Eggs & Embryos

Introduction

Human reproduction is highly inefficient by nature, with only ~30% of conceptions resulting in live births. The most common cause for reproductive failure and pregnancy loss is when the early embryo possesses the wrong number of chromosomes (aneuploidy). This is often incompatible with further development. Our project is trying to understand the molecular mechanisms that underly the high failure rate by asking one main question; how is the number of chromosomes controlled in the very first stages of human development?

A specialised cell division called meiosis produces eggs and sperm (gametes). Problems in meiosis cause a high proportion of human eggs to be faulty. Such eggs may have the wrong number of chromosomes, and this occurs more often in older women. This is known as the ‘biological clock’ of human female fertility.

Possession of the correct number of chromosomes is essential for normal human development. Therefore, fertilisation of such aneuploid eggs with a sperm can result in infertility, miscarriage, or genetic syndromes such as Trisomy 21 Down Syndrome. We aim to understand the biological processes that control the chromosome number in human eggs and early embryos, and determine if there are any changes in reproductively challenged patients. Our team of clinical reproductive scientists and cell biologists uses advanced microscopy to fluorescently label and examine structures inside human eggs and early embryos. We apply these methods to undertake research on meiosis in human immature eggs, and mitosis in the first division of the fertilised egg. We anticipate that our work will provide a better understanding of the pathways that control chromosome number in human eggs and inform future work to diagnose and treat infertility.

This is a collaborative project with research groups at the University of Edinburgh:

Adele Marston (Wellcome Centre for Cell Biology), Richard Anderson (Centre for Reproductive Health) & Evelyn Telfer (School of Biological Sciences).

Meet the Project Team

Professor Andrew McAinsh

Principal investigator

Email: A.D.MCainsh@Warwick.ac.uk

Professor Geraldine Hartshorne

Scientific director of the Centre for Reproductive Medicine (CRM UHCW)

Email: Geraldine.Hartshorne@Warwick.ac.uk

Aleksandra Byrska

PhD student

Dr Muriel Erent

Research Fellow

Dr Cerys Currie

Research Fellow

Dr Deborah Taylor

Higher specialist embryologist (CRM UHCW)

Jade Savage

Research nurse (CRM UHCW)

Soultana Kotsiopoulou

Research Midwife

Research Directions:

Meiosis and oocyte (egg) maturation (forming a healthy egg)

Oocytes (eggs) are formed through a specialised type of cell division known as meiosis. This process starts during fetal development with the assembly of bivalents – unique structures where two homologous chromosomes are held together. Importantly, meiosis is only completed decades later, when the same egg prepares for ovulation during the menstrual cycle. During this long period, the bivalent structure can deteriorate, and this effect becomes more prominent the older the egg is. This can result in chromosomal abnormalities (aneuploidy) in the egg, which can be associated with infertility, miscarriage or developmental syndromes such as Trisomy 21 Down Syndrome.

In our lab, we investigate the chromosome dynamics in meiosis, focusing on the effects of advanced female age on oocyte quality and meiotic progression. We use advanced techniques such as oocyte microinjection with fluorescent dyes to visualise chromosome movements in live oocytes.

Young egg spindle

Old egg spindle

Chromosomes in oocytes from a young (26 years old; left) and older (40 years old, right) woman. In eggs from younger women, all chromosomes align together, which helps them segregate correctly. In older eggs, some chromosomes drift away from the main line, which may cause issues during segregation.

The first mitotic division of the human embryo (forming a healthy embryo)

Once an egg is fertilised by a sperm, the resulting cell, known as a zygote, must divide into two cells. This division is important as it is the first time that the two parental genomes (from egg and sperm) merge. If chromosomes are incorrectly organised in the first division, the resulting cells can end up with surplus or missing chromosomes. This is known as mitotic aneuploidy, and can sometimes be associated with early embryo arrest, implantation failure and pregnancy loss. However, it is also known that embryos containing some aneuploid cells can result in genetically normal healthy live births, suggesting that aneuploidy can be tolerated or corrected by unknown processes in the human embryo.

In our lab, we investigate in detail the unique properties of the early divisions of human embryos. We recently discovered that chromosome segregation in the first division of the fertilised egg is highly error prone. Currently we are exploring the mechanisms and implications of these chromosome errors for further embryonic development.

immunofluorescent image of a 2-cell embryo

Recent Publications

Patel et al., 2015: Unique geometry of sister kinetochores in human oocytes during meiosis I. Biology Open, DOI: https://doi.org/10.1242/bio.016394

Currie et al., 2022: The first mitotic division of human embryos is highly error prone. Nature Communications, DOI: https://doi.org/10.1038/s41467-022-34294-6

Mihalas et al., 2023: Age-dependent loss of cohesion protection in human oocytes. Current Biology, DOI: https://doi.org/10.1016/j.cub.2023.11.061

Public Engagement

We engage in many outreach opportunities, including festivals such as Pint of Science or Science on the Hill. In June 2022, we created a collection of glass art pieces with guidance from a professional artist, David Mola. These have been displayed several times resulting in many people engaging and showing interest in our project. Working with the same artist, we also decorated some of laboratory glassware using sandblasting techinque.

Glass art display Doctoral Research Showcase

Glass art display at Warwick Doctoral Research Festival 2023

Sand-blasted glassware: beaker and conical flask decorated with oocytes and sperm

Glass art display at Science on the Hill 2024