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PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection.

PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort.

FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system.

FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.

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.

Background: More than two in five Swedish women are overweight or obese when becoming pregnant. Maternal overweight or obesity and excessive pregnancy weight gain are associated with several adverse pregnancy outcomes. The underlying mechanisms that link maternal adiposity, diet, exercise, pregnancy weight gain with pregnancy outcome are incompletely understood. Methods: We describe the design for a cross-sectional study of pregnant women at Uppsala University Hospital, Sweden. All participants delivered by elective cesarean section before the onset of labor. At inclusion, participants answered two questionnaires concerning their dietary and exercise habits. Fasting maternal blood samples (buffy coat, plasma, serum) were collected. During the cesarean section, biopsies of maternal subcutaneous and visceral adipose tissues were obtained. Placental tissue was collected after delivery. All biological samples were processed as soon as possible, frozen on dry ice, and stored at -70 degrees C. Pregnancy outcomes and supplementary maternal characteristics were collected from medical records. Results: In total, 143 women were included in the study. Of these women, 33.6% were primiparous, 46.2% had a pre-pregnancy body mass index (BMI) over 25 kg/m(2), and 11.2% of the offspring were born large for gestational age (LGA). Complete collection, that is both questionnaires and all types of biological samples, was obtained from 81.1% of the participants. Conclusions: This study is expected to provide a resource for exploration of the associations between maternal weight, diet, exercise, pregnancy weight gain, and pregnancy outcome. Results from this study will be published in peer-reviewed, international scientific journals. This study was approved by the Regional Ethics Review Board in Uppsala (approval no 2014/353) and with an amendment by the Swedish Ethical Review Authority (approval no 2020-05844).

Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While thesecompounds have been reported as reproductive toxicants, their effects may partially be attributedto metabolites. The aim of this study was to examine reproductive organ development in chickenembryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP;100 μg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 μg/g egg). The mixturewas designed within the EU project EDC-MixRisk based upon a negative association with anogenitaldistance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryoswere exposed in ovo from an initial stage of gonad differentiation (embryonic day 4) anddissected two days prior to anticipated hatching (embryonic day 19). No discernible effectswere noted on reproductive organs in embryos exposed to the mixture. MBP-treated malesexhibited retention of Müllerian ducts and feminization of the left testicle, while MBPadministeredfemales displayed a diminished the left ovary. In the left testicle of MBP-treatedmales, mRNA expression of female-associated genes was upregulated while the testicular markergene SOX9 was downregulated, corroborating a feminizing effect by MBP. Our results demonstratethat MBP, but not the phthalate monoester mixture, disrupts both male and femalereproductive organ development in an avian embryo model.

Exposure to metabolism disrupting compounds during development may have short- and long-term health consequences. We have studied the effects of a mixture that consists of perfluoroalkyl acids, phthalate monoesters, and triclosan (TCS) on metabolic endpoints in developing zebrafish (Danio rerio). The mixture has previously been negatively associated with birth weight in the Swedish pregnancy cohort SELMA. We also studied one of the mixture components (TCS) and the known obesogen tributyltin (TBT). Water concentrations of the mixture and TCS corresponded to 1, 20, 60, and 100 times the geometrical mean of the gestational week 10 serum concentration in the SELMA women. The fish were exposed from 3 hours post fertilization and effects on metabolic rate were assessed at 2-5 days post fertilization (dpf) and lipid content in the blood, whole-body neutral lipid content, and adiposity were determined at 7 dpf. Exposure to the mixture and TCS altered metabolic rate. The mixture and both single compounds reduced lipid levels in whole-body samples and in the blood. A higher proportion of fish in the mixture- and TBT-exposed groups had visible adipocytes at 7 dpf compared with the control group and a similar tendency was observed in TCS-exposed fish. Our results demonstrate metabolism disrupting properties of the mixture and its component TCS that were similar to those of TBT. The results further indicate that TCS contributes to, but is not solely responsible for, the effect by the mixture.

