Killing two birds with one stone: Pregnancy is a sensitive window for endocrine effects on both the mother and the fetus.

Pregnancy is a complex process requiring tremendous physiological changes in the mother in order to fulfill the needs of the growing fetus, and to give birth, expel the placenta and nurse the newborn. These physiological modifications are accompanied with psychological changes, as well as with variations in habits and behaviors. As a result, this period of life is considered as a sensitive window as impaired functional and physiological changes in the mother can have short- and long-term impacts on her health. In addition, dysregulation of the placenta and of mechanisms governing placentation have been linked to chronic diseases later-on in life for the fetus, in a concept known as the Developmental Origin of Health and Diseases (DOHaD). This concept stipulates that any change in the environment during the pre-conception and perinatal (in utero life and neonatal) period to puberty, can be "imprinted" in the organism, thereby impacting the health and risk of chronic diseases later in life. Pregnancy is a succession of events that is regulated, in large part, by hormones and growth factors. Therefore, small changes in hormonal balance can have important effects on both the mother and the developing fetus. An increasing number of studies demonstrate that exposure to endocrine disrupting compounds (EDCs) affect both the mother and the fetus giving rise to growing concerns surrounding these exposures. This review will give an overview of changes that happen during pregnancy with respect to the mother, the placenta, and the fetus, and of the current literature regarding the effects of EDCs during this specific sensitive window of exposure.

The Tampa Scale of Kinesiophobia: Structural Validation among Adolescents with Idiopathic Scoliosis Undergoing Spinal Fusion Surgery.

AIMS: Spinal fusion surgery is one of the most invasive orthopedic surgeries. Pain while moving or a fear of experiencing pain after surgery may delay return to function and cause prolonged disability. The purpose of the study was to examine the psychometric properties of the Tampa Scale of Kinesiophobia (TSK) in pediatric patients undergoing scoliosis surgery. METHODS: Fifty-five adolescents (10-18 years old) scheduled for spinal fusion surgery were enrolled. Participants completed the TSK questionnaire before surgery and six weeks after surgery. Reliability, exploratory and confirmatory factor analyses were performed on the two-factors TSK including activity avoidance (TSK-AA) and somatic focus (TSK-SF). RESULTS: Before and after surgery, all TSK-AA items conformed into the same factor component and revealed good internal reliability with Cronbach's alpha of .76 and .70 respectively. TSK-SF items were separated into different factor components and revealed poor reliability (.11 and .56). The TSK-AA also produced an adequate fit to the data, as reflected with several fit indices at both timepoints, respectively: χ2/df = 1.19 and 1.22; CFI=.96 and .94; and RMSEA=.06 and .06. CONCLUSIONS: The TSK-AA demonstrated good psychometric properties in patients undergoing scoliosis surgery, which provides empirical evidence for pediatrics. Its validation in distinct populations and settings is recommended prior to its use.

Di(2-ethylhexyl) phthalate (DEHP) increases proliferation of epithelial breast cancer cells through progesterone receptor dysregulation.

The di(2-ethylhexyl) phthalate (DEHP) is a plasticizer incorporated to plastic matrices of widely used consumer products. However, it is gradually released from these products, resulting in a chronic exposure for humans. Although DEHP, similar to other members of the phthalates family, is generally considered as an endocrine disruptor, the mechanisms implicated in its toxicity are yet poorly understood. Our objective was to determine the effects of an exposure to DEHP and to one of its major metabolite, the mono(2-ethylhexyl) phthalate (MEHP) on markers involved in breast carcinogenesis. T-47D cells were exposed to environmentally relevant and higher doses of DEHP and MEHP (0.1-10 000 nM) for 4 days. Our results showed that an exposure to 10 000 nM of DEHP and 0.1 nM of MEHP significantly increased the proliferation of T-47D cells, without inducing apoptosis. In addition, a significant increase in the protein levels of the isoform A of the progesterone receptor (PR) and of nuclear levels of PR were observed in T-47D cells exposed to 10 000 nM of DEHP. Importantly, the increased proliferation and nuclear levels of PR were totally and partially inhibited, respectively, by Mifepristone, a PR antagonist. These results suggest that an exposure to DEHP or MEHP increase cell proliferation by activating PR signaling, which could potentially increase the risks to develop breast cancer. The mechanism of activation of the progesterone pathway by DEHP and the long-term consequences of this activation remained to be elucidated.

