Transforming growth factor-β superfamily and interferon-τ in ovarian function and embryo development in female cattle: review of biology and application

2020 ◽  
Vol 32 (6) ◽  
pp. 539 ◽  
Author(s):  
Michael J. D'Occhio ◽  
Giuseppe Campanile ◽  
Pietro S. Baruselli
Keyword(s):  
Growth Factor ◽  
Embryo Development ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Reproductive Function ◽  
Transforming Growth Factor Β ◽  
Bovine Embryo ◽  
Primary Follicle ◽  
Embryo Survival ◽  
Female Cattle

Survival of the embryo and establishment of a pregnancy is a critical period in the reproductive function of female cattle. This review examines how the transforming growth factor-β (TGFB) superfamily (i.e. bone morphogenetic protein (BMP) 15, growth differentiation factor (GDF) 9, anti-Müllerian hormone (AMH)) and interferon-τ (IFNT) affect ovarian function and embryo development. The oocyte in a primary follicle secretes BMP15 and GDF9, which, together, organise the surrounding granulosa and theca cells into the oocyte–cumulus–follicle complex. At the same time, the granulosa secretes AMH, which affects the oocyte. This autocrine–paracrine dialogue between the oocyte and somatic cells continues throughout follicle development and is fundamental in establishing the fertilisation potential and embryo developmental competency of oocytes. The early bovine embryo secretes IFNT, which acts at the uterine endometrium, corpus luteum and blood leucocytes. IFNT is involved in the maternal recognition of pregnancy and immunomodulation to prevent rejection of the embryo, and supports progesterone secretion. Manipulation of BMP15, GDF9, AMH and IFNT in both invivo and invitro studies has confirmed their importance in reproductive function in female cattle. This review makes the case that a deeper understanding of the biology of BMP15, GDF9, AMH and IFNT will lead to new strategies to increase embryo survival and improve fertility in cattle. The enhancement of oocyte quality, early embryo development and implantation is considered necessary for the next step change in the efficiency of natural and assisted reproduction in cattle.

Genes of the transforming growth factor-beta signalling pathway are associated with pre-implantation embryonic development in cattle

2012 ◽  
Vol 79 (3) ◽  
pp. 310-317 ◽  
Author(s):  
Geng Li ◽  
Karam Khateeb ◽  
Erin Schaeffer ◽  
Bao Zhang ◽  
Hasan Khatib
Keyword(s):  
Growth Factor ◽  
Embryo Development ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Transforming Growth Factor Β ◽  
Fertilization Rate ◽  
Bovine Embryo ◽  
Altered Expression

One of the main factors affecting cattle fertility is pre-implantation development of the bovine embryo, which is a complex process regulated by various signal-transduction pathways. The transforming growth factor-β (TGF-β) signalling system, which is responsible for many biological processes including cell proliferation, differentiation and apoptosis, also is involved in embryo development. We hypothesized that altered expression of TGF-β genes in pre-implantation bovine embryos is associated with morphological abnormalities of these embryos. To test this hypothesis, we produced embryos in vitro and classified them at the blastocyst stage as either normally developed blastocysts or degenerates (growth-arrested embryos). The expression patterns of 25 genes from the TGF-β pathway were assessed using quantitative real time PCR. Ten genes showed differential expression between the two embryo groups, four genes displayed similar expressional profiles, and 11 genes had no detectable expression. An altered expression profile was statistically significant for 10 of the 14 expressed genes, and all were up-regulated in degenerate embryos vs. blastocysts. Furthermore, genomic association analysis of the cows from which embryos were produced revealed a significant association of ID3 and BMP4 polymorphisms—two of the most significant differentially expressed genes—with fertilization rate and blastocyst rate, respectively. Taken together, we conclude that TGF-β pathway genes, especially BMP4 and ID3 play a vital function in the regulation of pre-implantation embryo development at both embryo and maternal levels. Hence, these genes may be suitable as genetic markers for embryo development and fertility in cattle.

