PhD Studentship: Developmental and physiological consequences of heat stress for pre-hatching and gastrulating cattle and pig embryos

Epidemiological evidence in humans indicates that acute heat exposure around the time of mating results in pregnancy loss, with potential long-term consequences on the offspring. Similar effects of acute heat stress on embryo survival and development have been noted in other species. Identifying underpinning mechanisms requires use of appropriate animal models. Farm animal and human embryos share many aspects of early embryonic development. Thus, in addition to being species of clinical importance in their own right, farm animals represent excellent models for the study of human embryogenesis.

This PhD will test the hypothesis that an acute period of heat stress around the time of mating epigenetically alters embryo development in a manner that can compromise pregnancy establishment, and the health and wellbeing of offspring from surviving embryos.

The studentship will undertake detailed morphokinetic, histological, metabolic and molecular analyses of bovine and porcine embryos up to and including gastrulation. In so doing, the project will complement in vivo assessments of porcine embryo development (extending to F2 embryos) and measurements of cardiometabolic health in offspring (F1). Specifically, this PhD will address the following three objectives:

(1) Establish morphokinetic, metabolic and epigenetic effects of acute heat stress in cattle and pig pre-hatching (elongation) embryos.

(2) Establish consequences of such effects on cell fate in gastruloids formed from stem cells derived from control or heat-stressed pig blastocysts.

(3) Establish cardiometabolic health in adult male and female porcine offspring 

A range of temperatures (representing extremes of core-body temperature) will be assessed during in vitro embryo culture. State-of-the-art morphokinetic techniques will include using time-lapse microscopy, complemented by immunohistological quantification of cell-lineage fate. Metabolic responses will be established by extra-cellular flux analyses of mitochondrial function. The study will then characterize (lineage markers, karyotype) and sex stem-cell lines from Control and Hyperthermic treated embryos using established in-house protocols. Epigenetic status will be determined which will provide some insight into potential long-term developmental consequences of short-term heat stress during the study period.

Further information and Application:

Applicants should have a minimum of a 2.1 undergraduate degree or a minimum of a 2.2 degree and a Master’s degree in Agriculture, Animal Science, Veterinary Science, Nutrition or similar subjects.

Informal enquiries may be addressed to the principal supervisors: david.gardner@nottingham.ac.uk and/or kevin.sinclair@nottingham.ac.uk

Candidates should apply online and include a CV. When completing the online application form, please select the School of Veterinary Medicine and Science, then PhD Veterinary Medicine and Science (36m) and, once submitted, send your student ID number to SV-PG-VET@exmail.nottingham.ac.uk. Any queries regarding the application process should be addressed to SV-PG-VET@exmail.nottingham.ac.uk.

Interview Date: TBC

Start Date: 1^st April 2025

Closing date: 24^th February 2025

Eligibility for Funding: This is a fully funded studentship open to UK nationals only. Fee status will be assessed upon application.