Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigativetool
D. Meirow et al., Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigativetool, HUM REPR, 14(7), 1999, pp. 1903-1907
Studies have shown that ovarian failure is a common side-effect of chemothe
rapy treatment; however, continuation of regular menses post-treatment does
not necessarily imply that the ovaries have escaped damage. This animal st
udy measures directly the primordial follicle (PMF) loss following exposure
to chemotherapy and evaluates reproductive outcome following significant d
estruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were ad
ministered different doses of an alkylating agent, cyclophosphamide, and th
e total number of PMF remaining in both ovaries was counted. Results show t
hat cyclophosphamide causes PMF destruction in proportion to increasing dos
e (P = 0.0001). Reproductive performance was assessed after exposure to 75
mg/kg cyclophosphamide, a dose which destroys similar to 50% of PMF reserve
, by evaluation of ovulation, mating and pregnancy rates. Reproductive pote
ntial of treated mice was not affected compared with controls despite the s
ignificant loss of PMF. Our results indicate that reproductive performance
is not an accurate parameter for assessing ovarian injury. Rather, histolog
ical counting of PMF number more directly reflects the damage caused by che
motherapy to the ovary. This method can be used as a sensitive, inexpensive
tool to gauge the damage to fertility caused by new chemotherapy agents or
protocols.