The plastic component bisphenol A (BPA) impairs reproductive organ development in various experimental animal species. In birds, effects are similar to those caused by other xenoestrogens. Because of its endocrine disrupting activity, BPA is being substituted with other bisphenols in many applications. Using the chicken embryo model, we explored whether the BPA alternatives bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) can induce effects on reproductive organ development similar to those induced by BPA. Embryos were exposed in ovo from embryonic day 4 (E4) to vehicle, BPAF at 2.1, 21, 210, and 520 nmol/g egg, or to BPA, BPF, or BPS at 210 nmol/g egg and were dissected on embryonic day 19. Similar to BPA, BPAF and BPF induced testis feminization, manifested as eg testis-size asymmetry and ovarian-like cortex in the left testis. In the BPS-group, too few males were alive on day 19 to evaluate any effects on testis development. We found no effects by any treatment on ovaries or Mullerian ducts. BPAF and BPS increased the gallbladder-somatic index and BPAF, BPF and BPS caused increased embryo mortality. The overall lowest-observed-adverse-effect level for BPAF was 210 nmol/g egg based on increased mortality, increased gallbladder-somatic index, and various signs of testis feminization. This study demonstrates that the BPA replacements BPAF, BPF, and BPS are embryotoxic and suggests that BPAF is at least as potent as BPA in inducing estrogen-like effects in chicken embryos. Our results support the notion that these bisphenols are not safe alternatives to BPA.

A wide variety of anthropogenic chemicals is detected in humans and wildlife and the health effects of various chemical exposures are not well understood. Early life stages are generally the most susceptible to chemical disruption and developmental exposure can cause disease in adulthood, but the mechanistic understanding of such effects is poor. Within the EU project EDC-MixRisk, a chemical mixture (Mixture G) was identified in the Swedish pregnancy cohort SELMA by the inverse association between levels in women at around gestational week ten with birth weight of their children. This mixture was composed of mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mono-isononyl phthalate, triclosan, perfluorohexane sulfonate, perfluorooctanoic acid, and perfluorooctane sulfonate. In a series of experimental studies, we characterized effects of Mixture G on early development in zebrafish models. Here, we studied apoptosis and Wnt/β-catenin signaling which are two evolutionarily conserved signaling pathways of crucial importance during development. We determined effects on apoptosis by measuring TUNEL staining, caspase-3 activity, and acridine orange staining in wildtype zebrafish embryos, while Wnt/β-catenin signaling was assayed using a transgenic line expressing an EGFP reporter at β-catenin-regulated promoters. We found that Mixture G increased apoptosis, suppressed Wnt/β-catenin signaling in the caudal fin, and altered the shape of the caudal fin at water concentrations only 20–100 times higher than the geometric mean serum concentration in the human cohort. These findings call for awareness that pollutant mixtures like mixture G may interfere with a variety of developmental processes, possibly resulting in adverse health effects.

Pregnancy is considered a pro-inflammatory state that requires physiologic adaptation of the immune system of the mother. The aim of the present study was to study inflammatory and hormonal changes during canine pregnancy. Studies included analyses of peripheral concentrations of the acute phase proteins fibrinogen and C-reactive protein (CRP), the hormones progesterone and insulin-like growth factor I (IGF-I), hemoglobin, and analyses of the total leukocyte numbers and expression of cell surface antigens. Twenty bitches were included in the present study; 12 pregnant bitches and eight nonpregnant control bitches that were followed during the corresponding phase of the oestrous cycle. Blood samples were collected at the day of optimal mating (day 0) and then on days 7, 14, 21, 28 and 42. Progesterone, IGF-I and CRP were analysed in serum and fibrinogen in EDTA plasma. Haematology and leukocyte expression of a panel of inflammation-associated adhesion molecules (CD 11a, CD 18 and CD 49d) were evaluated from EDTA blood. The data were analyzed as repeated-measures data, using a mixed model approach. Progesterone varied with time in both pregnant and control bitches, and IGF-I varied with time in pregnant bitches. Both fibrinogen and CRP increased significantly with time for the pregnant bitches, but no significant change was detected for the control bitches. Increases were seen from day 21. The hemoglobin concentration decreased significantly with time in both pregnant and non-pregnant bitches. The neutrophil and monocyte numbers increased significantly in pregnant but not in control bitches. Pregnancy induced increased granulocyte expression of cell surface marker CD 18, increased monocyte expression of CD 18 and CD 49d, and increased lymphocyte expression of CD 49d. In conclusion, we describe inflammatory changes during canine pregnancy that are manifested as increases in concentrations of CRP and fibrinogen, an increase in neutrophils and monocytes, and in activation of granulocytes, monocytes and lymphocytes. The changes should be taken into account when evaluating concentrations of APPS and WBC in bitches during pregnancy. A variation in IGF-I concentrations was detected during pregnancy.