Strategies included in cognitive behavioral therapy programs to treat internalized disorders: a systematic review.

This review aimed to identify the strategies used in programs based on cognitive behavioral therapy (CBT) to prevent and treat symptoms of anxiety, depression, and internalized behaviors of children and adolescents. Based on an online search (ERIC, PsycInfo, Virtuose UQAM, and Google Scholar), 61 studies describing different cognitive behavioral programs were selected. Results showed that 40 strategies were implemented in at least one program. However, none of the strategies were systematically present in all programs, and only few were reported in more than 50% of the studies. Cognitive restructuring and problem-solving were the most popular strategies to treat depressive symptoms, whereas anxiety programs also generally included relaxation and exposure. Furthermore, six strategies were identified in a single anxiety program, whereas nine strategies were implemented in only one depression program. These results suggest that in anxiety and depression programs designed for children and adolescents, the label "CBT" encompasses a wide variety of programs with only few similar strategies. Such findings highlight the need to define a common basis for CBT programs, in order to better reflect CBT theory and to identify the effectiveness of the strategies included in these programs.

The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer.

Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

Connexins, E-cadherin, Claudin-7 and ß-catenin transiently form junctional nexuses during the post-natal mammary gland development.

Gap junctions are intercellular channels made of connexins (Cxs) that allow direct communication between adjacent cells. Modulation of Cxs has been associated with abnormal development and function of the mammary gland and breast cancer. However, the mechanisms underlying their expression during normal mammary gland are not yet known. Cxs interact with components of tight and adherens junctions. Thus, we hypothesized that the expression levels of Cxs vary during mammary gland development and are regulated through stage-dependent interactions with members of the tight and adherens junctions. Our specific objectives were to: 1) determine the expression of Cxs and tight and adherens junction proteins throughout development and 2) characterize Cxs interactions with components of tight and adherens junctions. Murine mammary glands were sampled at various developmental stages (pre-pubescent to post-weaning). RT-qPCR and western-blot analyses demonstrated differential expression patterns for all gap (Cx43, Cx32, Cx26, Cx30), tight (Claudin-1, -3, -4, -7) and adherens (ß-catenin, E- and P-cadherins) junctions throughout development. Interestingly, co-immunoprecipitation demonstrated interactions between these different types of junctions. Cx30 interacted with Cx26 just at the late pregnancy stage. While Cx43 showed a persistent interaction with ß-catenin from virginity to post-weaning, its interactions with E-cadherin and Claudin-7 were transient. Cx32 interacted with Cx26, E-cadherin and ß-catenin during lactation. Immunofluorescence results confirmed the existence of a junctional nexus that remodeled during mammary gland development. Together, our results confirm that the expression levels of Cxs vary concomitantly and that Cxs form junctional nexuses with tight and adherens junctions, suggesting the existence of common regulatory pathways.

Chronic exposure to hexachlorobenzene results in down-regulation of connexin43 in the breast.

Decreased expression of connexins has been associated with cancer, but the underlying mechanisms are poorly understood. We have previously shown that a 5 day exposure to hexachlorobenzene (HCB) resulted in decreased connexins expression in hepatocytes 45 days later, and that this down-regulation was linked to activation of Akt through the ILK pathway. Because HCB promotes cancer in both the liver and breast, the present study aimed to determine if the mechanisms are similar in both tissues. MCF-12A breast cells were thus transfected with vectors coding for either Akt or a constitutively active form of Akt. In those cells, activation of Akt was correlated with decreased Cx43 levels. Female rats were then exposed to HCB by gavage either following the same protocol used previously for the liver or through a chronic exposure. While no changes were observed after the 5 days exposure protocol, chronic exposure to HCB resulted in increased Akt levels and decreased Cx43 levels in breast cells. In vitro, Akt was activated in MCF-12A cells exposed to HCB either for 7 days or chronically, but no changes were observed in junctional proteins. Together, these results suggested that, while activation of Akt can decrease Cx43 expression in breast cells in vitro, other mechanisms are involved during HCB exposure, leading to a decrease in Cx43 levels in a model- and duration-dependent manner. Finally, we showed that HCB effects are tissue specific, as we did not observe the same results in breast and liver tissues.

Acute stress contributes to individual differences in pain and pain-related brain activity in healthy and chronic pain patients.

