Genetic Blueprint of Female Reproduction Found

Carnegie In The News

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Chen-Ming Fan, ScienceAlert

Ovarian follicles may be the most important structures in biology. Female reproductive issues—birth defects, menopause, and in vitro fertilization—revolve around understanding ovarian follicles.

So do the basic sciences of developmental biology, evolution, and ecology. Ovaries contain thousands of follicles, each housing a single germ cell, the oocyte, in the process of developing into a mature egg to found the next generation. In addition to the oocyte, follicles contain hundreds of “granulosa cells,” which control how their oocyte develops by processes that are not well understood. Infertility results when follicles die or develop incorrectly. Embryonic development depends on the starting materials in the oocyte, and can lead to birth defects when the egg has flaws. A species’ ability to produce high-quality oocytes rapidly influences how it evolves and interacts with other species and the environment. 



This image shows a primordial follicle in an ovary. It consists of an immature egg called an oocyte (green) surrounded by a layer of supporting cells called granulosa cells (red).

Carnegie’s Wanbao Niu and Allan Spradling recently reported an important advance in understanding follicle development during its earliest and most critical phases. Mapping the genes that are expressed by the developing oocyte and its granulosa cells represent the key to understanding this fundamental process. The researchers used the mouse and the modern molecular biology approach called single-cell RNA sequencing. In single-cell RNA sequencing, messenger RNAs, the RNA containing the genetic sequence of a gene, are sequenced to reveal which genes are active in each ovarian cell. They sequenced 52,500 ovarian cells at seven different times during follicle development. The study covered follicle formation, meiosis (the special division sex cells use to generate new genetic combinations), and initial follicle storage that generates a reserve for use throughout life. 


The researchers read an average of 2,700 different genes per cell, which establishes a basic resource relevant to future studies of ovarian follicles and all the processes they influence. More than 2,500 genes changed during meiosis—more than previously known. Most important were gene changes mapped in granulosa cells, critically important cells that were shown to exist in two distinct subpopulations. The same basic process for making eggs appears to be used in species across the phylogenetic spectrum. Consequently, the basic genetic instructions for making mouse follicles reported in this study will help researchers understand egg production in diverse animals of all kinds.