Unravelling the effect of divergent concentrations of progesterone in early pregnancy on foetal development in the cow

Project Information

HEALTHYFOETUS

Grant agreement ID: 101021311

DOI

10.3030/101021311

Project closed

EC signature date 24 March 2021

Start date 1 September 2021

End date 31 August 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 196 590,72

EU contribution

€ 196 590,72

Coordinated by

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Ireland

Periodic Reporting for period 1 - HEALTHYFOETUS (Unravelling the effect of divergent concentrations of progesterone in early pregnancy on foetal development in the cow)

Reporting period: 2021-09-01 to 2023-08-31

Summary of the context and overall objectives of the project

In ruminants, combined efforts of researchers and producers have led to genetic advances, increasing beef and milk yield. However, improving reproductive efficiency is still an area to fulfil. While livestock production is critical to ensure food security and sustainable development at a global level, the environmental impact is a consequence of concern. Higher herd fertility decreases the production of greenhouse emissions per unit of food production. Therefore, improving reproductive efficiency through a deeper understanding of the underlying physiological and molecular regulation of pregnancy leading to the development of healthy offspring will significantly contribute to social and economic sustainability in agriculture and food production, in line with the UN Sustainable Development Goals. Pregnancy in mammals is a highly complex process driven in early pregnancy mainly by the concentrations of the progesterone hormone ([P4]), which regulate the dialogue between the embryo/foetus and the maternal environment. Previous studies have shown that in cattle, divergent [P4] early in pregnancy is related to differences in conceptus length and survival. However, the consequences of suboptimal [P4] for later foetal development were largely unknown. The overall objective of the HEALTHYFOETUS project was to determine the effect of high [P4] early in early pregnancy in the development of the maternal-foetal-placental unit in the cow. Our results demonstrated that embryos exposed to a uterus primed with higher [P4] underwent enhanced development reflected in higher weight and size at the beginning of the foetal period (42 days of gestation). Furthermore, we investigated those foetuses to test the hypothesis that the observed variations in foetal growth also impacted the molecular profile of organs differentiated by that early period, such as the liver, gonads, and heart. Finally, we identified biomarkers in the maternal blood to accurately predict foetal weight at this gestational stage. In conclusion, the execution of this project shed light on the biological underpinnings of maternal–fetal development in ruminants and allowed us to better comprehend the complex action of P4 in the uterus during the first days of the oestrous cycle and how it can still affect the developing foetus at 42 days of gestation.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

This project consisted of a main experiment where 107 heifers were randomly assigned to one of the two following groups: those receiving a Day 7 embryo on Day 7 of the cycle (n = 49, control group) and those transferred a Day 7 embryo on Day 9 of the cycle (n = 58; high progesterone group). Progesterone concentrations were determined each day from Day 3 after oestrus to the day of embryo transfer. Pregnant heifers were slaughtered at Day 42 of gestation for foetal and placental morphometric measurements. Additionally, samples from the foetal liver, heart and gonads, and the maternal whole blood samples were collected for mRNA-sequencing, while the maternal plasma and amniotic fluid samples from each foetus were subjected to microRNA-sequencing. Results demonstrated that embryos exposed to a uterus primed with higher progesterone underwent enhanced development reflected in higher weight and size at the beginning of the foetal period, foetal growth impacted the maturation of the internal organs (reflected by their molecular profile), and the maternal blood transcriptome can be harnessed to predict foetal weight. The fellow actively participated in the work involving the animals and sample collection and processing. She was responsible for the data analysis, results interpretation and scientific writing of abstracts and articles. The results were disseminated through multiple conference abstracts presented at international conferences, one of which was selected for an oral presentation (19th International Congress on Animal Reproduction. Bologna, Italy. June 2022, Mammalian Reproduction Gordon Research Conference. Mount Snow. Vermont. USA. August 2022 and 49th Annual Conference of the International Embryo Transfer Society. Lima, Peru. January 2023) and two articles published in high-impact journals (Theriogenology 2023, 200:25-32 and Biology of Reproduction 2023. DOI: 10.1093/biolre/ioad103). Two more articles are in preparation.
Additionally, the fellow collaborated on several other projects undergoing in the host lab. Her participation led to the additional publication of three abstracts as first author and five as a co-author, all of them presented at international conferences (19th International Congress on Animal Reproduction. Bologna, Italy. June 2022, 49th Annual Conference of the International Embryo Transfer Society. Lima, Peru. January 2023, and 11th International Ruminant Reproduction Symposium. Galway, Ireland. May 2023), and two articles as first author (PLoS One 2023, 18: e0290689 and Journal of Dairy Science 2023, 105:10033-10046) and three as co-author (Frontiers in Cell and Developmental Biology 2022, 10:950443, Theriogenology 2023, 211:1-10, Journal of Dairy Science 2023, In press). The fellow was one of the invited keynote speakers at the 11th International Ruminant Reproduction Symposium held in Galway, Ireland. Her presentation contained data emanating from this project, aiding in their dissemination and further outreach of the Marie-Curie Actions.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Results from this project have deepened the scientific knowledge about the relationship between the maternal environment and the conceptus in cattle, a species with a central role in food production. A better comprehension of the mechanisms involved in this critical and tightly regulated uterine-conceptus crosstalk can lead to intervention actions and / or the development of new tools aimed to improve pregnancy rate after the application of assisted reproductive technologies, such as embryo transfer. Therefore, results from this project significantly contribute to the attainment of social and economic sustainability in agriculture and food production, a crucial objective in the face of an ever-increasing global population.

Methodology and main results of the HEALTHYFOETUS project