In this blog post, we will look at the biochemical reasons why early embryos choose lactic acid as their main energy source instead of glucose, and the significance of metabolic changes according to the stage of development.
Metabolism refers to all biochemical processes involved in the formation and maintenance of living organisms and the supply of ATP, the energy required for these processes. These metabolic processes are highly regulated at the cellular level and are essential for biological survival and growth.
One of the main biochemical reactions of metabolism for obtaining energy within cells is centered on pyruvate. Pyruvate is generally produced through glucose breakdown metabolism or lactic acid metabolism, especially through the activity of LDH (lactate dehydrogenase). The pathway that uses glucose requires more enzymes and reaction steps than the pathway that uses lactic acid, so it is relatively less energy-efficient and its metabolic regulation is also complex. Nevertheless, since most living organisms can obtain glucose relatively easily from the environment, under normal conditions, they mainly produce ATP through glucose-based metabolic pathways. On the other hand, lactic acid-based metabolic pathways are activated only under specific conditions, such as when temporarily accumulated lactic acid in the body is converted into an energy source after intense exercise.
Energy metabolism is not limited to the production of ATP, but is organically linked to the structure and function of cells and their various roles within tissues. Of course, not all cells perform metabolism in the same way, but the core structure of metabolic pathways does not change significantly from cell differentiation to cell death. However, as an exception, early embryonic cells of developing mammals exhibit metabolic patterns that are very different from those of somatic cells. Their main metabolic pathways change depending on the stage of development, and their energy supply systems also change accordingly.
In particular, fertilized eggs and early embryos begin their metabolic activities by relying on enzymes already accumulated during egg formation and transcripts for protein synthesis. Cells at this stage do not have a sufficient set of enzymes to convert glucose to pyruvate, but instead contain high levels of LDH.
As a result, early embryos use lactic acid metabolism through LDH activity as their main energy source rather than the glucose breakdown pathway. In other words, embryos at this stage obtain most of the ATP they need through the conversion of lactic acid to pyruvic acid. This activity of LDH creates a strong reducing environment within the cytoplasm, enabling rapid cell division and complex biosynthetic pathways that are rarely seen in somatic cells.
This plays a crucial role in supplying sufficient ATP for the rapid cell division that occurs during the cleavage stage. However, in the latter half of the cleavage stage, when the embryo passes the morula stage and develops into a blastocyst and implants in the uterus, the metabolic system of the cells gradually changes to that of somatic cells. From this point on, ATP production through glucose metabolism becomes the main energy pathway. This means that the embryo no longer relies on enzymes accumulated in the egg, but survives by forming enzyme groups through its own gene expression.
In most mammals, including humans, early embryos cannot obtain nutrients through the placenta until it is formed. Therefore, eggs do not accumulate large amounts of nutrients in advance, and embryos obtain the necessary nutrients through the endometrial fluid secreted inside the reproductive tract during this period. Eggs ovulated from the ovaries meet sperm in the ampulla of the fallopian tube and become fertilized eggs, which then pass through the isthmus of the fallopian tube and rapidly differentiate into the two-cell stage, four-cell stage, and eight-cell stage. By the time they reach the uterus, they develop into blastocysts and implant themselves in the endometrium in the form of a blastocyst.
Interestingly, the physiological environment of the reproductive tract also changes gradually according to the stage of embryo development. The composition of the endometrial fluid is adjusted according to the stage, and the metabolic processes of the early embryo, which needs to secure external energy sources, also adapt to these environmental changes. Therefore, the balance between ATP synthesis and biosynthesis is strictly regulated, and a stable supply of pyruvate is essential, especially during the rapid division of cells. For this reason, the concentration of lactic acid is relatively high in the isthmus of the fallopian tube, which helps the early embryo to obtain pyruvate smoothly and synthesize ATP based on it. In fact, the reproductive organs of mice have excellent environmental control capabilities, which support the stable metabolism of early embryos.
On the other hand, the developmental stage at which the metabolic mode of embryonic cells changes varies slightly depending on the animal species. For example, in mice, the transcripts accumulated in the egg are already depleted in the two-cell stage, and self-gene expression begins. In contrast, this change occurs between the four-cell stage and the eight-cell stage in pig embryos. This means that glucose metabolism begins later in pig embryos than in mice, and that it takes longer for embryos to develop independent metabolic control.
Although early embryos require a wide range of nutrients, simple culture media containing glucose, pyruvate, and lactate are commonly used in laboratory settings. At this point, if the concentration of each substance is adjusted according to the stage of development, the fertilized egg can develop steadily to the blastocyst stage. These culture conditions can be used as basic data for understanding metabolic adaptation in environments outside the laboratory and for precisely controlling the early development of living organisms.
As such, the metabolism of living organisms, especially the energy metabolism of early mammalian embryos, has a significance that goes beyond simple ATP production. It is a complex and sophisticated regulatory mechanism closely related to the timing of gene expression, the reproductive tract environment, and cell differentiation. By understanding this, we can explain the mysteries of early life in more detail and lay a scientific foundation for applications in various fields, such as reproductive medicine, biotechnology, and stem cell research. The beginning of life is quietly but miraculously taking place in these minute metabolic reactions.
