Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide-treated prepubertal mice.
OBJECTIVE
To evaluate whether administration of goserelin, a gonadotropin-releasing hormone (GnRH) agonist, could prevent acute or chronic ovarian insufficiency from cyclophosphamide (CTX) administration to prepubertal mice.


METHODS
Animal study.


METHODS
University center.


METHODS
C57BL/6J mouse strain.


METHODS
Goserelin administered on day 13 of life, CTX on day 18 of life, euthanasia on day 20 (prepubertal), 56 (pubertal), or 92 of life (mature), measurements of body weight, length, uterine weight, serum antimüllerian hormone and follicle-stimulating hormone, and histologic assessment of ovarian follicles and femur growth, and apoptotic rates by TUNEL.


METHODS
Assessment of prevention of ovarian insufficiency and defective bone elongation from CTX administration.


RESULTS
Prepubertal mice were randomly assigned to three groups: control (G1), CTX (G2), and goserelin + CTX (GG). A total of 63 mice were euthanized in the three groups. Body weight and length, and uterine weight did not differ among groups at any age. Ovarian size was not different in the three groups. There were fewer primordial and primary follicles/mm(2) in groups GG and G2 than in group G1 at all ages, but there was no difference between groups GG and G2. Corpora lutea/mm(2) were decreased in group GG versus G2. Femur length was statistically significantly greater in groups G1 and GG than group G2.


CONCLUSIONS
Goserelin administered to prepubertal mice during CTX treatment fosters maintenance of bone elongation but does not protect the ovaries from follicular depletion.
Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tennessee. Electronic address: ldetti@uthsc.edu.
Laura
L
Detti
Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tennessee.
Rebecca A
RA
Uhlmann
Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee.
Jie
J
Zhang
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
Michael P
MP
Diamond
Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
Ghassan M
GM
Saed
Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
Nicole M
NM
Fletcher
Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee.
Meifen
M
Lu
Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tennessee.
Lucy J
LJ
Williams
D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D001846:Bone Development; D003520:Cyclophosphamide; D004347:Drug Interactions; D005260:Female; D017273:Goserelin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology*; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D011627:Puberty; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D017273:Goserelin; D003520:Cyclophosphamide
Cyclophosphamide; GnRH-analogues; goserelin; mice; ovary development; prepubertal