The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

COBL: The regulator of microvillar length in uterine epithelial cells (#375)

Samson Dowland , Chad Moore , Laura Lindsay , Christopher Murphy

During early pregnancy the luminal uterine epithelial cells (UECs) are extensively remodelled, where the microvilli are lost from the apical plasma membrane to enable interaction with the blastocyst. Microvilli are also dramatically altered in the rat model of ovarian hyperstimulated (OH) pregnancy. At the time of implantation in OH pregnancy microvilli are more numerous and longer than all stages of normal pregnancy, which is suggested to inhibit blastocyst implantation.

These dynamic changes in microvilli are unique to UECs, however the underlying molecular mechanisms driving the growth and retraction of these microvilli are currently unknown.

The present study has investigated the actin nucleation factor “Cordon-Bleu” (COBL) in UECs. COBL has recently been discovered to control the growth of microvilli in enterocytes. In these cells COBL is recruited to the base of microvilli, where it regulates the length of microvilli through its actin nucleation and severing abilities.

At the time of fertilisation in normal and OH pregnancy, UECs possess regular microvilli supported by an actin terminal web. COBL is concentrated at the base of these microvilli, associated with the terminal web. At the time of implantation during normal pregnancy, correlated light and electron microscopy (CLEM) demonstrates that UECs lose microvilli and the terminal web becomes disorganised. COBL remains localised to the region of the terminal web, where it may sever actin microfilaments to reduce the length of microvilli.

However, during OH pregnancy COBL is lost from UECs and CLEM indicates the unusually large, branching microvilli are not supported by an actin terminal web.

This study demonstrates for the first time that COBL is localised to the base of microvilli in UECs. During normal pregnancy, COBL may regulate the length of microvilli. However, the abnormal microvilli present during OH pregnancy do not appear to be associated with COBL or an actin terminal web.