Sc. Juneja et al., OVARIAN INTRABURSAL ADMINISTRATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS FOLLICLE RUPTURE IN GONADOTROPIN-PRIMED MICE, Biology of reproduction, 55(6), 1996, pp. 1444-1451
We hypothesized that over-expression and/or activation of latent trans
forming growth factor beta s (TCF beta s) by various ovarian cell type
s may lead to disturbances in ovulation and fertilization. To test thi
s hypothesis, active TGF beta ranging from 1 to 500 ng was administere
d intrabursally into the ovaries of gonadotropin-primed mice, and the
rates of ovum recovery and fertilization were determined. Furthermore,
the presence and cellular distribution of endogenous TGF beta s and T
GF beta type I and type II receptors were determined immunohistochemic
ally in the ovarian tissues of TCF beta 1-treated and untreated groups
. The total number of ova recovered per ovary from ovaries treated as
pairs or treated singly with TGF beta 1 at 1 or 10 ng/ovary was simila
r to that from controls, whereas the number recovered from ovaries tre
ated as pairs or singly with 50 or 100 ng of TGF beta 1 per ovary was
significantly lower than the number from respective controls (p < 0.05
, 0.001). The number of ova recovered per ovary from ovaries treated a
s pairs or singly with TGF beta 1 at 200 or 500 ng/ovary was similar t
o the number of ova obtained from ovaries treated with TGF beta 1 at 1
00 ng/ovary. The rate of in vitro fertilization was low in ova recover
ed from ovaries treated with 50, 100, 200, and 500 ng/ovary of TCF bet
a 1, compared to that in ova from untreated ovaries. Histologically, t
he TGF beta 1-treated ovaries contained large numbers of unruptured fo
llicles, whereas untreated ovaries contained large numbers of corpora
lutea. Immunohistochemically, the endogenous TGF beta 1 and TGF beta 2
was localized in theca, granulosa, and luteal cells, without a substa
ntial difference in intensity or distribution, in both TGF beta 1-trea
ted ovaries and in controls. Theca cells were the primary site of immu
noreactive TGF beta protein. TGF beta type I and II receptors were als
o present in these cells, and their relative immunoreactive intensity
was considerably reduced, particularly in granulosa cells in TGF beta
1-treated ovaries compared to controls. The results support our hypoth
esis and suggest that TGF beta s play an important regulatory role in
follicular development, oocyte maturation, and the ovulatory process.