scholarly journals Cell-specificity of transforming growth factor-β response is dictated by receptor bioavailability

2006 ◽  
Vol 36 (3) ◽  
pp. 591-600 ◽  
Author(s):  
Magdalena I Suszko ◽  
Teresa K Woodruff
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reproductive Function ◽  
Transforming Growth Factor Β ◽  
Family Control ◽  
Cellular Processes ◽  
Relative Contribution ◽  
A Cell ◽  
Mouse Pituitary ◽  
And Migration

Members of the transforming growth factor-β (TGFβ) family control diverse cellular responses including differentiation, proliferation, controlled cell death and migration. The response of a cell to an individual ligand is highly restricted yet the signaling pathways for TGFβ, activin and bone morphogenic proteins share a limited number of receptors and activate similar intracellular cytoplasmic co-regulators, Smads. A central question in the study of this family of ligands is how cells titrate and integrate each TGFβ-like signal in order to respond in a cell- and ligand-specific manner. This study uses the pituitary gonadotrope cell line, LβT2, as a model to delineate the relative contribution of TGFβ and activin ligands to follicle-stimulating hormone (FSH) biosynthesis. It was found that pituitary gonadotrope cells do not express the TGFβ type II (TβRII) receptor and are therefore not responsive to the TGFβ ligand. Transfection of the receptor restores TGFβ signaling capabilities and the TGFβ-mediated stimulation of FSHβ gene transcription in LβT2 cells. Consequently, we evaluated the presence of the TβRII in the adult mouse pituitary. TβRII does not co-localize with FSH-producing cells; however it is detected on the cell surface of prolactin- and growth hormone-positive cells. Taken together, these results suggest that the bioavailability of the TGFβ-specific receptor rather than TGFβ dictates pituitary gonadotrope selectivity to activin, which is necessary to maintain normal reproductive function. It is likely that the ligand-restricted mechanisms employed by the gonadotrope are present in other cells, which could explain the distinct control of many cellular processes by members of the TGFβ superfamily.

267. A role for transforming growth factor-β 1 (TGF-β1) during the establishment of folliculogenesis

2008 ◽  
Vol 20 (9) ◽  
pp. 67
Author(s):  
I. Kuyznierewicz ◽  
J. K. Findlay ◽  
A. E. Drummond
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Cell Function ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Cyclin D2 ◽  
Tgf Β1

A group of structurally related proteins, known as the transforming growth factor-β (TGF- β) superfamily, have been implicated in the local regulation of ovarian function. It is unclear what role TGF-β1–3 plays in folliculogenesis during the period after birth in the rat. We investigated whether the TGF-β ligands and their receptors were present during this period of development and the effects of TGF-β1 on granulosa cell function (proliferation, apoptosis, steroidogenesis). Ovaries from rats 4, 8 and 12 days of age were isolated and RNA extracted and reverse transcribed for real-time PCR. The expression of the TGF-β ligands and TGFβRI and TGFβRII were measured. Granulosa cells isolated from DES treated immature rats were treated with FSH (100ng/mL) and TGF-β1 (1 or 10ng/mL) for 2hr, n = 4 replicates. The RNA was extracted and prepared for RT–PCR. The expression of cyclin D2, FKHR, SCC, 3βHSD and StAR were measured. TGFβRI and TGFβRII proteins were localised to postnatal rat ovary by immunohistochemistry. TGF-β1–3, TGFβRI and TGFβRII were present in rat ovaries as early as 4 days after birth. Expression of TGF-β1 mRNA increased 2-fold between day 4 and 12. TGF-β2 and TGF-β3 mRNAs declined between day 4 and 8 and remained low at day 12. The type I and II TGF-β receptors were differentially regulated with TGFβRI expression high at day 4, declining at day 8. In contrast, TGFβRII appeared to be ubiquitously expressed. Cyclin D2 mRNA expression was enhanced in the presence of both TGF-β1 and FSH, whereas FKHR mRNA expression declined. TGF-β1 had no impact on the steroidogenic mRNAs. TGFβRI and TGFβRII proteins were localised to the cytoplasm of oocytes, granulosa cells and theca cells. These studies indicate that TGF-β1 can exert effects on ovarian folliculogenesis as it is established during the postnatal period. Proliferation and apoptosis appear to be targets of TGF-β1 action. Supported by the NHMRC of Australia (Regkeys 241000, 198705, 441101 & 465415)

