scholarly journals 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

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 115-129 ◽  
Author(s):  
Francois Paradis ◽  
Susan Novak ◽  
Gordon K Murdoch ◽  
Michael K Dyck ◽  
Walter T Dixon ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Follicular Development ◽  
Transforming Growth Factor Β ◽  
Pcr Analysis ◽  
Temporal Regulation ◽  
Theca Cells ◽  
Follicular Wave ◽  
Morphogenetic Protein ◽  
Preovulatory Follicles ◽  
Ovulatory Process

This study aimed to describe the abundance and localization ofBMP2,BMP6,BMP15,GDF9,BMPR1A,BMPR1B,BMPR2andTGFBR1mRNA during pig preovulatory follicular development and to evaluate their implication in improving follicular maturity in the preovulatory period preceding the second versus first post-weaning oestrus. Oocytes, granulosa (GC) and theca cells (TC) were recovered from antral follicles of primiparous sows at day 1, 2 and 4 after weaning and at day 14, 16 and 20 of their subsequent oestrous cycle. Real-time PCR analysis revealed that with the exception ofBMP6mRNA, which was absent in GC, all genes were expressed in every cell type. AlthoughBMP6,BMP15andGDF9mRNA were most abundant in the oocyte, their expression remained relatively constant during follicular development. By contrast, receptorBMPR1BandTGFBR1expressions in the GC and TC were temporally regulated.BMPR1BmRNA abundance was positively correlated with plasma oestradiol (E2) suggesting that its regulation by oestrogen may be implicated in normal folliculogenesis. Interestingly, the increase inBMPR1BmRNA and protein abundance during the periovulatory period in GC and TC suggests a role for bone morphogenetic protein (BMP) 15 in the ovulatory process. Finally, expression of these ligands and receptors was not associated with potential differences in follicle maturity observed during the second versus first post-weaning preovulatory follicular wave. In conclusion, our results clearly demonstrate the presence of a complex signalling system within the pig follicle involving the transforming growth factor-β superfamily and their receptors, and provide evidence to support a role for BMP15 and BMPR1B during ovulation.

Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare

2015 ◽  
Vol 27 (6) ◽  
pp. 897 ◽  
Author(s):  
Juliano C. da Silveira ◽  
Quinton A. Winger ◽  
Gerrit J. Bouma ◽  
Elaine M. Carnevale
Keyword(s):  
Growth Factor ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Transforming Growth Factor ◽  
Follicular Development ◽  
Transforming Growth Factor Β ◽  
Follicle Development ◽  
Oocyte Competence ◽  
Age Related ◽  
Preovulatory Follicles

Age-related decline in fertility is a consequence of low oocyte number and/or low oocyte competence resulting in pregnancy failure. Transforming growth factor (TGF)-β signalling is a well-studied pathway involved in follicular development and ovulation. Recently, small non-coding RNAs, namely microRNAs (miRNAs), have been demonstrated to regulate several members of this pathway; miRNAs are secreted inside small cell-secreted vesicles called exosomes. The overall goal of the present study was to determine whether altered exosome miRNA content in follicular fluid from old mares is associated with changes in TGF-β signalling in granulosa cells during follicle development. Follicular fluid was collected at deviation (n = 6), mid-oestrus (n = 6) and preovulation (n = 6) for identification of exosomal miRNAs from young (3–12 years) and old (20–26 years) mares. Analysis of selected TGF-β signalling members revealed significantly increased levels of interleukin 6 (IL6) in granulosa cells from mid-oestrus compared with preovulatory follicles, and collagen alpha-2(I) chain (COL1A2) in granulosa cells from deviation compared with preovulatory follicles in young mares. In addition, granulosa cells from old mares had significantly altered levels of DNA-binding protein inhibitor ID-2 (ID2), signal transducer and activator of transcription 1 (STAT1) and cell division cycle 25A (CDC25A). Finally, changes in exosomal miRNA predicted to target selected TGF-β members were identified.

scholarly journals GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone

2020 ◽  
Vol 117 (9) ◽  
pp. 4910-4920 ◽  
Author(s):  
Joonho Suh ◽  
Na-Kyung Kim ◽  
Seung-Hoon Lee ◽  
Je-Hyun Eom ◽  
Youngkyun Lee ◽  
...  
Keyword(s):  
Bone Mass ◽  
Muscle Mass ◽  
Transforming Growth Factor ◽  
Bone Fractures ◽  
Muscle Growth ◽  
Transforming Growth Factor Β ◽  
Biochemical Properties ◽  
Bmp Signaling ◽  
Morphogenetic Protein ◽  
Perinatal Lethality

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality ofGdf11null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show thatGdf11null mice, despite significantly down-regulatingMstnexpression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed inMstnnull mice that display enhanced bone mass. Mechanistically,Mstndeletion up-regulatesGdf11expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlikeMstnnull mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.

