Research title: Assessing the effects of low-level exposure to chemical mixtures on DNA methylation, oxidative stress and temporal health
My research focuses on the impact of co-exposure to a wide variety of chemicals, at very low doses, through the environment.
Over the past 100 years there has been an enormous increase in the development and production of chemicals. Currently there are over 84,000 chemicals in commerce, with roughly 8,700 chemicals commonly used across various industries. Many chemicals find their way into the environment, leading to human exposure through the air, food, and water.
Routine monitoring of chemicals in the environment and human samples shows levels generally stay below levels determined to be safe. However, the determination of safe levels is derived from the testing of chemicals individually. There is increasing evidence that co-exposure to chemicals in mixtures may lead to adverse effects at lower levels than when exposed to chemicals individually. Consequently, it has been suggested that exposure to low levels of chemical mixtures could be a contributing factor in a number of increasingly prevalent conditions: reductions sperm quality and male fertility, increases in diseases of the immune system, increases in metabolic diseases, etc.
My research is concerned with the effects of exposure to many chemicals, at low levels, during pregnancy, on the testicular development of offspring. To do this we use a unique model which utilises biosolids, a wastewater treatment by-product, that reflects human exposure in terms of complexity and concentration. When sheep are grazed on biosolids treated pasture (as is a common agricultural practice), environmental chemicals can be measured in maternal tissues as well as tissues of their offspring. By comparing sheep which grazed on biosolids treated pasture with those which grazed on pasture fertilised with inorganic fertiliser, I have documented exposure-induced adverse effects in the testes of offspring. Using nanopore sequencing I have investigated changes in transcriptome and suggested putative mechanisms which may underlie this phenotype, and potentially testicular dysgenesis syndrome in humans, an increasingly prevalent reproductive disease.
Elcombe, C.S., Monteiro, A., Ghasemzadeh-Hasankolaei, M., Evans, N.P., Bellingham, M., 2021. Morphological and transcriptomic alterations in neonatal lamb testes following developmental exposure to low-level environmental chemical mixture. Environ. Toxicol. Pharmacol. 86, 103670. https://doi.org/10.1016/j.etap.2021.103670
Elcombe, C.S., Evans, N.P., Bellingham, M., 2022. Critical review and analysis of literature on low dose exposure to chemical mixtures in mammalian in vivo systems. Crit. Rev. Toxicol. (In production).
Elcombe, C.S., Monteiro, A., Elcombe, M.R., Ghasemzadeh-Hasankolaei, M., Sinclair, K.D., Lea, R., Padmanabhan, V., Evans, N.P., Bellingham, M., 2022. Developmental exposure to real-life environmental chemical mixture programs a Testicular Dysgenesis Syndrome-like phenotype in prepubertal lambs. Environ. Toxicol. Pharmacol. (In production).
I am a demonstrator for the School of Life Sciences and the School of Veterinary Medicine.
Following my undergraduate studies and gaining a BSc in biotechnology I conducted toxicological research through employment in a contract research organisation. After 6 years working in industry I returned to higher education, firstly gaining an MSc in drug discovery and development, and now pursuing a doctoral degree.
I am a member of the British Toxicology Society and the Royal Society of Biology.