Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide treated prepubertal mice

Capsule:
Goserelin administration during prepubertal cyclophosphamide treatment fosters bone elongation but does not protect from ovarian follicular depletion.

Authors:
Laura Detti, M.D., Rebecca A. Uhlmann, M.S., Jie Zhang, M.D., Michael P. Diamond, M.D., Ghassan M. Saed, Ph.D., Nicole M. Fletcher, Ph.D., Meifen Lu, B.S., Lucy J. Williams, E.L.D.

Volume 101, Issue 4, Pages 1157-1164.e1

Abstract:

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.

Design:
Animal study.

Setting:
University center.

Animal(s):
C57BL/6J mouse strain.

Intervention(s):
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.

Main Outcome Measure(s):
Assessment of prevention of ovarian insufficiency and defective bone elongation from CTX administration.

Result(s):
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/mm2 in groups GG and G2 than in group G1 at all ages, but there was no difference between groups GG and G2. Corpora lutea/mm2 were decreased in group GG versus G2. Femur length was statistically significantly greater in groups G1 and GG than group G2.

Conclusion(s):
Goserelin administered to prepubertal mice during CTX treatment fosters maintenance of bone elongation but does not protect the ovaries from follicular depletion.

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