A5023220284- Effects and risks of endocrine disrupting chemicals
- Toxic Organic Pollutants Impact
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- Carcinogens and Genotoxicity Assessment
- Prostate Cancer Treatment and Research
- Wound Healing and Treatments
- Sperm and Testicular Function
- Prostate Cancer Diagnosis and Treatment
- Reproductive Biology and Fertility
- PI3K/AKT/mTOR signaling in cancer
- Sexual Differentiation and Disorders
- Burn Injury Management and Outcomes
- Ovarian function and disorders
- Growth Hormone and Insulin-like Growth Factors
- Pressure Ulcer Prevention and Management
- Animal testing and alternatives
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Molecular Biology Techniques and Applications
- Birth, Development, and Health
- Surgical Sutures and Adhesives
- Heme Oxygenase-1 and Carbon Monoxide
- Environmental Toxicology and Ecotoxicology
- Immunotoxicology and immune responses
European Chemicals Agency
2023-2024
Finnish Safety and Chemicals Agency
2023-2024
The University of Sydney
2009-2022
Anzac Research Institute
2010-2022
Concord Repatriation General Hospital
2012-2022
Finnish Institute for Health and Welfare
2010-2014
The University of Melbourne
2013
Sydney Hospital
2008
Public Health Institute
2008
University of Eastern Finland
2004-2007
Significance A fundamental tenet of life-history theory is that reproduction and longevity trade off against one another. Experiments on invertebrates show that, rather than competing for limiting resources, lifespan are optimized different dietary macronutrient compositions. In mice, studies have yet to establish the relationship between balance, reproduction, lifespan. We evaluated effects macronutrients energy reproductive function. Indicators function (uterine mass, ovarian follicle...
Ovarian granulosa cells display strong androgen receptor (AR) expression, suggesting a functional role for direct AR-mediated actions within developing mammalian follicles. By crossing AR-floxed and anti-Müllerian hormone (AMH)-Cre recombinase mice, we generated cell-specific knockout mice (GCARKO). Cre assessed by lacZ activity, localized to 70%–100% of in most preantral antral follicles, allowing selected evaluation cell AR-dependent during follicle development. Relative wild-type (WT)...
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a notorious model compound of highly toxic environmental pollutants, polychlorinated dibenzo-p-dioxins (PCDDs). Their effects are mediated via cytosolic aryl hydrocarbon receptor (AHR). We studied the several dose levels TCDD on developing rat bone after maternal exposure at different times gestation and lactation in three differentially sensitive lines. Rat lines A, B, C differ their sensitivity to due mutated AHR (Ahrhw) line A another...
Prostate development and maturation requires stromal-epithelial interactions androgen action via the receptor (AR) within these compartments. However, specific roles of epithelial stromal AR in postnatal prostate differentiation are unclear. We used Cre-LoxP technology to determine phenotype mice with epithelial-selective genetic inactivation leaving functionally intact. find that abolished globally lacking a functional can be rescued by restricting knockout epithelium. show that, at 8 wk...
Research into gene expression enables scientists to decipher the complex regulatory networks that control fundamental biological processes. Quantitative real-time PCR (qPCR) is a powerful and ubiquitous method for interrogation of expression. Accurate quantification essential correct interpretation qPCR data. However, conventional relative absolute methodologies often give erroneous results or are laborious perform. To overcome these failings, we developed an accurate, simple use, universal...
Both testosterone and its nonaromatizable metabolite dihydrotestosterone (DHT) induce spermatogenesis in gonadotropin-deficient hpg mice. Surprisingly, because aromatization is not required, estradiol (E2) also induces increases circulating FSH mice, but the mechanism remains unclear. We studied E2-induced mice on an estrogen receptor (ER)-alpha (hpg/alphaERKO) or ERbeta (hpg/betaERKO) knockout wild-type ER (hpg/WT) background treated with subdermal E2 DHT implants for 6 wk. In hpg/WT...
