Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age.
OBJECTIVE
AMH is used to quantify the extent of follicular pool in postpubertal women, but its value after chemotherapy is unclear. We tested AMH as a marker of follicular reserve in adult mice treated with cyclophosphamide (CTX) in prepubertal age.


METHODS
Mice received placebo or CTX at age 18 days. AMH and FSH were assessed on day 43, 56, and 95 of life. Ovaries were fixed in formalin, embedded in paraffin, and stained with H&E and TUNEL. Follicular apoptosis was graded.


RESULTS
All mice exposed to CTX had a decreased number of follicles/mm(2) and significantly decreased AMH, but only 48 % of pubertal and 81 % of adult mice had increased FSH. Over time, there was an increase in FSH (p < 0.05), but not a concurrent decrease in AMH, while in controls, FSH remained stable and AMH decreased. There was no correlation between histological and serological markers.


CONCLUSIONS
CTX administration to pre-pubertal mice caused various degrees of residual function, which were reflected by FSH, but not by AMH or by the number of ovarian follicles. AMH served as a marker of quantitative, and FSH of qualitative, residual ovarian function.
Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Rout Center, 853 Jefferson Ave, Room E102, Memphis, TN, 38163, USA, ldetti@uthsc.edu.
Laura
L
Detti
Rebecca A
RA
Uhlmann
Meifen
M
Lu
Michael P
MP
Diamond
Ghassan M
GM
Saed
Nicole M
NM
Fletcher
Jie
J
Zhang
Lucy J
LJ
Williams
D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood*; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood*; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D012741:Sexual Maturation / Q000187:drug effects*
D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D054304:Anti-Mullerian Hormone; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone