality and 4-aminophenol was associated with higher embryo quality. Overall, we show the complexity of follicular fluid and the applicability of suspect and non-target screening for discovering both anthropogenic and endogenous substances, which may play a role in fertility in women.
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| 25. |
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