Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle

Abstract

Recent studies have demonstrated that bone morphogenetic proteins (BMPs) play fundamental roles in female fertility. This is particularly evident in terms of the ovary. One major question that is just beginning to be addressed is the role of BMPs in the non-pregnant uterus. To help fill this gap, we used in situ hybridization to investigate the expression of BMP family members in the rat uterus over the estrous cycle. We found that the endometrial/uterine cycle is accompanied by the expression of several components of the BMP pathway -including ligands, receptors and antagonists. The mRNAs encoding BMP receptors are expressed in the epithelial (BMP-RIA, -RIB and -RII), periluminal stroma (BMP-RIA and -RII) and smooth muscle cells (BMP-RIA and -RII). The expression of all three receptors showed clear cyclic variations. The mRNAs encoding BMP ligands were highly expressed in the periluminal stroma (BMP-2 and -7) and glandular epithelium (BMP-7). The expression of BMP-2, but not BMP-7, was cyclical. Notably, the periluminal stroma expressed noggin mRNA. In the blood vascular system, BMP-4, -6 and -RII mRNAs were expressed in myometrial endothelial cells. Interestingly, follistatin, noggin, and BMP-4, -6 and -7 mRNAs were expressed in eosinophilic leukocytes, suggesting unexpected roles for eosinophil-derived BMPs in uterine function. We conclude that BMP ligands, receptors and antagonists are expressed in spatially and temporally restricted patterns that are consistent with a physiological role for these regulatory molecules in promoting uterine cellular processes including cell proliferation, differentiation and apoptosis during the cycle.

Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin

“…There is evidence that both leptin and adiponectin receptors are expressed in the cumulus cells, and adiponectin receptors exhibit differential target gene expression profile in cumulus (CC) compared to granulosa cells (GC) [20,24]. One example of an interesting target gene is Bmp2, which has been implicated in follicular apoptosis and fetal germ cell differentiation in the ovary [6,10]. Adiponectin was found to upregulate the expression of Bmp2 in CCs [20], although whether the adiponectin Bmp2 interaction has a functional significance in vivo remains to be elucidated.…”

Testing the antagonistic effect of follistatin on BMP family members in ovine granulosa cells

“…Follicular cells of secondary to antral follicles have also been shown to express other various BMP factors, such as BMP-2, BMP-3, BMP-4 and BMP-7, concomitantly with follistatin [30][31][32]. In vitro experiments using recombinant BMP-2, BMP-4 or BMP-7 have designated these BMP, as well as oocyte-derived BMP, as anti-luteinizing factors [19,32,33].…”

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

“…Except a solitary report by Erickson & Shimasaki (2003) on rat, no study could be found on BMPs in the CL. To the best of our knowledge, this is the first study on BMP6 in the CL of riverine buffalo.…”

“…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).…”