A Longitudinal Study of Estrous Cyclicity in Aging C57BL/6J Mice: I. Cycle Frequency, Length and Vaginal Cytology1

Abstract

Cycle frequency, length and vaginal cytology were measured longitudinally in 3 cohorts of singly housed virgin mice staggered across a 3-yr interval. The age profiles of these parameters were qualitatively similar, but quantitatively different, among cohorts. Cycle frequency was initially low (Phase I) due to prolonged cycles and late-starting cyclers, and did not peak (Phase II) until mice were 3-5 mo. old. Phase II lasted for 7-10 mo., depending on the cohort. Thereafter cycle frequency declined steadily (Phase III). The average age of cessation of cyclicity varied among cohorts, occurring between 13 and 16 mo. of age. Age changes in cycle length paralleled those of cycle frequency. During Phase II, median cycle length was < 5 days and variance was lowest. During Phases I and III, variance was about 2-fold greater and median cycle length was > 5 days. Although median cycle length remained stable for several months during Phase II, the peak period of 4-day cycles was much shorter. In all cohorts, 4-day cycles did not peak until 7-8 mo. of age and began to decline by 9 mo. The decrease in 4-day cycles was associated with a progressive lengthening of cycles-first from 4 to 5 days, then to longer cycles. The fraction of cycles with extended cornification (> 2 days) increased with advancing age from < 0.35 during the initial period of cycle lengthening to a maximum of 0.60. The observation that the initial phase of cycle prolongation is not usually associated with extended cornification is consistent with earlier evidence that this period is characterized by a delayed, rather than prolonged, preovulatory rise of estradiol. The increased fraction of prolonged cycles with extended cornification at later ages suggests that the preovulatory elevation of estradiol may ultimately be prolonged.