Individual differences in pain sensitivity and reactivity are well recognized but the underlying mechanisms are likely to be diverse. The phenomenon of stress-induced analgesia is well documented in animal research and individual variability in the stress response in humans may produce corresponding changes in pain. We assessed the magnitude of the acute stress response of 16 chronic back pain (CBP) patients and 18 healthy individuals exposed to noxious thermal stimulations administered in a functional magnetic resonance imaging experiment and tested its possible contribution to individual differences in pain perception. The temperature of the noxious stimulations was determined individually to control for differences in pain sensitivity. The two groups showed similar significant increases in reactive cortisol across the scanning session when compared with their basal levels collected over 7 consecutive days, suggesting normal hypothalamic-pituitary-adrenal axis reactivity to painful stressors in CBP patients. Critically, after controlling for any effect of group and stimulus temperature, individuals with stronger cortisol responses reported less pain unpleasantness and showed reduced blood oxygenation level-dependent activation in nucleus accumbens at the stimulus onset and in the anterior mid-cingulate cortex (aMCC), the primary somatosensory cortex, and the posterior insula. Mediation analyses indicated that pain-related activity in the aMCC mediated the relationship between the reactive cortisol response and the pain unpleasantness. Psychophysiological interaction analysis further revealed that higher stress reactivity was associated with reduced functional connectivity between the aMCC and the brainstem. These findings suggest that acute stress modulates pain in humans and contributes to individual variability in pain affect and pain-related brain activity.

The stress model of chronic pain: evidence from basal cortisol and hippocampal structure and function in humans.

Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations administered in 16 patients with chronic back pain and 18 healthy control subjects. Results showed that patients with chronic back pain have higher levels of cortisol than control subjects. In these patients, higher cortisol was associated with smaller hippocampal volume and stronger pain-evoked activity in the anterior parahippocampal gyrus, a region involved in anticipatory anxiety and associative learning. Importantly, path modelling-a statistical approach used to examine the empirical validity of propositions grounded on previous literature-revealed that the cortisol levels and phasic pain responses in the parahippocampal gyrus mediated a negative association between the hippocampal volume and the chronic pain intensity. These findings support a stress model of chronic pain suggesting that the sustained endocrine stress response observed in individuals with a smaller hippocampii induces changes in the function of the hippocampal complex that may contribute to the persistent pain states.

Hormonal regulation of miRNA during mammary gland development.

The mammary gland is a unique organ as most of its development occurs after birth through stages of proliferation, differentiation and apoptosis that are tightly regulated by circulating hormones and growth factors. Throughout development, hormonal cues induce the regulation of different pathways, ultimately leading to differential transcription and expression of genes involved in this process, but also in the activation or inhibition of post-transcriptional mechanisms of regulation. However, the role of microRNAs (miRNAs) in the different phases of mammary gland remodeling is still poorly understood. The objectives of this study were to analyze the expression of miRNA in key stages of mammary gland development in mice and to determine whether it could be associated with hormonal variation between stages. To do so, miRNAs were isolated from mouse mammary glands at stages of adulthood, pregnancy, lactation and involution, and sequenced. Results showed that 490, 473, 419, and 460 miRNAs are detected in adult, pregnant, lactating and involuting mice, respectively, most of them being common to all four groups, and 58 unique to one stage. Most genes could be divided into six clusters of expression, including two encompassing the highest number of miRNA (clusters 1 and 3) and showing opposite profiles of expression, reaching a peak at adulthood and valley at lactation, or showing the lowest expression at adulthood and peaking at lactation. GO and KEGG analyses suggest that the miRNAs differentially expressed between stages influence the expression of targets associated with mammary gland homeostasis and hormone regulation. To further understand the links between miRNA expression and hormones involved in mammary gland development, miRNAs were then sequenced in breast cells exposed to estradiol, progesterone, prolactin and oxytocin. Four, 38, 24 and 66 miRNAs were associated with progesterone, estradiol, prolactin, and oxytocin exposure, respectively. Finally, when looking at miRNAs modulated by the hormones, differentially expressed during mammary gland development, and having a pattern of expression that could be correlated with the relative levels of hormones known to be found in vivo, 16 miRNAs were identified as likely regulated by circulating hormones. Overall, our study brings a better understanding of the regulation of miRNAs throughout mammary gland development and suggests that there is a relationship between their expression and the main hormones involved in mammary gland development. Future studies will examine this role more in detail.

