Human Reproduction, Vol 13, 664-669, Copyright © 1998 by Oxford University Press
J Smitz, R Cortvrindt and Y Hu
Using a mouse early preantral follicle culture system, mature full grown
oocytes, arrested in prophase I of meiosis, were produced after 12 days
using a recombinant gonadotrophin-supplemented medium. This culture medium
does not mimic the normal extracellular environment of the oocyte and might
therefore modify meiotic regulation and more particularly progression to
metaphase II (MII). The aim of this study was to optimize the treatment
using recombinant stimulatory ligands which were known to induce germinal
vesicle breakdown (GVBD) and completion of meiosis I, metaphase II (MII),
namely recombinant follicle stimulating hormone (r-FSH), chorionic
gonadotrophin (r-HCG) and epidermal growth factor (EGF). Full-grown
intrafollicular oocytes could not resume meiosis when the 'ovulatory'
stimulus was r-FSH, used at a 100 times higher dose than during culture.
r-FSH did not increase progesterone production. When 1.5 IU/ml r-HCG was
used as meiotic trigger, germinal vesicle breakdown was obtained in 95% of
the oocytes 64% of which extruded a first polar body. r-HCG induced a
dramatic increase in progesterone production. When EGF was administered as
sole stimulus on day 12 to the attached follicle-enclosed oocytes, only
doses > or =5 ng/ml could cause GVBD, although less effectively than r-
HCG (45 versus 95%; P < 0.0001). Oocytes undergoing GVBD by the EGF
pulse reached metaphase II at a rate of 54% (not significant versus r-
HCG). EGF did not stimulate progesterone production. Addition of increasing
doses of EGF (0.5; 5; 10; 50 ng/ml) to r-HCG did not increase the
GVBD-rate, but EGF doses >5 ng/ml improved MI to MII transition
(P=0.027), thereby improving the final yield of MII oocytes by 12.5%. These
data show that up to a dose of 50 ng/ml, EGF on its own could only override
the somatic inhibitory stimuli in less than half of the cultured follicles.
However, in addition to HCG, EGF (25 ng/ml) had a stimulatory effect on
completing the first meiotic division. It was concluded that, under the
present culture conditions, EGF in combination with HCG provided optimal
nuclear maturation.
ARTICLES
Epidermal growth factor combined with recombinant human chorionic gonadotrophin improves meiotic progression in mouse follicle-enclosed oocyte culture
Centre for Reproductive Medicine, University Hospital and Medical School, Dutch-speaking Brussels Free University, Belgium.
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