Knockdown of CYP19A1 in Buffalo Follicular Granulosa Cells Results in Increased Progesterone Secretion and Promotes Cell Proliferation

Lu, Xingrong; Duan, Anqin; Ma, Xiaoya; Liang, Shasha; Deng, Tingxian

doi:10.3389/fvets.2020.539496

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…This phenomenon was attributed to a reduction in cell proliferation at higher genistein concentrations. The most plausible explanation for the reduced 17βestradiol content in the spent medium of cultured GCs was the reduced expression of CYP19A1, which was reported in bovine [42] and porcine [18] ovarian cells and in our present result. These findings were corroborated by the results of the previous report [43] in which genistein exerted a biphasic response on estrogen receptors by structurally mimicking 17β-estradiol.…”

Section: Growth-related Genesupporting

confidence: 74%

Genistein effect in cultured ovine ovarian granulosa cells

Singh,

Kumar,

Nandi

et al. 2024

J Biochem & Molecular Tox

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Genistein, an isoflavone has the potential to mimic, augment, or dysregulate the steroid hormone production pathways. We hypothesized that genistein affects the granulosa cell (GCs) functions through a series of biochemical, molecular, and genomic cascades. The present study was conducted to evaluate the impact of genistein exposure on GCs viability, apoptosis, and steroidogenesis. The present study involved 3/5 days of exposure to genistein on GCs collected from abattoir‐derived ovine ovaries at doses of 0, 1, 10, 25, 50, and 100 µM. The harvested GCs were used for growth, cytotoxicity, and gene expression studies related to apoptosis, growth, and steroidogenesis. We observed that genistein had both stimulatory at 10 and 25 µM levels as well as inhibitory effects at 50 and 100 µM levels on the growth and proliferation of GCs. Genistein significantly decreased the levels of 17β‐estradiol at higher exposure (50 and 100 µM), whereas the progesterone level increased significantly as the genistein exposure increased. Additionally, genistein could also alter the mRNA expression of the steroidogenic receptor, enzymes, proteins, and growth‐related genes suggesting that genistein could potentially alter the steroidogenic pathways. We conclude that genistein can interfere with cell survival and steroidogenesis by exhibiting a dose‐dependent biphasic response on the viability, growth‐related parameters, and the synthesis of 17β‐estradiol in the cultured GCs.

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Section: Growth-related Genesupporting

confidence: 74%

Genistein effect in cultured ovine ovarian granulosa cells

Singh,

Kumar,

Nandi

et al. 2024

J Biochem & Molecular Tox

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“…Conversion of androgen to estrogen is catalyzed by Cyp19a1, which is a critical enzyme in estrogen synthesis. Circulating estrogen levels are regulated by the pituitary FSH, which modulates the transcription of Cyp19a1 in the ovarian follicular granulosa cells 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

“…The non-canonical pathways are involved in cell polarity and the regulation of intracellular calcium levels. Wnt/β-catenin signaling pathway has been recognized to contribute to ovarian regulation of steroidogenesis, as β-catenin is an essential transcriptional modulator of Cyp19a1 8 .…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Wnt10a causes female infertility via the β-catenin/Cyp19a1 pathway in mice

Zhang¹,

Tasaki²,

Tsukamoto³

et al. 2022

Int. J. Med. Sci.

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Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. The expression of β-catenin signaling was significantly lower in the ovaries of the Wnt10a KO mice compared with wild-type (WT) mice. In addition, the estrous cycles were disrupted, ovarian follicles were diminished, and endometria were thinner, accompanied by lower serum estrogen levels, and higher testosterone and progesterone levels in Wnt10a KO mice. The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through β-catenin and Cyp19a1signaling pathways in mice.

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“…Cyp19a1 expression is regulated by FSH and LH at the mRNA level. CYP19A1 knockdown modulates hormone secretion and cell proliferation in follicular granulosa cells (40). ERα KO mice exhibit chronically elevated LH, E2, and testosterone due to disrupted negative feedback, with Cyp19a1 signi cantly decreased in ERα-deleted granulosa cells.…”

Section: Discussionmentioning

confidence: 99%

Single-cell sequencing reveals transcriptional dynamics regulated by ERα in mouse ovaries

Hu,

Gui,

Cao

et al. 2023

Preprint

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Estrogen receptor α (ERα) is a crucial regulator of reproductive function, mediating the diverse effects of estrogen on the development and function of the ovary. However, the molecular mechanisms underlying ERα-regulated transcriptional dynamics in ovarian cells remain poorly understood. In the present study, we generated ERα knockout (αERKO) mice through CRISPR/Cas9 strategy. Then we employed single-cell RNA sequencing technology (scRNA-seq) to profile the transcriptomes of individual cells in wild type (WT) and αERKO mouse ovaries to uncover novel insights into ERα-regulated transcriptional change and ovarian cellular heterogeneity. Using several bioinformatics analyses, our study identified distinct cell populations within the ovarian tissue, including 5 distinct cell clusters associated with oocytes and 7 with granulosa cells. We further conducted differential gene expression analysis to explore the transcriptional profiles of these cell populations in response to ERα deletion. Our findings revealed that ERα deletion led to the dysregulation of genes involved in ovarian infertility, ovulation cycle, and steroidogenesis in oocytes and granulosa cells, indicating that ERα plays a central role in modulating the transcriptional landscape of ovarian cells. Consequently, we confirmed that Greb1, a prototypical ERα target gene, was induced by ERα binding to ERE upstream of the Greb1 promoter in granulosa cells. Additionally, we uncovered a complex network of signaling pathways that were significantly modulated by ERα, implicating their involvement in the regulation of ovarian function and ovulation process. In conclusion, our study offers an in-depth, single-cell resolution of ERα-regulated transcriptional dynamics in mouse ovaries, enhancing our understanding of ERα's role in female reproductive biology and providing potential targets for novel therapeutic interventions for ovarian disorders.

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Knockdown of CYP19A1 in Buffalo Follicular Granulosa Cells Results in Increased Progesterone Secretion and Promotes Cell Proliferation

Cited by 6 publications

References 27 publications

Genistein effect in cultured ovine ovarian granulosa cells

Genistein effect in cultured ovine ovarian granulosa cells

Deficiency of Wnt10a causes female infertility via the β-catenin/Cyp19a1 pathway in mice

Single-cell sequencing reveals transcriptional dynamics regulated by ERα in mouse ovaries

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