In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice

Background: Mosaicism, the presence of genetically distinct cell populations within an organism, has emerged as an important contributor to disease. Mutational events occurring during embryonic development can cause mosaicism in any tissue, but the influence of environmental factors on levels of mosaicism is unclear. Objectives: We investigated whether in utero exposure to the widespread environmental mutagen benzo[a]pyrene (BaP) has an impact on the burden and distribution of mutations in adult mice. Methods: We used the Muta™Mouse transgenic rodent model to quantify and characterize mutations in the offspring of pregnant mice exposed to BaP during postconception days 7 through 16, covering the major period of organogenesis in mice. Next-generation DNA sequencing was then used to determine the spectrum of mutations induced in adult mice that were exposed to BaP during fetal development. Results: Mutation frequency was significantly increased in the bone marrow, liver, brain, and sperm of first filial generation (F1) males. Developing embryos accumulated more mutations and exhibited higher proportions of mosaicism than exposed adults, particularly in the brain. Decreased sperm count and motility revealed additional negative impacts on the reproductive function of F1 males. Conclusion: In utero exposure to environmental mutagens contributes to somatic and germline mosaicism, permanently affecting both the genetic health of the F1 and the population gene pool. Citation: Meier MJ, O’Brien JM, Beal MA, Allan B, Yauk CL, Marchetti F. 2017. In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice

An ethnographic investigation of maternity healthcare experience of immigrants in rural and urban Alberta, Canada

Background: Canada is among the top immigrant-receiving nations in the world. Immigrant populations may face structural and individual barriers in the access to and navigation of healthcare services in a new country. The aims of the study were to (1) generate new understanding of the processes that perpetuate immigrant disadvantages in maternity healthcare, and (2) devise potential interventions that might improve maternity experiences and outcomes for immigrant women in Canada. Methods: The study utilized a qualitative research approach that focused on ethnographic research design and data analysis contextualized within theories of organizational behaviour and critical realism. Data were collected over 2.5 years using focus groups and in-depth semistructured interviews with immigrant women (n = 34), healthcare providers (n = 29), and social service providers (n = 23) in a Canadian province. Purposive samples of each subgroup were generated, and recruitment and data collection – including interpretation and verification of translations – were facilitated through the hiring of community researchers and collaborations with key informants. Results: The findings indicate that (a) communication difficulties, (b) lack of information, (c) lack of social support (isolation), (d) cultural beliefs, e) inadequate healthcare services, and (f) cost of medicine/services represent potential barriers to the access to and navigation of maternity services by immigrant women in Canada. Having successfully accessed and navigated services, immigrant women often face additional challenges that influence their level of satisfaction and quality of care, such as lack of understanding of the informed consent process, lack of regard by professionals for confidential patient information, short consultation times, short hospital stays, perceived discrimination/stereotyping, and culture shock. Conclusions: Although health service organizations and policies strive for universality and equality in service provision, personal and organizational barriers can limit care access, adequacy, and acceptability for immigrant women. A holistic healthcare approach must include health informational packages available in different languages/media. Health care professionals who care for diverse populations must be provided with training in cultural competence, and monitoring and evaluation programs to ameliorate personal and systemic discrimination

Characterization of Detailed Sedentary Postures Using a Tri-Monitor ActivPAL Configuration in Free-Living Conditions

Objective monitors such as the activPAL characterize time when the thigh is horizontal as sedentary time. However, there are physiological differences between lying, bent-legged sitting, and straight-legged sitting. We introduce a three-monitor configuration to assess detailed sedentary postures and demonstrate its use in characterizing such positions in free-living conditions. We explored time spent in each sedentary posture between prolonged (>1 h) versus non-prolonged (p p p > 0.26). We document that a considerable amount of waking time is accumulated in lying or straight-legged sitting. This methodological approach equips researchers with a means of characterizing detailed sedentary postures in uncontrolled conditions and may help answer novel research questions on sedentariness

Failure of spermatogenesis in mouse lines deficient in the Na(+)-K(+)-2Cl(–) cotransporter

The Na(+)-K(+)-2Cl(–) cotransporter (NKCC1) carries 1 molecule of Na(+) and K(+) along with 2 molecules of Cl(–) across the cell membrane. It is expressed in a broad spectrum of tissues and has been implicated in cell volume regulation and in ion transport by secretory epithelial tissue. However, the specific contribution of NKCC1 to the physiology of the various organ systems is largely undefined. We have generated mouse lines carrying either of 2 mutant alleles of the Slc12a2 gene, which encodes this cotransporter: a null allele and a mutation that results in deletion of 72 amino acids of the cytoplasmic domain. Both NKCC1-deficient mouse lines show behavioral abnormalities characteristic of mice with inner ear defects. Male NKCC1-deficient mice are infertile because of defective spermatogenesis, as shown by the absence of spermatozoa in histological sections of their epididymides and the small number of spermatids in their testes. Consistent with this observation, we show that Slc12a2 is expressed in Sertoli cells, pachytene spermatocytes, and round spermatids isolated from wild-type animals. Our results indicate a critical role for NKCC1-mediated ion transport in spermatogenesis and suggest that the cytoplasmic domain of NKCC1 is essential in the normal functioning of this protein