This study investigated the relationships between 4-vinylcyclohexene-i
nduced follicular destruction, plasma FSH levels, and the development
of ovarian preneoplastic changes. Female, 28-day-old, B6C3F1 mice were
administered VCH (800 mg/kg/day, ip) or sesame seed oil, ip daily for
30 days. At 30, 60, 120, 240, and 360 days following the beginning of
treatment, groups were killed, their ovaries were harvested, and plas
ma was collected for measurement of FSH. Ovarian weight was less and o
ocytes contained in preantral follicles were significantly fewer than
controls at all time points. Plasma FSH concentrations in VCH-treated
animals were increased significantly above controls at 240 d and 360 d
. Histologically, there was oocyte loss at all times, whereas at 240 a
nd 360 days, small to medium, irregularly shaped foci of hypertrophic
cells were present. In addition, at 360 days 80% of the VCH-treated mi
ce had a 1- to 2-mm, blood-filled cystic structure present in one or b
oth ovaries. These studies indicate that VCH-induced oocyte destructio
n and follicle loss are associated with increases in plasma FSH, are a
ssociated with ovarian failure at 360 days, and are temporally related
to ovarian cellular hypertrophy and the formation of blood-filled cys
tic ovarian structures. These events are possibly related to ovarian n
eoplasms produced by long-term exposure to VCH.