OVARIAN INTRABURSAL ADMINISTRATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS FOLLICLE RUPTURE IN GONADOTROPIN-PRIMED MICE

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.