A5025029867- Effects and risks of endocrine disrupting chemicals
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- Genetic factors in colorectal cancer
- Vitamin D Research Studies
- Renal and related cancers
- Genetic Associations and Epidemiology
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Estrogen and related hormone effects
- Digestive system and related health
- Colorectal Cancer Screening and Detection
- Phytoestrogen effects and research
- Urological Disorders and Treatments
- Hormonal and reproductive studies
- Birth, Development, and Health
- Reproductive Biology and Fertility
- Nutritional Studies and Diet
- Infant Nutrition and Health
- Glioma Diagnosis and Treatment
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- Biosensors and Analytical Detection
- Colorectal Cancer Treatments and Studies
- PI3K/AKT/mTOR signaling in cancer
- Ovarian function and disorders
University Hospital of Zurich
2025
University of Zurich
2025
Edinburgh Cancer Research
2003-2024
University of Edinburgh
2007-2024
Institute of Genetics and Cancer
2008-2024
Medical Research Council
1999-2022
Cancer Genetics (United States)
2019
Western General Hospital
1999-2018
MRC Centre for Reproductive Health
2001-2013
Queen's Medical Centre
2006-2013
Abstract This study investigated whether neonatal exposure of male rats to estrogenic compounds altered pubertal spermatogenesis (days 18 and 25) the changes observed resulted in long-term testis size, mating, or fertility 90–100). Rats were treated neonatally with a range doses (0.01–10 μg) diethylstilbestrol (DES; administered on alternate days from 2–12), high dose octylphenol (OP; 2 mg daily 2–12) bisphenol A (Bis-A; 0.5 vehicle, while maintained standard soy-containing diet. The effect...
This study aimed to identify the mechanism(s) for impairment of spermatogenesis in adulthood rats treated neonatally with estrogens. Rats were (days 2-12) 10, 1, or 0.1 microg diethylstilbestrol (DES), 10 ethinyl estradiol (EE), mg/kg a GnRH antagonist (GnRHa), vehicle and killed adulthood. DES/EE caused dose-dependent reductions testis weight, total germ cell volume per testis, Sertoli testis. number at 18 days age DES-treated was reduced dose dependently. GnRHa treatment changes these...
The role of androgens in the proliferation and maturation Sertoli cells (SC) development their capacity to support spermatogenesis remains poorly understood. We evaluated these functions complete androgen receptor knockout (ARKO) SC-selective (SCARKO) mice. Compared with controls, ARKO mice exhibited a progressive reduction SC number/testis, whereas SCARKOs showed minor changes, suggesting that effects on number are not mediated via direct action SCs. Immunoexpression anti-Mullerian hormone...
Fetal exposure of male rats to di (n-butyl) phthalate (DBP) induces testicular changes remarkably similar dysgenesis syndrome in humans; these include induction focal areas dysgenetic tubules otherwise normal testes. In searching for the fetal origins latter, we used image analysis show that 500 mg/kg DBP [embryonic day (E)13.5–20.5)] caused abnormal aggregation Leydig cells centrally testis. This was not due increase cell number, and size significantly reduced DBP-exposed animals, as were...
Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several these tagSNPs near bone morphogenetic protein (BMP) pathway loci. The penalty multiple testing implicit in GWAS increases attraction complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. strongest loci additional predisposition SNPs arguably those already known...
Certain phthalates can impair Leydig cell distribution and steroidogenesis in the fetal rat utero, but it is unknown whether similar effects might occur human.Our aim this study was to investigate of di(n-butyl) phthalate (DBP), or its metabolite monobutyl (MBP), on testosterone production aggregation (LCA) testis explants from human, compare results with vivo findings for DBP-exposed rats. We also wanted determine if DBP/MBP affects neonatal male marmoset.Fetal obtained [gestation day...
Introduction Hyperuricemia is a strong risk factor for gout. The incidence of gout and hyperuricemia has increased recently, which thought to be, in part, due changes diet lifestyle. Objective this study was investigate the association between plasma urate concentration and: a) food items: dairy, sugar-sweetened beverages (SSB) purine-rich vegetables; b) related nutrients: lactose, calcium fructose. Methods A total 2,076 healthy participants (44% female) from population-based case-control...
ABSTRACT: This study evaluated whether androgen action is altered in rats treated neonatally with diethylstilbestrol (DES) at a dose that induced reproductive tract abnormalities. Rats were on alternate days 2–12 10 μg DES and studied Day 18. DES‐induced abnormalities included 70% reduction testis weight, distension overgrowth of the rete, epithelial height efferent ducts, underdevelopment epididymal duct epithelium, vas deferens, convolution extra‐epididymal vas. In DES‐treated rats,...
