Ovarian Intrabursal Administration of Transforming Growth Factor β1 Inhibits Follicle Rupture in Gonadotropin-Primed Mice1

Abstract

We hypothesized that over-expression and/or activation of latent transforming growth factor betas (TGF betas) by various ovarian cell types may lead to disturbances in ovulation and fertilization. To test this hypothesis, active TGF beta ranging from 1 to 500 ng was administered 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 betas and TGF beta type I and type II receptors were determined immunohistochemically in the ovarian tissues of TGF 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 to 10 ng/ovary was similar to that from controls, whereas the number recovered from ovaries treated 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 as pairs or singly with TGF beta 1 at 200 or 500 ng/ovary was similar to the number of ova obtained from ovaries treated with TGF beta 1 at 100 ng/ovary. The rate of in vitro fertilization was low in ova recovered from ovaries treated with 50, 100, 200, and 500 ng/ovary of TGF beta 1, compared to that in ova from untreated ovaries. Histologically, the TGF beta 1-treated ovaries contained large numbers of unruptured follicles, 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 substantial difference in intensity or distribution, in both TGF beta 1-treated ovaries and in controls. Theca cells were the primary site of immunoreactive TGF beta protein. TGF beta type I and type II receptors were also 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 hypothesis and suggest that TGF betas play an important regulatory role in follicular development, oocyte maturation, and the ovulatory process.

Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig

“…The expression of TGFBR1 mRNA has only been studied in antral follicles of mouse, sheep and cow ovaries, and, consistent with our findings, was expressed in the oocyte, GC and TC (Juneja et al 1996, Juengel et al 2004, Feary et al 2007). Similar to the observations made for the ligands in our study, the oocyte was found to abundantly express BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA but little variation in mRNA abundance was observed between the different time points.…”

SMAD3 regulates the diverse functions of rat granulosa cells relating to the FSHR/PKA signaling pathway

“…TGFb is an important growth factor, which regulates follicular growth, atresia, and maturation of the ovum (Liu et al 1999, Saragueta et al 2002. TGFb is considered to play a dual regulatory role in the function of GCs (Juneja et al 1996). As an important TGFb-activated downstream signaling transduction protein, SMAD3 is found in cultured GCs (Xu et al 2002).…”

Transforming growth factor-β: its role in ovarian follicle development

“…Tgfbr1 mRNA and protein are expressed by porcine granulosa cells (Goddard et al 1995), whilst TGFBR1 protein is expressed by mouse luteal cells, granulosa cells, theca cells and oocytes (Juneja et al 1996, Gueripel et al 2004). Tgfbr2 mRNA is present in rat ovary (Tsuchida et al 1993), whereas mRNA and protein have been localized to porcine granulosa cells (Goddard et al 1995) and mouse theca, granulosa cells, oocytes and luteal cells (Schmid et al 1994, Gueripel et al 2004.…”