Leukemia inhibitory factor enhances bovine oocyte maturation and early embryo development

The present study was conducted to examine the effects of leukemia inhibitory factor (LIF) on bovine oocyte maturation and early embryo development in vitro. Results showed that LIF supplementation (25 ng/ml) enhanced nuclear maturation of intact cumulus-oocyte complexes (COCs) compared to the vehicle control. Similar results were observed in denuded oocytes, indicating that LIF directly influences oocyte development. LIF-treated oocytes showed a higher cortical-granule-migration rate and increased expression of CD9, a tetraspanin transmembrane protein essential for fertilization. After in vitro fertilization, oocytes receiving LIF supplementation exhibited a higher cleavage rate and yielded a significantly higher number of blastocysts. To further dissect the molecular mechanism underlying this LIF-induced bovine oocyte maturation phenotype, we examined the involvement of two signaling cascades, mitogen-activated protein kinases (MAPK3/1)- and the signal transducer and activator of transcription 3 (STAT3)-dependent pathways. Western blot results revealed that LIF phosphorylated MAPK3/1 and STAT3. Inhibition of MAPK3/1 activation with MEK inhibitor U0126 only partially blocked LIF-induced nuclear maturation, although it attenuated oocyte cytoplasmic maturation. Inhibition of JAK/STAT3 activation with a specific pharmacological inhibitor completely abolished the LIF-response in bovine oocyte. In summary, these data revealed a novel role for LIF in bovine oocyte maturation subsequent embryonic development.