Reserve cells in human uterine cervical epithelium are derived from müllerian epithelium at midgestational age

The role of endocervical reserve cells in squamous metaplasia and neoplasia is still debated. Their origin in the cervix is open to speculation and it is unclear how they are targeted during carcinogenesis. To further understand the primary characteristics of reserve cells, we phenotyped them in the developing human cervix. In 13 perinatal autopsies of fetuses between 16 and 40 weeks of gestation, the human fetal cervix was evaluated in serial sections. Immunostaining comprised a panel of antibodies for cytokeratins, p63, and bcl-2; then, the sections were stained with Alcian blue and periodic acid-Schiff before and after diastase treatment. Reserve cells are first identified at approximately 20 weeks of gestation. They are first noted under müllerian-type columnar cells lining the developing uterine cavity. There is considerable overlap in the expression profiles of müllerian cells and reserve cells for p63, bcl-2, and cytokeratins 5, 8, and 18 at this stage of development, with increasing gestational age expression localized to respective cell compartments. Eventually, the phenotype of these cells correspond fully with that described for adult reserve cells and endocervical cells. Müllerian epithelial cells are the stem cell for endocervical reserve cells and endocervical columnar cells. They have the capacity to transform into both endocervical columnar and squamous-type epithelium in the endocervix during early cervical development.