Hyaluronan– CD44 Signalling Contributes to Gap Junction Closure and LH Receptor Expression During In Vitro Maturation of Porcine Cumulus–Oocyte Complexes

Meiotic resumption in most mammals is triggered by luteinising hormone (LH), and an early event in this process is the disruption of gap junctional communication, which terminates the supply of cyclic adenosine monophosphate (cAMP) from cumulus cells to the oocyte. Cumulus expansion is driven by formation of a hyaluronan-rich extracellular matrix in cumulus-oocyte complexes (COCs) during oocyte maturation. Although we previously showed that hyaluronan plays an important role in nuclear maturation of oocytes, the mechanism by which hyaluronan regulates oocyte maturation remains unclear. Therefore, we hypothesised that hyaluronan contributes to gap junction closure within COCs to facilitate oocyte maturation. To test this hypothesis, we inhibited hyaluronan synthesis or the interaction between hyaluronan and its receptor, CD44, during porcine oocyte maturation. The inhibition attenuated the decline in intra-oocyte cAMP during in vitro maturation and, consistent with this, maintained gap junctional communication in COCs (as assessed by fluorescent dye transfer) and reduced tyrosine phosphorylation of connexin 43, the major gap junction protein expressed in COCs. In addition, hyaluronan was associated with LH receptor expression in COCs. Collectively, these results suggest that hyaluronan during cumulus expansion may act in concert with LH to support meiotic resumption during in vitro maturation of COCs, at least in part by contributing to gap junction closure.