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.

Efficient generation of bone morphogenetic protein 15-edited Yorkshire pigs using CRISPR/Cas9†

2020 ◽  
Vol 103 (5) ◽  
pp. 1054-1068
Author(s):  
Xuan Shi ◽  
Tao Tang ◽  
Qiyuan Lin ◽  
Hongbo Liu ◽  
Yufeng Qin ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Follicular Development ◽  
Female Fertility ◽  
Efficient Generation ◽  
Morphogenetic Protein ◽  
Yorkshire Pigs ◽  
Bone Morphogenetic Protein 15 ◽  
Ovarian Follicular Development

Abstract Bone morphogenetic protein 15 (BMP15), a member of the transforming growth factor beta superfamily, plays an essential role in ovarian follicular development in mono-ovulatory mammalian species. Studies using a biallelic knockout mouse model revealed that BMP15 potentially has just a minimal impact on female fertility and ovarian follicular development in polyovulatory species. In contrast, our previous study demonstrated that in vivo knockdown of BMP15 significantly affected porcine female fertility, as evidenced by the dysplastic ovaries containing significantly decreased numbers of follicles and an increased number of abnormal follicles. This finding implied that BMP15 plays an important role in the regulation of female fertility and ovarian follicular development in polyovulatory species. To further investigate the regulatory role of BMP15 in porcine ovarian and follicular development, here, we describe the efficient generation of BMP15-edited Yorkshire pigs using CRISPR/Cas9. Using artificial insemination experiments, we found that the biallelically edited gilts were all infertile, regardless of different genotypes. One monoallelically edited gilt #4 (Δ66 bp/WT) was fertile and could deliver offspring with a litter size comparable to that of wild-type gilts. Further analysis established that the infertility of biallelically edited gilts was caused by the arrest of follicular development at preantral stages, with formation of numerous structurally abnormal follicles, resulting in streaky ovaries and the absence of obvious estrous cycles. Our results strongly suggest that the role of BMP15 in nonrodent polyovulatory species may be as important as that in mono-ovulatory species.

scholarly journals Activation of both transforming growth factor-β and bone morphogenetic protein signalling pathways upon traumatic brain injury restrains pro-inflammatory and boosts tissue reparatory responses of reactive astrocytes and microglia

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Georgios Divolis ◽  
Athanasios Stavropoulos ◽  
Maria Manioudaki ◽  
Anastasia Apostolidou ◽  
Athanasia Doulou ◽  
...  
Keyword(s):  
Brain Injury ◽  
Growth Factor ◽  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Reactive Astrocytes ◽  
Glia Cells ◽  
Morphogenetic Protein

Abstract Various ligands and receptors of the transforming growth factor-β superfamily have been found upregulated following traumatic brain injury; however, the role of this signalling system in brain injury pathophysiology is not fully characterized. To address this, we utilized an acute stab wound brain injury model to demonstrate that hallmarks of transforming growth factor-β superfamily system activation, such as levels of phosphorylated Smads, ligands and target genes for both transforming growth factor-β and bone morphogenetic protein pathways, were upregulated within injured tissues. Using a bone morphogenetic protein-responsive reporter mouse model, we showed that activation of the bone morphogenetic protein signalling pathway involves primarily astrocytes that demarcate the wound area. Insights regarding the potential role of transforming growth factor-β superfamily activation in glia cells within the injured tissues were obtained indirectly by treating purified reactive astrocytes and microglia with bone morphogenetic protein-4 or transforming growth factor-β1 and characterizing changes in their transcriptional profiles. Astrocytes responded to both ligands with considerably overlapping profiles, whereas, microglia responded selectively to transforming growth factor-β1. Novel pathways, crucial for repair of tissue-injury and blood–brain barrier, such as activation of cholesterol biosynthesis and transport, production of axonal guidance and extracellular matrix components were upregulated by transforming growth factor-β1 and/or bone morphogenetic protein-4 in astrocytes. Moreover, both ligands in astrocytes and transforming growth factor-β1 in microglia shifted the phenotype of reactive glia cells towards the anti-inflammatory and tissue reparatory ‘A2’-like and ‘M0/M2’-like phenotypes, respectively. Increased expression of selected key components of the in vitro modulated pathways and markers of ‘A2’-like astrocytes was confirmed within the wound area, suggesting that these processes could also be modulated in situ by the integrated action of transforming growth factor-β and/or bone morphogenetic protein-mediated signalling. Collectively, our study provides a comprehensive comparative analysis of transforming growth factor-β superfamily signalling in reactive astrocytes and microglia and points towards a crucial role of both transforming growth factor-β and bone morphogenetic protein pathways in modulating the inflammatory and brain injury reparatory functions of activated glia cells.

scholarly journals Expression and biological effects of bone morphogenetic protein-15 in the hen ovary

2007 ◽  
Vol 194 (3) ◽  
pp. 485-497 ◽  
Author(s):  
S Elis ◽  
J Dupont ◽  
I Couty ◽  
L Persani ◽  
M Govoroun ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor ◽  
Biological Effects ◽  
Regulatory Protein ◽  
Transforming Growth Factor Β ◽  
Inhibitory Effect ◽  
Female Fertility ◽  
Follicular Maturation ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 15

The bone morphogenetic protein 15 (Bmp15) and growth differentiation factor 9 (Gdf9) genes are two members of the transforming growth factor-β superfamily. In mammals, these genes are known to be specifically expressed in oocytes and to be essential for female fertility. However, potential ovarian roles of BMPs remain unexplored in birds. The aim of the present work was to study for the first time the expression of Bmp15 in the hen ovary, to compare its expression pattern with that of Gdf9, and then to investigate the effects of BMP15 on granulosa cell (GC) proliferation and steroidogenesis. We found that chicken Bmp15 and Gdf9 genes were preferentially expressed in the ovary. We showed using in situ hybridization that Bmp15 and Gdf9 mRNAs were specifically localized in oocytes of all ovarian follicles examined. We also demonstrated using real-time quantitative RT-PCR that Bmp15 and Gdf9 expression was maintained during hierarchical follicular maturation in the gerrminal disc region and then progressively declined after ovulation. BMP15 was able to activate Smad1 (mothers against decapentaplegichomolog1) signaling pathway in hen GCs. Moreover, we showed a strong inhibitory effect of BMP15 on gonadotropin-induced progesterone production in hen GCs. This inhibitory effect was associated with a decrease in steroidogenic acute regulatory protein (STAR) level. Taken together, our results suggest that BMP15 may have a key role in the female fertility of birds.

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