Tailor made interactions between the uterus and embryo

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Calf feeding. © INRA, BOSSENNEC Jean-Marie

Calf feeding. © INRA, BOSSENNEC Jean-Marie

One of the crucial stages of gestation is implantation of the embryo in the uterus, in contact with a tissue called the endometrium. However, the mechanisms that enable this implantation remain largely unclear. A Franco-American collaboration co-led by INRA research scientists has revealed that intense and fine-tuned crosstalk is established between the embryo and endometrium, allowing them to adapt to each other. Working in cattle, the scientists analysed the expression of genes in the embryo and endometrium at the start of gestation. They showed that many of the biological processes at work in the two tissues are closely correlated. Published in Plos Biology , these findings may help to better understand how defects in reciprocal adaptation processes between the endometrium and embryo may lead to early pregnancy failures in mammals.

In cattle, 18 to 20 days after fertilisation, a decisive event for gestation occurs when the embryo enters into contact with the endometrium, the mucous cell layer that covers the internal surface of the uterus. This is the initiation of implantation, the key process that allows the embryo to attach itself to the uterus and which leads to placental and foetal development. It was already known that this implantation depended on endometrium-embryo interactions; indeed, the same team had demonstrated that the endometrium is a dynamic tissue that reacts differently whether the embryo was produced by artificial insemination, by in vitro fertilisation or by cloning 1 . In their new study, the scientists focused in more detail on the communication that is established between the embryo and endometrium at the time of implantation in cattle ( Bos taurus ).

To achieve this, they studied heifers at the 18th day of gestation and analysed all the messenger RNA produced by the embryonic tissue that would form the future placenta and its paired endometrium. This transcriptomic analysis was able to identify all the genes expressed at a precise moment, thus revealing the biological processes ongoing in the cells. The team observed numerous close correlations of expression between the two tissues: the level of expression of 430 genes in the endometrium correlated with that of 451 genes in the embryo. The scientists thus revealed the extreme complexity of the implantation process and its finely tuned and precise regulation, which notably varied from one female to another and was specific to each pregnancy.

This is the first study to have simultaneously analysed gene expression in an embryo and its paired uterus. In cattle, the high level of failed pregnancies, reaching around 40-50% after the use of reproductive biotechnologies (transfer of in vitro embryos) could be explained by defective interactions between the uterus and embryo. A more limited adaptive capacity of the endometrium in certain recipients may thus explain why embryos classified as appropriate for transfer do not achieve implantation. Phenomena such as early pregnancy failures in both cattle and women may therefore originate from defects in the crosstalk between the endometrium and embryo. This work constitutes a major advance in our detailed understanding of the early stages of pregnancy and offers research opportunities to improve full-term pregnancy rates following embryo transfer.

1 presse.inra.fr/en/Pr­ess-releases/Low-birth-rate-after-cloning

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