It takes two: examining the dynamic nature of cooperative behavior in adolescents.

Cooperating with those around us is an important facet of functioning in modern-day society. Forming successful cooperative relationships requires trust, reciprocity, and other interpersonal skills that continue to develop during adolescence. This study examined the dynamic nature of how trust is formed and broken among 248 adolescents (Males = 110, M Age = 15.1 years) throughout an iterative cooperative task (i.e., the Trust Game) and the interindividual differences that alter the success of their relationships. In our study, adolescents from the same classroom were anonymously paired and played a 10-trial version of the Trust Game, which examines trust and reciprocity. We found that trust is formed in the first half of the game and decreases as the threat of defection nears in the last trial. As the game progressed, the relationship between trial number and investments on the subsequent trial was mediated by percent return (ab = -0.09, 95% CI = [-0.15, -0.02]). Importantly, this relationship was moderated by social skills (p = 0.003) and impulsivity (p = 0.001), such that increases in either were associated with decreased percent return and investments on future trials. Overall, we found that cooperation is an adaptive behavior which requires trust and reciprocity, and adolescents need to exhibit both of these behaviors to have fruitful interactions. These findings suggest that interventions to help students think about their partner's perspective and stress the longer-term nature of interactions with peers would foster successful cooperation in social situations.

Understanding boys' underrepresentation in private and enriched programmes during the transition to secondary school.

BACKGROUND: In the past decades, there has been a growing concern to understand why boys struggle in school. One of the turning points in students' educational trajectories likely to exacerbate boys' academic difficulties is students' enrolment in private or enriched school programmes, as boys are underrepresented in such programmes. METHOD: To better understand this gender imbalance, our research draws on a longitudinal design to examine whether grade 6 students' externalizing behaviours, school engagement and school grades in mathematics and language arts relate to secondary school programme attendance, among a sample size of 577 students (277 boys). RESULTS: Path analysis showed that only language arts grades predicted enrolment in private or selective public programmes and contributed to boys' underrepresentation in these programmes. CONCLUSIONS: Such findings have important implications for understanding boys' underachievement and low persistence in school as well as to guide interventions to promote gender and overall educational equity in school.

Exposure to an environmentally representative mixture of polybrominated diphenyl ethers (PBDEs) alters zebrafish neuromuscular development.

Polybrominated diphenyl ethers (PBDEs) are a prevalent group of brominated flame retardants (BFRs) added to several products such as electronics, plastics, and textiles to reduce their flammability. They are reported as endocrine disruptors and neurodevelopmental toxicants that can accumulate in human and wildlife tissues, thus making their ability to leach out of products into the environment a great cause for concern. In this study, zebrafish (Danio rerio) embryos and larvae were exposed to a wide concentration range (1.5, 15, 150 and 300 pM) of a PBDE mixture from one to six days post-fertilization (dpf). Hatching rates, mortality and general morphology were assessed during the exposure period. A delay in hatching was observed at the two highest PBDEs concentrations and mortality rate increased at 6 dpf. By 4 dpf, larvae exposed to 150 pM and 300 pM PBDEs developed an upcurved phenotype. Analysis of motor behavior at 6 dpf revealed that PBDE exposure acutely reduced locomotion. To further analyze these motor deficits, we assessed the neural network density and motor neuron and neuromuscular junctions (NMJ) development by immunostaining and imaging. Acetylated α-tubulin staining revealed a significant loss of neurons in a dose-dependent manner. Synaptic vesicle protein 2 (SV2) and ⍺-bungarotoxin (⍺-BTX) staining revealed a similar pattern, with a significant loss of SV2 and nicotinic acetylcholine receptors, thus preventing the colocalization of presynaptic neurons with postsynaptic neurons. Consistent with these results, the presence of cleaved caspase-3 and acridine orange positive cells showed increased cell death in zebrafish larvae exposed to PBDEs. Our results suggest that exposure to PBDEs leads to deficits in the zebrafish neuromuscular system through neuron death, inducing morphological and motor deficiencies throughout their development. They provide valuable insight into the neurotoxic effects of PBDEs, further highlighting the relevance of the zebrafish model in toxicological studies.

Accelerating whole-sample polarization-resolved second harmonic generation imaging in mammary gland tissue via generative adversarial networks.

