The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat

Abstract

The intraovarian roles of BMP family members such as BMP2, 4, 6 and 7 are not well understood, particularly in species with low ovulation rates such as sheep. Therefore, the objectives of these experiments were to determine the expression patterns of mRNAs encoding BMP2, 4, 6 and 7 during ovarian follicular development in sheep, and to determine the effects of these growth factors on ovine granulosa cell functions in vitro. For comparative purposes, the effects of these BMPs were also determined in rat granulosa cells since these factors have been most widely studied in this poly-ovulatory species. As assessed by in situ hybridization, non-atretic ovine follicles expressed mRNA for BMP6 but not 2, 4 or 7. Furthermore, expression of BMP6 was limited to the oocyte of primordial as well as primary, pre-antral and antral follicles. Reverse transcription-PCR of granulosa cell mRNA detected low levels of all the BMPs in some pools of cells. BMP2, 4, 6 and 7 each inhibited progesterone production from ovine granulosa cells without affecting cellular proliferation/survival. Similarly, these BMPs inhibited progesterone production from rat granulosa cells. However, they also stimulated cellular proliferation/survival of the rat granulosa cells highlighting a species-specific difference for these growth factors. In conclusion, in sheep, BMP2, 4, 6 and 7 inhibit granulosa cell differentiation without affecting proliferation. However, as BMP2, 4 and 7 were not detectable by in situ hybridization in any cells of non-atretic ovarian follicles, it seems unlikely that these proteins would have an important intraovarian role in regulating follicular development in sheep. In contrast, localization of BMP6 mRNA in the oocyte suggests that this BMP family member may have a paracrine and/or autocrine role in regulating follicular growth in sheep, as has been shown for two other oocyte derived from members of the transforming growth factor superfamily, BMP15 and growth differentiation factor 9.

Expression and localization of bone morphogenetic protein6 (BMP6) in the corpus luteum during different stages of estrous cycle in the buffalo (Bubalus bubalis)

“…In the ovary, investigations on BMPs are mainly studied in the follicle of rat (Erickson & Shimasaki, 2003), cow (Glister et al, 2010) and ewe (Juengel et al, 2006). Except a solitary report by Erickson & Shimasaki (2003) on rat, no study could be found on BMPs in the CL.…”

“…The mid CL showed a significantly increased expression of BMP6 transcripts ( Figure. 1), which is consistent with the results of western blot ( Figure. 2A and B) and immunofluorescence ( Figure. 3).Though BMP6 mRNA was highly expressed in the theca cells and the oocytes of rat (Erickson & Shimasaki, 2003) and cow (Glister et al, 2004), it was only expressed in oocytes in the follicle of ewe (Juengel et al, 2006). In bovine GCs, BMP6 upregulated basal and IGF stimulated Estrogen (E2) production (Glister et al, 2004).…”

Bone Morphogenetic Protein-6 (BMP-6) induces atresia in goat primordial follicles cultured in vitro

“…The BMP-6 protein is expressed in oocytes (ovine: Juengel et al 2006, murine: Otsuka et al 2001bovine: Glister et al 2004;porcine: Brankin et al 2005a), granulosa (murine: Erickson & Shimasaki 2003;bovine: Glister et al 2004;porcine: Brankin et al 2005a), and theca cells (ovine: Campbell et al 2004;bovine: Glister et al 2004) of ovarian follicles during different stages of development. As part of its biological function, BMP-6 forms heteromeric complexes with a type I and type II receptor.…”

“…In vitro studies have demonstrated that BMP-6 controls steroidogenesis as well as granulosa and theca cell proliferation in ovine (Juengel et al 2006) and porcine (Brankin et al 2005a). Juengel et al (2006) established that BMP-6 inhibits ovine granulosa cell differentiation.…”

“…Juengel et al (2006) established that BMP-6 inhibits ovine granulosa cell differentiation. In addition, BMP-6 is effective at inhibiting FSH-induced progesterone synthesis by murine granulosa cells, without affecting estradiol production .…”