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- 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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| 2. |
- Bjorvang, Richelle D., et al.
(författare)
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Persistent organic pollutants, pre-pregnancy use of combined oral contraceptives, age, and time-to-pregnancy in the SELMA cohort
- 2020
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Ingår i: Environmental Health. - : BMC. - 1476-069X. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background We are exposed to several chemicals such as persistent organic pollutants (POPs) in our everyday lives. Prior evidence has suggested that POPs may have adverse effects on reproductive function by disrupting hormone synthesis and metabolism. While there is age-related decline of fertility, the use of hormonal combined oral contraceptives (COCs) and its association to return of fertility remains controversial. The goal of this study is to investigate the association between exposure to POPs, both individually and as a mixture, and fecundability measured as time-to-pregnancy (TTP) according to pre-pregnancy use of COCs and age. Methods Using the SELMA (Swedish Environmental Longitudinal Mother and Child, Allergy and Asthma) study, we have identified 818 pregnant women aged 18-43 years (mean 29 years) with data on how long they tried to get pregnant and what was their most recently used contraceptive method. These data were collected at enrollment to the study (median week 10 of pregnancy). Concentrations of 22 POPs and cotinine were analyzed in the blood samples collected at the same time as the questions on TTP and pre-pregnancy use of contraceptive. Analyses were done on the association between POPs exposure and TTP measured as continuous (months) and binary (infertile for those with TTP > 12 months). To study the chemicals individually, Cox regression and logistic regression were used to estimate fecundability ratios (FRs) and odds ratios (ORs), respectively. Weighted quantile sum (WQS) regression was used to investigate the chemicals as a mixture where chemicals of concern were identified above the 7.6% threshold of equal weights. To perform the subgroup analysis, we stratified the sample according to use of COCs as the most recent pre-pregnancy contraception method and age (< 29 years, and >= 29 years). The models were adjusted for parity, regularity of menses, maternal body mass index (BMI) and smoking status, and stratified as described above. Results Prior to stratification, none of the POPs were associated with fecundability while increased exposure to HCB, PCB 74 and 118 had higher odds of infertility. Upon stratification, POP exposure was significantly associated with longer TTP in women aged >= 29 years who did not use COC. Specifically, PCBs 156, 180, 183, and 187 were associated with reduced fecundability while PCBs 99, 153, 156, 180, 183, and 187 had higher odds of infertility. As a mixture, we identified the chemicals of concern for a longer TTP include PCBs 118, 156, 183, and 187. Moreover, chemicals of concern identified with increased odds of infertility were PCB 74, 156, 183, 187, and transnonachlor. Conclusion Serum concentrations of selected POPs, both as individual chemicals and as a mixture, were significantly associated with lower fecundability and increased odds of infertility in women aged 29 years and above not using COC as their most recent pre-pregnancy contraceptive. Our findings suggest that pre-pregnancy use of oral contraceptive and age may modify the link between POPs and fecundability. The differences of specific chemicals in the individual analysis and as a mixture support the need to study combination effects of chemicals when evaluating reproductive outcomes.
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| 3. |
- Lavogina, Darja, et al.
(författare)
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Endocrine disrupting chemicals interfere with decidualization of human primary endometrial stromal cells in vitro
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- 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 mu M 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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