Abstract 19602: Characterization of Tgfβ/BMP-axis in Multiple Animal Models of PH

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Chris Happé ◽  
Nina Rol ◽  
Denielli Da Silva Goncalves Bos ◽  
Cathelijne van der Bruggen ◽  
Anton Vonk-Noordegraaf ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Animal Models ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Downstream Signaling ◽  
Protein Levels ◽  
Morphogenetic Protein ◽  
Cardiac Adaptation ◽  
Bmp Pathway ◽  
Β Receptor

Introduction: Mutations in the bone morphogenetic protein recptor type 2 (BMPR2) comprise a large portion of familial Pulmonary Arterial Hypertension (PAH) cases. The transforming growth factor-β (TGF-β)/BMP-axis in PAH has been of interest, which is hypothesized to favor TGF-β signaling due to defective BMPR2 signaling, consequently leading to pro-proliferative signaling within the lung. In addition, it has been proposed that the BMPRII mutations might affect cardiac adaptation. To date none of the available animal models have been fully characterized with regard to the TGF-β/BMP pathway. This study assessed the lung and heart TGF-β/BMP-axis in multiple rat animal models of pulmonary hypertension to ensure translational capability. Methods: Heart and lung TGF-β/BMP-axis was assessed by qPCR, western blot and immunofluorescence in the the monocrotaline (MCT), Sugen-hypoxia (SuHx), Sugen-Pneumonectomy (SuPnx) and Pulmonary artery banding model (PAB) and compared to control and PAH patient tissues. Circulating ligands, TGF-β receptor (TGFβR) type 1 and 2 and BMPR2, and canonical downstream signaling (Smad2/3, Smad1/5/8, and transcription factors) were investigated. Results: BMPR2 was down-regulated at both transcription and protein levels in the lung of all PH animal models (p<0.05). Transcription of pulmonary TGFβR1 and -2 were increased in the SuPNx-model, compared to control (P<0.001). In both SuHx and SuPnx models an increase in protein Smad2/3 expression was observed by immunofluorescence implying overactivation of TGF-β signaling. Cardiac TGFβR1 was decreased in PAB model, compared to control (P<0.05), while TGFβR2 was decreased in both the MCT and PAB model. Conclusion: Early indications reveal differences between several pulmonary hypertension animal models, with regard to the TGF-β/BMP pathway. Additional analysis is needed to fully characterize the regulation of TGF-β and BMP in the rat models.

Effects of bone morphogenetic protein 15 (BMP15) knockdown on porcine testis morphology and spermatogenesis

2020 ◽  
Vol 32 (11) ◽  
pp. 999
Author(s):  
Tao Tang ◽  
Qiyuan Lin ◽  
Yufeng Qin ◽  
Xinyu Liang ◽  
Yang Guo ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Biological Function ◽  
Transforming Growth Factor Β ◽  
Reproductive Capacity ◽  
Ovary Development ◽  
Sperm Viability ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 15

Bone morphogenetic protein 15 (BMP15) is a member of the transforming growth factor-β (TGFB) superfamily that plays an essential role in mammalian ovary development, oocyte maturation and litter size. However, little is known regarding the expression pattern and biological function of BMP15 in male gonads. In this study we established, for the first time, a transgenic pig model with BMP15 constitutively knocked down by short hairpin (sh) RNA. The transgenic boars were fertile, but sperm viability was decreased. Further analysis of the TGFB/SMAD pathway and markers of reproductive capacity, namely androgen receptor and protamine 2, failed to identify any differentially expressed genes. These results indicate that, in the pig, the biological function of BMP15 in the development of male gonads is not as crucial as in ovary development. However, the role of BMP15 in sperm viability requires further investigation. This study provides new insights into the role of BMP15 in male pig reproduction.

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