The Effects of Endocrine Disrupters on Fetal Male Rat Testicular and Adrenal Development

Many of the reproductive disorders that emerge in adulthood have their origin during fetal development. Numerous studies have demonstrated that exposure to endocrine disrupting chemicals can permanently affect the reproductive health of experimental animals. In mammals, male sexual differentiation and development are androgen-dependent processes. In rat, the critical programming window for masculinization occurs between embryonic days (EDs) 15.5 and 19.5. Disorders in sex steroid balance during fetal life can disturb the development of the male reproductive tract. In addition to the fetal testis, the adrenal cortex starts to produce steroid hormones before birth. Glucocorticoids produced by the adrenal cortex are essential for preparing the fetus for birth. In the present study, the effects of exposure to endocrine disrupters on fetal male rat testicular and adrenal development were investigated. To differentiate the systemic and direct testicular effects of endocrine disrupters, both in vivo and in vitro experiments were performed. The present study also clarified the role of desert hedgehog signalling (Dhh) in the development of the testis. The results indicate that endocrine disrupters, diethylstilbestrol (DES) and flutamide, are able to induce rapid steroidogenic changes in fetal rat testis under in vitro conditions. Although in utero exposure to these chemicals did not show overt effects in fetal testis, they can induce permanent changes in the developing testis and accessory sex organs later in life. We also reported that exposure to antiandrogens can interfere with testicular Dhh signalling and result in impaired differentiation of the fetal Leydig cells and subsequently lead to abnormal testicular development and sexual differentiation. In utero exposure to tetrachlorodibenzo-p-dioxin (TCDD) caused direct testicular and pituitary effects on the fetal male rat but with different dose responses. In a study in which the effects of developmental exposure to environmental antiandrogens, di-isononylphthalate and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p’-DDE), on fetal male rat steroidogenesis were investigated, chemicals did not down-regulate testicular or adrenal steroid hormone synthesis or production in 19.5-day-old fetal rats. However, p,p’-DDE-treatment caused clear histological and ultrastructural changes in the prenatal testis and adrenal gland. These structural alterations can disturb the development and function of fetal testis and adrenal gland that may become evident later in life. Exposure to endocrine disrupters during fetal life can cause morphological abnormalities and alter steroid hormone production by fetal rat Leydig cells and adrenocortical cells. These changes may contribute to the maldevelopment of the testis and the adrenal gland. The present study highlights the importance of the fetal period as a sensitive window for endocrine disruption.Siirretty Doriast

The effects of perfluorooctanoic acid (PFOA) on fetal and adult rat testis

Perfluorooctanoic acid (PFOA) is a widely dispersed synthetic chemical, which accumulates in living organisms and has been connected with male reproductive disorders. To monitor the effects of PFOA, fetal rat testes or seminiferous tubule segments (stage VII-VIII) of adult rats were cultured in 0–100 μg/ml PFOA for 24 h. Afterwards, cAMP, progesterone, testosterone and StAR protein levels were measured from the fetal testes culture. Measurements were combined with immunohistochemistry, immunofluorescence, TUNEL and flow cytometric analysis to monitor cell death in somatic and germ cells. This study shows that the levels of cAMP, progesterone, testosterone and expression of StAR decreased significantly in PFOA 50 and 100 μg/ml. PFOA affected cell populations significantly by decreasing the amount of diploid, proliferating, meiotic I and G2/M-phase cells in adult rat testis. However, PFOA did not affect fetal, proliferating or adult rat Sertoli cells but an increased tendency of apoptosis in fetal Leydig cells was observed.</p

Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180): A postnatal follow-up study in rats

PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions

Toxicological Profile of Ultrapure 2,2 ',3,4,4 ',5,5 '-Heptachlorbiphenyl (PCB 180) in Adult Rats

Peer reviewe

A Montessori inspired pedagogy challenges high achieving students in mathematics : A qualitative study regarding strategies preferred to challenge and stimulate high achieving students in mathematics by teachers who use a Montessori inspired pedagogy among student ́s between 7 and 9 years old.

Studiens syfte var att ta reda på vilka strategier lärare som använder en Montessori-inspirerad pedagogik anser stimulerar och utmanar högpresterande elever i matematik samt om de upplevde några svårigheter eller problem med att undervisa högpresterande elever i matematik. För att undersöka det har sex kvalitativa intervjuer genomförts med lärare som har varit eller som är verksamma i årskurserna 1-3. Resultatet av intervjuerna visar att lärarna har en gemensam uppfattning om att en Montessori-inspirerad pedagogik utmanar och stimulerar högpresterande elever i matematik eftersom grundtanken i Montessori-pedagogiken är "eleven i centrum". Det här innebär att lärarna måste utgå från varje elevs förutsättningar, behov och aktuella kunskapsnivå. I resultatet framkommer också att lärarna använder sig av olika strategier i form av matematikbok från en högre årskurs, special- och fördjupningsområden, åldersintegrering och lärande med flera sinnen för att stimulera och utmana de högpresterande eleverna matematiskt. Det framgår också i resultatet att lärarna inte upplever några större problem eller svårigheter i undervisningen av högpresterande elever i matematik. De belyser ändå att den egna matematiska kompetensen, tidsbrist och eget kontrollbehov ibland kan utgöra hinder för att stimulera och utmana de högpresterande eleverna tillräckligt. Utifrån studien kan man dra slutsatserna att lärare som använder en Montessori-inspirerad pedagogik lägger stor vikt vid att hitta rätt strategi för rätt elev, vilket bidrar till att de högpresterande eleverna får utmaning och stimulans. De olika hindren som lärarna belyser skulle kunna minskas med fortbildning och samarbete mellan årskurserna.

