Human Reproduction, Vol 13, 1133-1138, Copyright © 1998 by Oxford University Press
K Oktay, H Newton, J Mullan and RG Gosden
In contrast to the many detailed studies of Graafian follicles, the biology
of small follicles in the human ovary is poorly understood and the trigger
for follicular growth initiation remains unknown. No practical model exists
to study preantral follicle growth in the human because of their slow
growth rate and lack of an effective culture system. We therefore tested
ovarian xenografts as a new strategy to study the early stages of ovarian
follicular growth in vivo. Mice homozygous for severe combined
immunodeficiency (SCID) and hypogonadism (hpg) received human ovarian
xenografts under their kidney capsules. Follicle growth was assessed by
morphology and proliferating cell nuclear antigen (PCNA) immunostaining.
The grafts were recovered after 11 (short-term) and 17 weeks (long-term),
and serially sectioned. During the last 6 weeks of long-term grafting, mice
were randomized to receive either placebo or 1 IU of purified follicle
stimulating hormone (FSH) s.c. on alternating days. After 11 weeks of
grafting, the most advanced follicles had a maximum of two granulosa cell
layers. In the absence of FSH administration, follicles did not progress
beyond the two-layer stage even after 17 weeks of grafting, and the
oestradiol levels remained undetectable. In the FSH-treated long-term
grafts, follicles had grown to antral stages and resulted in oestradiol
levels as high as 2070 pmol/l. Growth initiation indices did not differ
between control and FSH-treated grafts. This study demonstrates that
follicles can survive and grow in human ovarian tissue grafted under the
renal capsules of immunodeficient mice for at least 17 weeks, and indicate
that xenograft models are potentially useful for studying human follicle
development. Using this physiological model, we showed that FSH is required
for follicle growth beyond the two-layer stage, although growth initiation
is independent of gonadotrophin stimulation.
ARTICLES
Development of human primordial follicles to antral stages in SCID/hpg mice stimulated with follicle stimulating hormone
Centre for Reproduction, Growth & Development, School of Medicine, University of Leeds, West Yorkshire, UK.
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