A Gift from the Womb

Studies suggest that the uterus may contribute genetic material, in the form of microRNAs, which may contribute to overall embryo health.

It has been assumed that the uterine or maternal environment provides nutritional support to the growing and developing embryo and fetus, but not genetic information. Now some scientific information is breaking this original dogma, and suggesting that the uterus may also contribute genetic material which can determine the overall health of the embryo.

Researchers at the Fundacion Instituto Valenciano de Infertilidad (FIVI) have found that women secrete small packages of genetic information in their endometrial fluid called microRNAs, and 6 micro-RNAs have been identified to be present during the "window of implantation" (WOI). These micro-RNAs are small pieces of genetic information that control how other genes are being expressed. These micro-RNAS are protected in little protein coated vesicles called “exosomes” to prevent break-down. This study has shown that within the uterus, the early pre-implantation embryo is bathed in fluid that contains micro RNA. Once absorbed and incorporated into the embryo, the maternal micro-RNAs can then modify how genes in the embryo are made into proteins, thus contributing to the fate and health of the embryo. Micro-RNAs are instrumental in the turning on and off of genes, known as epigenetics.

Of the 6 micro-RNAs identified during the WOI, Hsa-miR-30d is thought to be the most important because it is the most highly produced during the WOI. Hsa-miR-30d is transported and incorporated into the pre-implantation embryo by protective exosomes.

The FIVI group tested the potential function of Hsa-miR-30d by observing the role of micro-RNA in a mouse model. They found that the cells surrounding the exterior of the mouse embryos (trophectoderm) have pores (or holes) through which exosomes are absorbed and incorporated. The absorption of micro-RNA correlated with the higher production of molecules that allow the embryo to “stick” to the uterus. When the researchers took isolated Hsa-miR-30d and added it directly to mouse embryos, the mouse embryos had a higher rate of pregnancy.

These studies strongly suggest that the maternal uterine environment has an important role in the genetic modification of pre-implantation embryos, and can potentially impact numerous important outcomes. This could be short-term outcomes such as implantation efficiency of the embryo, or longer-term outcomes such as risk of adult diseases thought to be related to the intrauterine environment during embryonic and fetal life. Such diseases include diabetes Type 2, obesity, metabolic syndrome and others.

In conclusion, human maternal micro-RNAs are secreted by the endometrium and may be important in the regulation of embryonic genes (in a mouse model). This suggests that maternal genetic material can potentially modify embryonic genetics and thereby modify and contribute to embryonic health. This study introduces the novel concept of genetic modification of embryos by the maternal uterine environment, which challenges not only our concept of pregnancy using one's own eggs, but also embryo modification in the context of donor eggs or gestational surrogacy.

We look forward to more studies elucidating these interesting bidirectional interactions between the maternal uterus and pre-implantation embryo.

Source

1. Vilella F et al. Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome. Development. 2015 Sep 15;142(18):3210-3221.