Ordning och reda i genusordningen? : En analys av fyra skönlitterära böcker

I denna uppsats har de fyra skönlitterära titlarna Kort kjol, Hey Dolly, Den osynlige och Låt den rätte komma in analyserats. Dessa används i svenskundervisning på grundskolans senare år och på gymnasiet. Som teoretisk referenspunkt har genus- och queerteoretiska perspektiv använts. Detta för att få syn på hur den heteronormativa genusordningen framställs och eventuellt problematiseras. Heteronormativiteten ses således som avgörande för karaktärernas skapande av genus. Avstamp tas i kursplanerna då skönlitteraturen, enligt dessa, är av avgörande betydelse för elevernas skapande av identitet. Uppsatsen har en litteratursociologisk ansats för att belysa relationen mellan skönlitteratur och samhälle. Metoden är kvalitativ textanalys och boksamtal. Resultatet av analyserna visar att den heteronormativa genusordningen till stor del reproduceras i de fyra titlarna även om den i två av dessa titlar är mycket mindre påtaglig. Det finns i samtliga titlar karaktärer som mer eller mindre utmanar den heteronormativa genusordningen. Det är dock i de två titlarna, Låt den rätte komma in och Hey Dolly, som vi får möta de stora normbrytarna. Dessa karaktärer utmanar och problematiserar den heteronormativa genusordningen både genom hur de framställs och genom deras förhållande till andra. Uppsatsen synliggör således vilka "förebilder" och vilken samhällsnormer som råder i de analyserade böckerna. Alltså de "förebilder" och samhällsnormer som eleverna som läser dessa böcker får möta.The aim of this paper is to analyse how normative heterosexuality works in the creation of gender in four fiction titles used in the school subject Swedish. A gender and a queer perspective are used when analyzing the characters in the texts. According to queer theory, heteronormativity plays a decisive role in the creation of gender. The syllabus of the subject Swedish serve as the starting point as they proclaim that literature has a decisive influence on pupil's creation of identity. The results of the analyses showed that the heteronormative gender structure exists and works in the books. But the result also shows that there are several characters that challenge the structure by breaking social norms and thereby creates possible gender positions

Symptoms that may be stress-related and lead to exhaustion disorder: a retrospective medical chart review in Swedish primary care

Abstract Background Mental illness, and particularly stress-related disorders such as exhaustion disorder, is continuously increasing in today’s society. It is important to identify patients who consult for potentially stress-related symptoms early, before the stress condition develops into an exhaustion disorder. The purpose of the study was to investigate the frequency of different presenting complaints for which patients had consulted in the two years preceding receipt of their exhaustion disorder diagnosis, and to explore potential associations between stress-related presenting complaints and demographic factors, as well as comorbidity and other potentially stress-inducing factors. Methods This was a retrospective medical chart review of presenting complaints of adult patients with exhaustion disorder two years preceding receipt of diagnosis at a primary healthcare centre in western Sweden. Results Exhaustion disorder was diagnosed in 126 patients at the healthcare centre during the study period. Charts were available for 115 patients (76% women, mean age 47 years). Charts were reviewed with regard to presenting complaints, demographic data and comorbidity. Average number of general practitioner visits during the two years preceding the diagnosis was 5.2 (SD 3.7). The two most common complaints were infection and anxiety/depression, presented by 49% and 46%, respectively. Other stress-related complaints seen to in more than 30% of the patients were stress, other pain, fatigue, gastrointestinal symptoms, and sleep disturbances. Back pain and fatigue were more frequent in patients over 40 years. A majority of the patients also had mental (53%) or somatic (61%) comorbidity. Comorbidity was more frequent in older patients. No significant gender differences were found. Conclusions Patients with exhaustion disorder appear to consult their general practitioner numerous times with stress-related complaints in the years preceding their diagnosis. The findings indicate which presenting complaints general practitioners may need to be more attentive to so that patients at risk of developing exhaustion disorder can be identified earlier and get the support they need. Addressing stress factors earlier in the course of illness and preventing the development of exhaustion disorder may contribute to a reduced burden for both individual patients and for society, with a reduction in sick leave and societal costs for mental illness

Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB 180):a postnatal follow-up study in rats

Abstract PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7−10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions