Beneficial effects of brain-derived neurotropic factor on in vitro maturation of porcine oocytes

Abstract

In an effort to improve the quality of in vitro produced porcine embryos, we investigated the effect of brain-derived neurotropic factor (BDNF), a neurotropin family member, on in vitro maturation (IVM) of porcine oocytes. The expression of BDNF and truncated isoforms of its receptor, tyrosine kinase B (TrkB), and p75 common neurotropin receptor was detected in both follicular cells and metaphase-I stage oocytes by RT-PCR. However, mRNA of full-length TrkB was not found in oocytes although it was detected in follicular cells. The expression pattern of BDNF and TrkB was confirmed by immunohistochemistry. Supplementation with BDNF (30 ng/ml) during IVM significantly (P!0.05) increased the first polar body extrusion and glutathione levels in oocytes, whereas the effect of BDNF on nuclear maturation was diminished when gonadotropin and epidermal growth factor (EGF) were added to the culture media. However, treatment with BDNF (30 ng/ml) along with EGF (10 ng/ml) in the presence of gonadotropin significantly (P!0.05) increased the developmental competence of oocytes to the blastocyst stage after both in vitro fertilization (IVF; 29.1% when compared with control, 15.6%) and somatic cell nuclear transfer (SCNT; 13.6% when compared with control, 3%). This appeared to reflect a stimulatory interaction between BDNF and EGF to enhance the cytoplasmic maturation of oocytes to support successful preimplantation development. In conclusion, BDNF enhanced nuclear and cytoplasmic maturation of oocytes by autocrine and/or paracrine signals. Also, when used together with EGF, BDNF increased the developmental potency of embryos after IVF and SCNT, demonstrating an improved in vitro production protocol for porcine oocytes.

The roles of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and nerve growth factor during the final stage of folliculogenesis: a focus on oocyte maturation

“…However, contrary to the results observed in rodents, bovine NTRK2 mRNA was detected only in cumulus cells (Martins da Silva et al 2005). Porcine COCs express mRNA for BDNF and its receptors in both follicular somatic cells and oocytes, while NTRK2 was not detected in oocytes (Lee et al 2007). In women undergoing IVF, BDNF was present in follicular fluid, with the source of BDNF identified to be derived exclusively from cumulus cells, as neither cultured oocytes stripped of cumulus cells, mural granulosa cells or embryos released any appreciable levels of BDNF into the culture medium (Seifer et al 2002a).…”

“…However, in a recent study, it was shown that BDNF does significantly increase the percentage of bovine MII oocytes, while no statistically significant changes were recorded for its effect on development to the blastocyst stage (Hong et al 2009). As a potential candidate for improving in vitro culture and embryo production of porcine oocytes, inclusion of BDNF in the IVM medium significantly increased first polar body extrusion, as well as enhancing oocyte developmental competence to reach the blastocyst stage following IVF and somatic cell nuclear transfer (Lee et al 2007). In COCs derived from women undergoing laparoscopy who were then subjected to IVM, BDNF did not affect MII yields .…”

Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy

“…As discussed above, BDNF production in cumulus is known to be stimulated by LH/hCG, but its regulation by oocyte factors is unknown. BDNF has been reported to increase oocyte maturation to MII and developmental potential after parthenogenetic activation in mouse, cow and pig (Seifer et al 2002a, Kawamura et al 2005, Martins da Silva et al 2005, Lee et al 2007, but data in the human suggest a negative effect on oocyte developmental competence (Anderson et al 2009). Further experimental data are required to elaborate the nature of the interaction between BDNF and fertilisation, but the present data support the conclusion that BDNF may have an important role at this critical point.…”

Brain-derived neurotrophic factor from follicular fluid is positively associated with rate of mature ooocytes collected and cleavage rate in intracytoplasmic sperm injection patients

“…Treatment with BDNF during the in vitro maturation (IVM) of bovine oocytes could produce more parthenogenetic embryos, and the authors speculated BDNF could improve oocyte cytoplasm maturation [8]. This effect was also observed in porcine oocytes, which showed that BDNF could improve both nuclear and cytoplasmic maturation through autocrine and/or paracrine signal pathways [9]. One recent study demonstrated that BDNF could promote human oocyte maturation and early embryo development [10].…”