Journey of the Egg: Necessity for Female Fertility

Since the origin of living organisms, the essential task of every organism is to pass the genetic code to a new living form. Mother nature has given the choice to spread genetic information to every organism for the survival of its own kind depending upon the complexity of the living creatures. For simple life forms such as bacteria, a cellular division serves as the easiest way to expand its gene pool. But for more complex organisms, including humans, reproduction was the only way to distribute the genetic information.

With the evolution of humans, the anatomy of the female body has undergone immense change narrowing the hipbone and thereby constricting the birth canal. This created a greater risk for the life of females during childbirth. In addition, the societal structure of the evolving early humans, where alpha male impregnates every female in his group, had put immense stress on the reproductive health of females. Hence for the greater survival of females, mother nature gave a unique strategy to the female body so that she can enjoy motherhood by giving birth and nurturing the baby during her prime reproductive age. In her old age, she utilizes her experience to support and care for other new mothers and enjoy her caring motherhood.

Humans, especially female-kind are gifted with an egg which is known as an oocyte. The egg is the largest cell in the body that holds the mother’s genetic information. Unlike males, females possess egg reserve with a definite number of eggs in the ovary. Throughout her reproductive age, the egg reserve depletes by the monthly cycle. This monthly cycle is known as the menstrual cycle. After reaching adulthood, monthly cyclicity allows her body to be well prepared for the pregnancy, then nurture her offspring if pregnancy occurs, and cease her reproductive life as menopause. Thus, females’ egg is prime important to sustain humankind.

The egg is wrapped around by the layer of cells within a small sac called a follicle within the ovary. The granulosa cells that surround the egg are in close connection with the egg via complex crosstalk through genes and proteins initiated by the superior moderator known as Luteinizing Hormone (LH). This ensures the timely release of a fertilizable egg from the follicle.

A monthly routine of the egg release from the ovary is not as simple as it sounds. During the process of egg release from the follicle, endothelin-2 (EDN2) acts as the survival gene which is essential to keep the egg and granulosa cells alive. EDN2 is awakened by the LH just prior to the egg release in the granulosa cells. The reason for EDN2 awakening is that at the time of egg release a peculiar condition arises where the granulosa cells and the egg are exposed to oxygen-deprived situation or hypoxic condition. But the initial awakening of END2 weak. Henceforth, hypoxia-inducible-factor-1-alpha (HIF1A) comes forward and acts as a rescuer of this hostile condition. HIF1A synchronizes and the positive energy of LH and negative energy of hypoxic condition to singular super energy and mediates the power to keep up EDN2 production in the granulosa cells. To remind you, my dear reader, granulosa cells are always in close connection with the egg.

Now, I would like to put the perspective of HIF1A as motorsport driver. As I mentioned earlier, HIF1A can power up END2 by facilitating the energy of LH, and hypoxic condition, however, the thrust is not enough. Hence, HIF1A encourages its co-driver called microRNA-210 (miR-210) to better use the negative energy of oxygen-deprived situation. This microRNA-210 acts as a navigator and directs HIF1A to stay on track. MiR-210 prevents the road-blocker i.e. glycerol-3-phosphate dehydrogenase 1-like gene where it dodges the harsh effect of road-blocker and supports HIF1A all the time. Altogether, HIF1A and miR-210 works as a single unit under the well-balanced energy of LH and hypoxic condition to boost EDN2 production. The elevated level of EDN2 in turn keeps the granulosa cells and the egg alive through the journey of egg release.

With the notion of the egg/oocyte is the key to the existence of humankind, I greatly appreciate those fellow humans who have adopted orphan kids and value every human life. Moreover, I would appreciate all the readers who trust the research that aims to solve the problems of infertility and have faith in science.

This article is based on the following research paper:

miR-210 and GPD1L regulate EDN2 in primary and immortalized human granulosa-lutein cells