Effect of exogenous transforming growth factor β1 (TGF-β1) on early bovine embryo development

Zygote ◽  
2018 ◽  
Vol 26 (3) ◽  
pp. 232-241 ◽  
Author(s):  
Antonio D. Barrera ◽  
Elina V. García ◽  
Dora C. Miceli
Keyword(s):  
Growth Factor ◽  
Embryo Development ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Bovine Embryo ◽  
Cell Stage ◽  
Specific Expression ◽  
Early Action ◽  
Tgf Β1

SummaryDuring preimplantation development, embryos are exposed and have the capacity to respond to different growth factors present in the maternal environment. Among these factors, transforming growth factor β1 (TGF-β1) is a well known modulator of embryonic growth and development. However, its action during the first stages of development, when the embryo transits through the oviduct, has not been yet elucidated. The objective of the present study was to examine the effect of early exposure to exogenous TGF-β1 on embryo development and expression of pluripotency (OCT4, NANOG) and DNA methylation (DNMT1, DNMT3A, DNMT3B) genes in bovine embryos produced in vitro. First, gene expression analysis of TGF-β receptors confirmed a stage-specific expression pattern, showing greater mRNA abundance of TGFBR1 and TGFBR2 from the 2- to the 8-cell stage, before embryonic genome activation. Second, embryo culture for the first 48 h in serum-free CR1aa medium supplemented with 50 or 100 ng/ml recombinant TGF-β1 did not affect the cleavage and blastocyst rate (days 7 and 8). However, RT-qPCR analysis showed a significant increase in the relative abundance of NANOG and DNMT3A in the 8-cell stage embryos and expanded blastocysts (day 8) derived from TGF-β1 treated embryos. These results suggest an early action of exogenous TGF-β1 on the bovine embryo, highlighting the importance to provide a more comprehensive understanding of the role of TGF-β signalling during early embryogenesis.

scholarly journals Using sheep lines with mutations in single genes to better understand ovarian function

Reproduction ◽  
2013 ◽  
Vol 146 (4) ◽  
pp. R111-R123 ◽  
Author(s):  
Jennifer L Juengel ◽  
George H Davis ◽  
Kenneth P McNatty
Keyword(s):  
Growth Factor ◽  
Reproductive Success ◽  
Selection Pressure ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Transforming Growth Factor Β ◽  
Ovulation Rate ◽  
Regulatory Mechanisms ◽  
Biological Resource ◽  
Strong Selection

Livestock populations have been subjected to strong selection pressure to improve reproductive success, and this has led to the identification of lines of animals with increased fecundity. These animals provide a rich biological resource for discovery of genes and regulatory mechanisms that underpin improved reproductive success. To date, three genes, all related to the transforming growth factor β pathway, have been identified as having mutations that lead to alterations in ovulation in sheep. In addition, several other sheep lines have been identified with putative mutations in single genes with major effects on ovulation rate. This review is focused on the identification of the mutations affecting ovulation rate and how these discoveries have provided new insights into control of ovarian function.

Perianale Fisteln bei CED: vom Mausmodell zur Klinik

2018 ◽  
Vol 75 (5) ◽  
pp. 287-294
Author(s):  
Michael Scharl
Keyword(s):  
Growth Factor ◽  
Morbus Crohn ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 13

Zusammenfassung. Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft dar.

Learning more about the role of Latent transforming growth factor-β binding protein–1 (LTBP–1) – a knockout approach in mice

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
F Drews ◽  
S Knöbel ◽  
A Bosio ◽  
K Muhlack ◽  
M Moser ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β
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