BackgroundFetal exposure of male rats to di(n-butyl) phthalate (DBP) induces reproductive disorders similar those in human testicular dysgenesis syndrome (TDS), including infertility, cryptorchidism, focal “dysgenetic areas,” and Sertoli cell–only tubules the adult testis. Humans are widely exposed DBP, but at much lower levels than causing adverse effects rats.ObjectivesThe objective this study was evaluate end points affected by DBP action fetal life that relevant TDS, compare their dose...
Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal complicate interpretation such measurements. This is important to clarify if measurements are be applied humans. The present aim was evaluate effects prenatal manipulation production/action on growth AGD and rats. Pregnant rats were treated daily before...
<h3>Background and aims</h3> Shorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable may be an intermediate phenotype linked to genetic susceptibility CRC. <h3>Methods</h3> In a large sample, the study investigated whether candidate single nucleotide polymorphisms (SNP) in 'telomere biology' genes were telomere leucocytes. SNP CRC searched for separately. <h3>Results</h3> Carriers common allele at rs10936599,...
Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish rats when action/administration affects the if deficits MPW were rescuable postnatally. Thus, pregnant treated with flutamide during +/- postnatal testosterone propionate (TP) treatment. To assess growth...
Reproductive disorders that are common/increasing in prevalence human males may arise because of deficient androgen production/action during a fetal ‘masculinization programming window’. We identify potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) Leydig cell (LC) steroidogenesis partly explain this. In rats, LC size and intratesticular testosterone (ITT) increased ∼3-fold between e15.5-e21.5 which associated with progressive decrease the...
Whilst observational studies establish that lower plasma 25-hydroxyvitamin D (25-OHD) levels are associated with higher risk of colorectal cancer (CRC), establishing causality has proven challenging. Since vitamin is modifiable, these observations have substantial clinical and public health implications. Indeed, many agencies already recommend supplemental D. Here, we explore in a large Mendelian randomisation (MR) study using an improved genetic instrument for circulating 25-OHD.
Objective We assessed the effect of surgical resection colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. investigated relationship between circulating level CRC survival. Design sequentially sampled 92 patients undergoing resection, measured 25OHD CRP. For survival analyses, we assayed CRP in two temporally distinct patient cohorts (n=2006, n=2100) association outcome, systemic inflammatory response. Results Serial sampling revealed a...
This study has addressed concerns about possible effects of feeding human infants soy formula milk (SFM).This is a in marmosets, using mainly co-twin design. From 4-5 until 35-45 days age, males were fed by hand with either standard (cow) (SMA = controls) or SFM for approximately 8 h each day (2 at weekends) and intake related to bodyweight. Blood samples collected 18-20 age 13 sets co-twins plus two non-twin per group and, the later seven killed testes pituitary gland fixed cell...
Neonatal treatment of male rats with diethylstilboestrol (DES) or a gonadotrophin-releasing hormone antagonist (GnRHa) reduces final Sertoli cell number, an effect presumed to occur via suppression follicle-stimulating (FSH). As both treatments also suppress androgen action, we investigated whether androgens and oestrogens might affect nuclear volume/number in the rat using single combined that differentially affected FSH, testosterone oestrogen levels. flutamide (50 mg/ kg) significantly...
This marmoset study addresses concerns about feeding human male infants with soy formula milk (SFM).From age 4 to 5 days, seven co-twin sets were fed standard (SMA) or SFM for 5-6 weeks; blood samples subsequently collected at 10-week intervals. Testes from co-twins killed 120-138 weeks fixed cell counts.SFM- and SMA-fed twins showed normal weight gain; puberty started progressed normally, based on testosterone measurements. Body weight, organ weights (prostate, seminal vesicles, pituitary,...
Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesislike syndrome (TDS) male offspring. Earlier studies suggested altered Sertoli cell development/maturation may result, especially testes that become cryptorchid. This study quantitatively assessed numerical and functional development DBP-exposed compared (unilaterally) cryptorchid scrotal testes. Pregnant were gavaged with 500 mg/kg/day DBP or corn oil from embryonic (E) Days 13.5 21.5. Male offspring...
With the ongoing COVID-19 (Coronavirus Disease 2019) pandemic, caused by novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), there is a need for sensitive, specific, and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves detection viral RNA using RT-qPCR (quantitative reverse transcription PCR), with many commercial kits now available this purpose. However, these expensive, supply such in...
The primary purpose of this study was to establish whether Sertoli cells proliferate in the neonatal period marmoset monkey (Callithrix jacchus) and administration a long-acting GnRH antagonist (GnRHa) during phase induced any transient or permanent effects on cell number other aspect testicular development. Male co-twins (n = 9) were treated Weeks 1-14 with either vehicle GnRHa. Four sets examined at 18-22 (start infancy) 5 adulthood (92+ wk), determined using nucleator optical disector...
Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular changes similar dysgenesis syndrome in humans, including the formation focal 'dysgenetic areas' within post-natal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during abnormal large Leydig cell (LC) clusters foetal life and day (d) 4 groups intermingled attempt seminiferous tubules. It...