Abstract:

Progesterone is a female sex hormone that is essential for successful establishment of pregnancy. Its level rises sharply following ovulation and is sustainably high during the uterine receptivity period, a time when the blastocyst implant. Under progesterone influence, several changes occur in the endometrium to ensure successful blastocyst implantation. These include changes to the uterine fluid microenvironment including reduce fluid volume as well as changes to its ionic composition. Studies have shown that these changes are mediated through the effect of progesterone on expression of ion transporters’ genes and proteins including its effect in upregulating the epithelial sodium channel (ENaC), sodium-potassium ATPase pump (Na⁺/K⁺-ATPase) and sodium-calcium exchanger (NCX), as well as in downregulating the expression of Cystic Fibrosis transmembrane regulator (CFTR), a chloride channel that is known to suppress the ENaC activity in endometrial luminal and glandular epithelium. Progesterone has also been found to upregulate the expression of gene and protein for aquaporin channel subunits AQP-5 and AQP-7 in the uterine luminal epithelium. This hormone might also increase the ENaC open channel probability which directly increases ENaC activity. The consequence of ENaC upregulation and increased ENaC activity would be increased Na⁺ reabsorption followed by water reabsorption from the uterine lumen, thus reduces the uterine fluid volume which will subsequently help to bring the blastocyst closer to the uterine luminal epithelium, initiating the attachment phase of blastocyst implantation. Meanwhile, increased Na⁺ reabsorption will also create a net positive charge in the uterine luminal epithelium that will attract the negatively charged blastocyst towards the uterine wall. Additionally, the efflux of Na⁺ from the uterine epithelium will trigger the influx of Ca²⁺ and subsequently will stimulate the intracellular Ca²⁺ release. Apart from this, progesterone has been found to trigger the release of Ca²⁺ from the intracellular stores, directly. Increased intracellular Ca²⁺ levels will activate the intracellular signalling pathways that initiate decidualization. In conclusion, progesterone is an essential hormone in early phase of blastocyst implantation and its deficiency would results in failure to establish clinical pregnancy.