Use of new approach methods (NAMs), including high-throughput, in vitro bioactivity data, setting a point-of-departure (POD) will accelerate the pace human health hazard assessments. Combining and exposure predictions into bioactivity: Exposure ratio (BER) for use risk-based prioritization utilizing NAM-based flags to indicate potential hazards interest further prediction or mechanism-based screening together comprise prospective management substances with limited traditional toxicity...
Male reproductive effects induced by in utero and lactational exposure to TCDD were analyzed three rat lines that are differently sensitive TCDD. Rats from A, B, C selectively bred TCDD-resistant Han/Wistar (Kuopio, H/W) TCDD-sensitive Long-Evans (Turku/AB, L-E) rats exhibited very different LD50 values for TCDD: >10,000, 830, 40 μg/kg males, respectively. The resistance line A was linked a mutated H/W-type aryl hydrocarbon receptor (Ahrhw) B unknown allele (Bhw). Line had no alleles....
Androgen action on sex accessory organs influences rodent fertility, but the mechanisms remain unclear and investigation is difficult without ability to restrict androgen in specific tissues. We used Cre-LoxP technology generate male mice with prostate epithelial-specific receptor deficiency (denoted PEARKO). In addition prostate, these males have reduced due tissue-selective inactivation seminal vesicle, epididymis, vas deferens, whereas testis unaffected. find that fertility of PEARKO was...
Postnatal inactivation of epithelial androgen receptor (AR) in prostate AR knockout (PEARKO) mice results hindered differentiation but enhanced proliferation cells. As this resembles the precancerous proliferative atrophy human prostates with undifferentiated intensively replicating cells, we utilized PEARKO to characterize response castration-induced involution a focus on identifying potential role stromal and responsiveness androgen-deprived epithelia aromatizable testosterone (T) or its...
The contribution of genetic factors to adult male reproductive system toxicity 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was analyzed in three rat lines differentially resistant TCDD acute lethality: line A, B, and C rats (selectively bred from TCDD-resistant Han/Wistar [Kuopio; H/W] TCDD-sensitive Long-Evans [Turku/AB; L-E] rats). resistance is linked a mutated H/W-type aryl hydrocarbon receptor allele A an unknown "B" B. Line do not have alleles. Mature B were given single oral doses up...
While estrogen action is the major driver of uterine development, androgens acting via androgen receptor (AR) may also promote growth as suggested by phenotypes in global AR knockout (ARKO) female mice. Because expressed endometrial glands, we generated (Cre/loxP) gland epithelium-specific ARKO (ugeARKO) to determine role gland-specific actions. However, epithelium not be required for normal development and function because ugeARKO females had fertility. To if exogenous can fully support...
// Soma Vignarajan 1 , Chanlu Xie 1,6 Mu Yao Yuting Sun 2 Ulla Simanainen 3 Paul Sved 4 Tao Liu 2,5 Qihan Dong Discipline of Endocrinology, Central Clinical School, Bosch Institute, Royal Prince Alfred Hospital, and Charles Perkins Centre, The University Sydney, NSW, Australia Children’s Cancer Institute for Medical Research, ANZAC Research institute, Sydney Camperdown, 5 School Women’s Health, UNSW Medicine, Australia, 6 Science Western Correspondence: Dong, email: Keywords :...
The androgen receptor (AR) is widely expressed in mammary cells of female mammals including humans and mice, indicating a possible role for AR-mediated actions breast development, function, pathology, although the specific mechanisms remain unclear. To elucidate action gland physiology we used AR-knockout (AR(Δex3)KO) mice with universally expressed, transcriptionally inactive AR protein harboring an in-frame deletion its second zinc finger. Although sexually mature wild-type (WT) AR(ex3Δ)KO...
A single maternal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day (GD) 13 can greatly impair ventral prostate, dorsolateral anterior and seminal vesicle development in wild-type C57BL/6 mice. The developmental stages at which these organs are most sensitive to TCDD exposure have now been investigated. Pregnant mice were dosed orally with 5 μg TCDD/kg or vehicle GD 13, their pups fostered birth dams the same treatment cross-fostered opposite treatment. Additional males had...