Polarization second harmonic generation (P-SHG) imaging is a powerful technique for studying the structure and properties of biological and material samples. However, conventional whole-sample P-SHG imaging is time consuming and requires expensive equipment. This paper introduces a novel approach that significantly improves imaging resolution under conditions of reduced imaging time and resolution, utilizing enhanced super-resolution generative adversarial networks (ESRGAN) to upscale low-resolution images. We demonstrate that this innovative approach maintains high image quality and analytical accuracy, while reducing the imaging time by more than 95%. We also discuss the benefits of the proposed method for reducing laser-induced photodamage, lowering the cost of optical components, and increasing the accessibility and applicability of P-SHG imaging in various fields. Our work significantly advances whole-sample mammary gland P-SHG imaging and opens new possibilities for scientific discovery and innovation.

Learning to embrace one's stress: the selective effects of short videos on youth's stress mindsets.

BACKGROUND AND OBJECTIVES: Stress is not inherently negative. As youth will inevitably experience stress when facing the various challenges of adolescence, they can benefit from developing a stress-can-be-enhancing mindset rather than learning to fear their stress responses and avoid taking on challenges. We aimed to verify whether a rapid intervention improved stress mindsets and diminished perceived stress and anxiety sensitivity in adolescents. DESIGN AND METHODS: An online experimental design randomly exposed 233 Canadian youths aged 14-17 (83% female) to four videos of the Stress N' Go intervention (how to embrace stress) or to control condition videos (brain facts). Validated questionnaires assessing stress mindsets, perceived stress, and anxiety sensitivity were administered pre- and post-intervention, followed by open-ended questions. RESULTS: The intervention content successfully instilled a stress-can-be-enhancing mindset compared to the control condition. Although Bayes factor analyses showed no main differences in perceived stress or anxiety sensitivity between conditions, a thematic analysis revealed that the intervention helped participants to live better with their stress. CONCLUSIONS: Overall, these results suggest that our intervention can rapidly modify stress mindsets in youth. Future studies are needed to determine whether modifying stress mindsets is sufficient to alter anxiety sensitivity in certain adolescents and contexts.

Regulation of host gene expression by HIV-1 TAR microRNAs.

BACKGROUND: The transactivating response (TAR) element of human immunodeficiency virus type 1 (HIV-1) is the source of two functional microRNAs (miRNAs), miR-TAR-5p and miR-TAR-3p. The objective of this study was to characterize the post-transcriptional regulation of host messenger RNAs (mRNAs) relevant to HIV-1 pathogenesis by HIV-1 TAR miRNAs. RESULTS: We demonstrated that TAR miRNAs derived from HIV-1 can incorporate into host effector Argonaute protein complexes, which is required if these miRNAs are to regulate host mRNA expression. Bioinformatic predictions and reporter gene activity assays identified regulatory elements complementary and responsive to miR-TAR-5p and miR-TAR-3p in the 3' untranslated region (UTR) of several candidate genes involved in apoptosis and cell survival. These include Caspase 8, Aiolos, Ikaros and Nucleophosmin (NPM)/B23. Analyses of Jurkat cells that stably expressed HIV-1 TAR or contained a full-length latent HIV provirus suggested that HIV-1 TAR miRNAs could regulate the expression of genes in T cells that affect the balance between apoptosis and cell survival. CONCLUSIONS: HIV-1 TAR miRNAs may contribute to the replication cycle and pathogenesis of HIV-1, by regulating host genes involved in the intricate balance between apoptosis and infected cell, to induce conditions that promote HIV-1 propagation and survival.

Effects of a Participation in a Structured Writing Retreat on Doctoral Mental Health: An Experimental and Comprehensive Study.

Challenges faced by doctoral researchers led to a concerning "doctoral mental health crisis" within academia. Recognizing the pressing need to address mental health concerns, notably among doctoral students, the Quebec Ministry of Higher Education introduced the Higher Education Student Mental Health Action Plan 2021-2026. One potentially relevant intervention approach is the implementation of tailored structured writing retreats for graduate students. Aiming to measure and explain the effects of participating to a three-day writing retreat on doctoral mental health, this study followed an explanatory sequential mixed method, including an experimental design. One hundred doctoral researchers were randomly assigned to either the experimental group (n = 50) or the waitlist control trial group (n = 50). Both groups answered a questionnaire comprising validated scales and open-ended questions at different timepoints, separated by a two-week gap. Results reveal that writing retreats reduced doctoral researchers' psychological distress and improved their psychological, emotional, and social wellbeing. Among the multiple writing retreat aspects evaluated, only productivity experienced, as well as socialization/networking opportunities, acted as predictors for all doctoral mental health measures. Qualitative findings further supported the importance of perceived productivity and socialization/networking in promoting doctoral mental health. Recommendations are provided for fostering a supportive research work environment for doctoral researchers.

