The ultrastructure of resisting human female mammary gland epithelium was studied in 21 females of reproductive age (15–36 years) with regular menstrual cycles. Grossly and light microscopically normal appearing breast tissue contiguous to benign lesions was selected and processed at the time of frozen section diagnosis. Acino‐ductular epithelium was ultrastructurally classifiable into two major categories: Phase I—non‐secretory, and Phase II—potentially secretory. The above cells were often further classifiable into Phase IA cells, whose main feature was prominent intracellular fluid retention, and Phase IIA epithelium, characterized by cytoplasmic glycogen deposits. The preovulatory phase of the menstrual cycle was associated with a peak number of Phase I cells, while in the postovulatory phase there was a preponderance of Phase II cells. In the late preovulatory phase, Phase IA cells, and in the early postovulatory phase, Phase IIA cells were more commonly found. The relationship between the menstrual stage and cyclic changes in the ultrastructural morphology of mammary gland epithelium presumably represents the effects of ovarian steroid activity on the cellular physiology of an endocrine‐sensitive end organ; this is a cell biological phenomenon parallel to the better known cyclic cellular alterations occurring in the endometrium during the normal menstrual cycle. An understanding of the cyclic ultrastructural changes of mammary gland epithelium may lay the basis for a sounder and more meaningful interpretation of breast pathology and its pathogenesis.
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