Follicular Fluid redox involvement for ovarian follicle growth

Abstract

As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene such process is unknown but it is a critical issue in reproduction.In fact, important proteins in the FF, that regulate follicle growth and oocyte quality, exhibit cysteine residues at specific points, whose untoward oxidation would result in functional loss. Therefore, preservation of controlled oxidative conditions in the FF is a requirement for the fine-tuned oocyte maturation process. In contrast, its disturbance enhances the susceptibility to the establishment of reproductive disorders that would require the intervention of reproductive medicine technology.

Keywords: Cumulus Oophorus cells; Follicular fluid; Oocyte maturation; Oxidative stress.

Fig. 1

Essential structure of the follicle and simplified overview of cumulus oophorus cell and oocyte interaction. a Advanced pre-antral stage follicle, showing the two compartments: the antrum containing the follicular fluid (FF) and the cumulus oophorus (c.o.) cells around the oocyte. b The magnification shows the relation of zona pellucida (z.p.) to the oocyte and the c.o. cells. C. granulosa cell natriuretic peptide type C (NAPC) interaction with the c.o. cells NPR2 receptor that is promoted by oocyte secretory factors (OSFs) results in cGMP enhanced synthesis and its transport to oocytes along the extensions of c. o. cells that protrude through the zona pellucida (ZP). In the oocyte, it blocks phosphodiesterase-3A, which maintains cAMP high and the oocyte in prophase I arrest. Rabbit ovary. Bar in A and B: 100 μm

Fig. 2

Endogenous production of superoxide. Electrons generated in mitochondria, endoplasmic reticulum and cell membrane electron transport chains, and oxidation catalyzed by a diversity of enzymes, partially reduce oxygen into superoxide anion (O₂ ^•–,); this is dismutated by superoxide dismutase (SOD) into O₂ and H₂O₂; metal mediated catalysis of H₂O₂ originates the strongly reactive hydroxyl radical (HO^•). When targeting biomolecules, the three oxidants, as well as many other resulting from the catalytic action of xanthine oxidase, cyclooxygenases and lipoxygenases, nitric oxide synthase, norepinephrine breakdown and autoxidation processes, enlarge the diversity of oxidants and cause biomolecule damage (reviewed in ref. [43])