Environmental Exposure to Brominated Flame Retardants: Unraveling Endocrine and Mammary Gland Effects That May Increase Disease Risk.

Brominated flame retardants (BFR) are molecules added to consumer products to reduce fire hazards. They were banned in North America and Europe because of their persistence and biomagnification. However, BFR are still released in the environment due to continued use of products manufactured before restriction, and from waste and recycling processes of those products. As a result, they remain sources of chronic environmental and human exposure worldwide. BFR are well-characterized endocrine disruptors. They have been associated with a wide range of alterations in endocrine and reproductive systems both in humans and experimental models in vivo and in vitro. Paradoxically, the effects of BFR on mammary glands, whose development and carcinogenesis are mainly under hormonal dependency are poorly known. There is increasing weight of evidence that exposure to endocrine disruptors promotes breast cancer, especially if the exposure occurs during sensitivity windows. For the mammary gland, these windows include the perinatal life, puberty, and pregnancy, as important remodeling of the organ happens during those periods. The peak of exposure to BFRs happened during late 1990s and beginning of 2000s in most countries. Women who were pregnant at that time are reaching menopause while their daughters are 20-30 years old. It is thus important to better understand the effects of BFRs on mammary gland development and breast cancer to determine whether these women are more at risk. Thus, this review aims to propose a comprehensive review of data reporting the effects of exposure to BFR on female endocrine and reproductive systems, with a particular focus on mammary gland development and of a potential increased risk of breast cancer.

A critical path to producing high quality, reproducible data from quantitative western blot experiments.

Western blotting experiments were initially performed to detect a target protein in a complex biological sample and more recently, to measure relative protein abundance. Chemiluminescence coupled with film-based detection was traditionally the gold standard for western blotting but accurate and reproducible quantification has been a major challenge from this methodology. The development of sensitive, camera-based detection technologies coupled with an updated technical approach permits the production of reproducible, quantitative data. Fluorescence reagent and detection solutions are the latest innovation in western blotting but there remains questions and debate concerning their relative sensitivity and dynamic range versus chemiluminescence. A methodology to optimize and produce excellent, quantitative western blot results with rigorous data analysis from membranes probed with both fluorescent and chemiluminescent antibodies is described. The data reveal when and how to apply these detection methods to achieve reproducible data with a stepwise approach to data processing for quantitative analysis.

Gestational and Lactational Exposure to the Emergent Alternative Plasticizer 1,2-Cyclohexane Dicarboxylic Acid Diisononyl Ester (DINCH) Impairs Lipid Metabolism to a Greater Extent Than the Commonly Used Di(2-Ethylhexyl) Phthalate (DEHP) in the Adult Rat Mammary Gland.

Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the mammary gland. Over the past few years, DEHP has been partially replaced by 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) which also have potential endocrine disrupting properties. The goal of the present study is to understand the impact of a gestational and lactational exposure to DEHP and DINCH on mammary gland development using Sprague Dawley rats. Both plasticizers altered the adipocytes of the mammary gland fat pad of adult progeny, as demonstrated by a decrease in their size, folding of their membrane, and modulations of the lipid profiles. DEHP treatments decreased the expression of Rxrα and Scd1 at the low and high dose, respectively, but did not affect any of the other genes studied. DINCH modulation of lipid metabolism could be observed at puberty by a decreased expression of genes implicated in triglyceride synthesis, lipid transport, and lipolysis, but by an increased expression of genes of the ß-oxidation pathway and of genes involved in lipid storage and fatty acid synthesis at adulthood, compared with control and DEHP-treated rats. A strong upregulation of different inflammatory markers was observed following DINCH exposure only. Together, our results indicate that a gestational and lactational exposure to DINCH has earlier and more significant effects on lipid homeostasis, adipogenesis, and the inflammatory state of the adult mammary gland than DEHP exposure. The long-term consequence of these effects on mammary gland health remained to be determined.