The Inconstant Oviduct

During the estrous cycle, a rise in estrogen prior to ovulation alters the composition of the fluid in the oviduct to promote reproductive functions, according to a new study of this oftenoverlooked tissue [1]. As a result, embryos survive to travel successfully to the uterus. Many studies have established that estrogen helps mediate the receptivity of the uterine endometrium to implantation. Wipawee Winuthayanon et al. asked if estrogen similarly prepares the oviduct for reproductive events around ovulation, such as support of sperm movement and fertilization. To answer this question, the researchers examined mice with estrogen receptor a knocked out only in the epithelial cells of the uterus and oviduct. These mice had impaired fertilization due to a major reduction in the migration of sperm into the oviduct, possibly because of changes in fluid composition in the uterus—the knockout mice had changes in the levels of proteins thought to ‘‘liquefy’’ semen and facilitate sperm movement into the oviduct. The eggs that managed to become fertilized died in the oviduct before the two-cell-stage, the data suggest. The researchers next performed microarray analysis, and found that the expression of numerous secreted factors—many involved in immune function—seemed to be altered in the knockout mice. Also, there was also elevated activity of celldamaging proteases, which, it seems, harmed the zona pellucida and embryo. Wild-type embryos transferred into the oviducts of these mice did not develop normally, but the phenotype that could be rescued by the co-transfer of protease inhibitors did. The oviduct plays a tight balancing act, acting as a shield against pathogen invasion but also allowing for survival and passage of sperm, egg, and embryo. The data suggest that the spike in estrogen prior to ovulation quells the immune response to allow for reproductive functions in the oviduct. The new findings also have relevance for certain types of infertility—for instance, women with hydrosalpinges produce tubal fluid that can kill zygotes.