Non-canonical cyclic AMP SMAD1/5/8 signalling in human granulosa cells

Bertoldo, Michael J.; Cheung, Man Yee; SIa, Zhanaeva; Agapiou, David; Corley, Susan M.; Wilkins, Marc R.; Richani, Dulama; Harrison, Craig A.; Gilchrist, Robert B.

doi:10.1016/j.mce.2019.04.003

Cited by 11 publications

(7 citation statements)

References 56 publications

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“…AMH was shown to be present at high levels in puberty once this period presented high rates of oocyte maturation and at low levels in menopause [ 178 ]. Other pathways have been reported to control the regulation of follicular and oocyte development, e.g., the BMP-SMAD1/5/8 pathway is essential in follicular activation and development, GCs proliferation, atresia, and luteinization, and the Notch pathway is activated by gonadotrophins, which is important in oocyte development [ 179 , 180 , 181 ].…”

Section: Influence Of Fsh On Germ Cellsmentioning

confidence: 99%

Actions and Roles of FSH in Germinative Cells

Recchia

Jorge

Pessôa

et al. 2021

IJMS

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Follicle stimulating hormone (FSH) is produced by the pituitary gland in a coordinated hypothalamic–pituitary–gonadal (HPG) axis event, plays important roles in reproduction and germ cell development during different phases of reproductive development (fetal, neonatal, puberty, and adult life), and is consequently essential for fertility. FSH is a heterodimeric glycoprotein hormone of two dissociable subunits, α and β. The FSH β-subunit (FSHβ) function starts upon coupling to its specific receptor: follicle-stimulating hormone receptor (FSHR). FSHRs are localized mainly on the surface of target cells on the testis and ovary (granulosa and Sertoli cells) and have recently been found in testicular stem cells and extra-gonadal tissue. Several reproduction disorders are associated with absent or low FSH secretion, with mutation of the FSH β-subunit or the FSH receptor, and/or its signaling pathways. However, the influence of FSH on germ cells is still poorly understood; some studies have suggested that this hormone also plays a determinant role in the self-renewal of germinative cells and acts to increase undifferentiated spermatogonia proliferation. In addition, in vitro, together with other factors, it assists the process of differentiation of primordial germ cells (PGCLCs) into gametes (oocyte-like and SSCLCs). In this review, we describe relevant research on the influence of FSH on spermatogenesis and folliculogenesis, mainly in the germ cell of humans and other species. The possible roles of FSH in germ cell generation in vitro are also presented.

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Section: Influence Of Fsh On Germ Cellsmentioning

confidence: 99%

Actions and Roles of FSH in Germinative Cells

Recchia

Jorge

Pessôa

et al. 2021

IJMS

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“…Expression of FSH receptor on the granulosa cell surface marks the beginning of folliculogenesis [ 14 ]. Genes activated through the cAMP pathway further increase proliferation of GCs and support this process [ 28 ]. An overview of these molecular mechanisms is presented in Figure 1 .…”

Section: The Main Metabolic and Signaling Pathways Involved In Phymentioning

confidence: 99%

“…Both GDF9 and BMP15 bind to type II BMP protein receptors in granulosa cells and thus initiate intracellular SMAD signaling. This BMP-SMAD1/5/8 pathway is important in follicular activation and development, GC cell proliferation, atresia and luteinization [ 28 ]. A summary of these processes is presented in Figure 2 .…”

Section: The Main Metabolic and Signaling Pathways Involved In Phymentioning

confidence: 99%

“…In turn, neighboring GCs aromatize these androgens to estrogens. In this way, hormone production is greatly It has been hypothesized that the BMP-SMAD1/5/8 pathway is functionally linked to the gonadotropin/cAMP pathway in developing GCs [28]. FSH was shown to upregulate the expression of various BMP receptors, as well as enhance SMAD signaling in the granulosa-like KGN tumor cell line [33].…”

