Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-ß) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.

Phytomelatonin: assisting plants to survive and thrive.

This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots versus leaves, and with their developmental stage. As in animals, the pathway of melatonin synthesis in plants utilizes tryptophan as an essential precursor molecule. Melatonin synthesis is inducible in plants when they are exposed to abiotic stresses (extremes of temperature, toxins, increased soil salinity, drought, etc.) as well as to biotic stresses (fungal infection). Melatonin aids plants in terms of root growth, leaf morphology, chlorophyll preservation and fruit development. There is also evidence that exogenously-applied melatonin improves seed germination, plant growth and crop yield and its application to plant products post-harvest shows that melatonin advances fruit ripening and may improve food quality. Since melatonin was only discovered in plants two decades ago, there is still a great deal to learn about the functional significance of melatonin in plants. It is the hope of the authors that the current review will serve as a stimulus for scientists to join the endeavor of clarifying the function of this phylogenetically-ancient molecule in plants and particularly in reference to the mechanisms by which melatonin mediates its multiple actions.

Role of melatonin on production and preservation of gametes and embryos: a brief review.

The aim of this brief review is to clarify the role of melatonin in the production and preservation of mammalian gametes and embryos. Melatonin is an indoleamine synthesized from tryptophan in the pineal gland and other organs that operates as a hypothalamic-pituitary-gonadal axis modulator and regulates the waxing and waning of seasonal reproductive competence in photoperiodic mammals. A major function of the melatonin rhythm is to transmit information about the length of the daily photoperiod to the circadian and circannual systems in order to provide time-of-day and time-of-year information, respectively, to the organism. Melatonin is also a powerful antioxidant and anti-apoptotic agent, which is due to its direct scavenging of toxic oxygen derivatives and its ability to reduce the formation of reactive species. Mammalian gametes and embryos are highly vulnerable to oxidative stress due to the presence of high lipid levels; during artificial breeding procedures, these structures are exposed to dramatic changes in the microenvironment, which have a direct bearing on their function and viability. Free radicals influence the balance between oxidation-reduction reactions, disturb the transbilayer-phospholipid asymmetry of the plasma membrane and enhance lipid peroxidation. Melatonin, due to its amphiphilic nature, is undoubtedly useful in tissues by protecting them from free radical-mediated oxidative damage and cellular death. The supplementation of melatonin to semen extender or culture medium significantly improves sperm viability, oocyte competence and blastocyst development in vitro.

HDAC inhibition decreases XIST expression on female IVP bovine blastocysts.

During initial development, both X chromosomes are active in females, and one of them must be silenced at the appropriate time in order to dosage compensate their gene expression levels to male counterparts. Silencing involves epigenetic mechanisms, including histone deacetylation. Major X chromosome inactivation (XCI) in bovine occurs between hatching and implantation, although in vitro culture conditions might disrupt the silencing process, increasing or decreasing X-linked gene expression. In this study, we aimed to address the roles of histone deacetylase inhibition by trichostatin A (TSA) on female preimplantation development. We tested the hypothesis that by enhancing histone acetylation, TSA would increase the percentage of embryos achieving 16-cell stage, reducing percentage of embryos blocked at 8-cell stage, and interfere with XCI in IVF embryos. We noticed that after TSA treatment, acetylation levels in individual blastomeres of 8-16 cell embryos were increased twofold on treated embryos, and the same was detected for blastocysts. Changes among blastomere levels within the same embryo were diminished on TSA group, as low-acetylated blastomeres were no longer detected. The percentage of embryos that reached the 5th cleavage cycle 118 h after IVF, analyzed by Hoechst staining, remained unaltered after TSA treatment. Then, we assessed XIST and G6PD expression in individual female bovine blastocysts by quantitative real-time PCR. Even though G6PD expression remained unaltered after TSA exposure, XIST expression was eightfold decreased, and we also detected a major decrease in the percentage of blastocysts expressing detectable XIST levels after TSA treatment. Based on these results, we conclude that HDAC is involved on XCI process in bovine embryos, and its inhibition might delay X chromosome silencing and attenuate aberrant XIST expression described for IVF embryos.