Long-term ovarian and gonadotropin changes in mice exposed to 4-vinylcyclohexene.
This study investigated the relationships between 4-vinylcyclohexene-induced 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 plasma was collected for measurement of FSH. Ovarian weight was less and oocytes 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 and 360 days, small to medium, irregularly shaped foci of hypertrophic cells were present. In addition, at 360 days 80% of the VCH-treated mice had a 1- to 2-mm, blood-filled cystic structure present in one or both ovaries. These studies indicate that VCH-induced oocyte destruction and follicle loss are associated with increases in plasma FSH, are associated with ovarian failure at 360 days, and are temporally related to ovarian cellular hypertrophy and the formation of blood-filled cystic ovarian structures. These events are possibly related to ovarian neoplasms produced by long-term exposure to VCH.
Hooser
S B
SB
Department of Pharmacology and Toxicology, University of Arizona, College of Pharmacy, Tucson 85721.
Douds
D P
DP
DeMerell
D G
DG
Hoyer
P B
PB
Sipes
I G
IG
D000735:Androstenedione / Q000097:blood; D000818:Animals; D003510:Cyclohexanes / Q000633:toxicity*; D053138:Cyclohexenes; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006062:Gonadotropins / Q000097:blood*; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D011863:Radioimmunoassay; D014621:Vagina / Q000473:pathology
D003510:Cyclohexanes; D053138:Cyclohexenes; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; C013733:4-vinylcyclohexene; D000735:Androstenedione; D005640:Follicle Stimulating Hormone