Section: The Main Metabolic and Signaling Pathways Involved In Physiological Processes Of Granulosa Cellsmentioning

confidence: 99%

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The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs—A Review Based on Cellular and Molecular Knowledge

Józkowiak

Hutchings

Jankowski

et al. 2020

Cells

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Ovarian Granulosa Cells (GCs) are known to proliferate in the developing follicle and undergo several biochemical processes during folliculogenesis. They represent a multipotent cell population that has been differentiated to neuronal cells, chondrocytes, and osteoblasts in vitro. However, progression and maturation of GCs are accompanied by a reduction in their stemness. In the developing follicle, GCs communicate with the oocyte bidirectionally via gap junctions. Together with neighboring theca cells, they play a crucial role in steroidogenesis, particularly the production of estradiol, as well as progesterone following luteinization. Many signaling pathways are known to be important throughout the follicle development, leading either towards luteinization and release of the oocyte, or follicular atresia and apoptosis. These signaling pathways include cAMP, PI3K, SMAD, Hedgehog (HH), Hippo and Notch, which act together in a complex manner to control the maturation of GCs through regulation of key genes, from the primordial follicle to the luteal phase. Small molecules such as resveratrol, a phytoalexin found in grapes, peanuts and other dietary constituents, may be able to activate/inhibit these signaling pathways and thereby control physiological properties of GCs. This article reviews the current knowledge about granulosa stem cells, the signaling pathways driving their development and maturation, as well as biological activities of resveratrol and its properties as a pro-differentiation agent.

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“…During growth and development of the oocyte, the oocyte is closely related to the surrounding granulosa cells (18). The nutrients during the growth and development of the oocyte are provided by the surrounding granulosa cells, and the granulosa cells provide growth regulators to promote oocyte maturation (19). The ovaries of PCOS patients contain twice as many follicles at various stages of development.…”

Section: Discussionmentioning

confidence: 99%

lncRNA H19 acts as a ceRNA to regulate the expression of CTGF by targeting miR-19b in polycystic ovary syndrome

Sun

Yan

Liu

et al. 2020

Braz J Med Biol Res

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The etiology of polycystic ovary syndrome (PCOS) is complex and the pathogenesis is not fully understood. Some studies have shown that dysregulation of ovarian granulosa cells may be related to abnormal follicles and excessive androgen in women with PCOS. Our team has also confirmed the high expression status of H19 in PCOS patients in the early stage. However, the relationship between H19 and miR-19b in the development of PCOS is still unknown. Therefore, we used bioinformatics to predict the binding sites of human H19 and miR-19b, and of miR-19b and CTGF genes. After the silencing and overexpression of H19, real-time polymerase chain reaction (PCR) was used to detect the expressions of H19, miR-19b, and CTGF. Western blotting was used to detect CTGF protein. Proliferation of KGN cells after H19 silencing was detected by CCK8. Flow cytometry was used to detect the apoptosis of KGN cells after H19 silencing. After the overexpression of H19, it was found that the expression of miR-19b gene decreased and the expression of CTGF increased, whereas silencing of H19 did the opposite. In addition, H19 could promote cell proliferation and decrease cell apoptosis. Finally, luciferase reporter assays showed that the 3 0-end sequences of lncRNA H19 and CTGF contained the binding site of miR-19b. In conclusion, our study indicated that lncRNA H19 acted as a ceRNA to bind to miR-19b via a ''sponge'' to regulate the effect of CTGF on KGN cells, which may play a vital role in PCOS.

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Non-canonical cyclic AMP SMAD1/5/8 signalling in human granulosa cells

Cited by 11 publications

References 56 publications

Actions and Roles of FSH in Germinative Cells

Actions and Roles of FSH in Germinative Cells

The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs—A Review Based on Cellular and Molecular Knowledge

lncRNA H19 acts as a ceRNA to regulate the expression of CTGF by targeting miR-19b in polycystic ovary syndrome

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