KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells

Xin, Xiaoping; Li, Zhonghui; Zhong, Yuyi; Li, Qingqing; Wang, Jiaying; Zhang, Hao; Yuan, Xiaolong; Li, Jiaqi; Zhang, Zhe

doi:10.3390/ani9020054

Cited by 11 publications

(5 citation statements)

References 52 publications

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“…Kisspeptin at 50 and 100 nM concentrations increased the E 2 production by 1.6-1.8 fold (Table 2) and is consistent with the report in the porcine GCs (Xin et al, 2019). Further, upregulation of STAR and CYP19A1 gene transcripts by 100 nM Kp (Table 3) supports the stimulatory effect of 100 nM Kp on E 2 production.…”

Section: Discussionsupporting

confidence: 87%

Kisspeptin stimulates oestradiol biosynthesis by upregulating steroidogenic transcripts and proliferation markers in the bubaline granulosa cells in vitro

Sharma,

Patra,

Puttanarsappa

et al. 2024

Reprod Domestic Animals

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Kisspeptin (Kp), an upstream regulator of GnRH release, is essential for the development and function of reproductive axis. Previously, we demonstrated the localization of Kp and its receptor (Kiss1r) in the active follicle in the bubaline ovary. Present study aimed to determine the effect of Kp on granulosa cell (GCs) functions, especially oestradiol (E2) and progesterone (P4) production, and differential expression of genes regulating the proliferation, apoptosis and steroidogenesis in the buffalo. The ovaries with 6–10 mm size follicles obtained from the cyclic buffaloes after slaughtering were used for isolation of GCs for in vitro study. The primary GCs culture was treated with Kp (0, 10, 50 and 100 nM) and incubated for 48 h. Production of E2 and P4 was estimated in the culture supernatant by ELISA. The expression of gonadotropin receptors (FSHR and LHR), steroidogenic genes (STAR, 3β‐HSD, CYP19A1), proliferation marker (PCNA), apoptotic factors (CASP3 and BCL2) and Kp signalling molecule (extracellular signal‐regulated kinase 1/2, ERK1/2 and p‐ERK1/2) was studied in the GCs by qPCR. Significant E2 production was found in the Kp 50 and 100 nM groups (p < .05), whereas P4 production was reduced in Kp 100 nM group (p < .05). There was concomitant upregulation of FSHR, ERK1/2, STAR and CYP19A1 in the Kp 100 nM treated GCs. In addition, Kp at 100 nM stimulated the proliferation of GCs by upregulating the expression of BCL2 (5.0 fold) and PCNA (94.9 fold). Further, high immunoreactivity of p‐ERK1/2 was observed in the Kp‐treated GCs. It was concluded that Kp at 100 nM concentration stimulated E2 production by upregulating the steroidogenic pathway through ERK1/2, STAR and CYP19A1 and modulating PCNA and BCL2 expressions in the GCs. Further experiments are warranted using Kp antagonist in different combinations to establish the signalling pathway in Kp‐mediated steroidogenesis in the GCs for developing strategies to control ovarian functions.

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Section: Discussionsupporting

confidence: 87%

Kisspeptin stimulates oestradiol biosynthesis by upregulating steroidogenic transcripts and proliferation markers in the bubaline granulosa cells in vitro

Sharma,

Patra,

Puttanarsappa

et al. 2024

Reprod Domestic Animals

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“…Kisspeptin can regulate animal reproduction by regulating follicular development through the paracrine or autocrine pathway in the gonads. Kisspeptin treatment promotes progesterone secretion in cultured bovine granulosa cells [ 24 ], while transfection of the kiss1 gene into porcine ovarian granulosa cells promotes steroid secretion [ 25 ]. Our research group also showed that kisspeptin could promote the secretion of steroid hormones and cell proliferation in ovarian granulosa cells of Tan sheep in vitro (unpublished data), but the specific molecular mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of miRNA-mRNA in Ovarian Granulosa Cells Treated with Kisspeptin in Tan Sheep

Dai

Kang

Yang

et al. 2022

Animals

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Kisspeptin is a peptide hormone encoded by the kiss-1 gene that regulates animal reproduction. Our studies revealed that kisspeptin can regulate steroid hormone production and promote cell proliferation in ovarian granulosa cells of Tan sheep, but the mechanism has not yet been fully understood. We speculated that kisspeptin might promote steroid hormone production and cell proliferation by mediating the expression of specific miRNA and mRNA in granulosa cells. Accordingly, after granulosa cells were treated with kisspeptin, the RNA of cells was extracted to construct a cDNA library, and miRNA-mRNA sequencing was performed. Results showed that 1303 expressed genes and 605 expressed miRNAs were identified. Furthermore, eight differentially expressed miRNAs were found, and their target genes were significantly enriched in progesterone synthesis/metabolism, hormone biosynthesis, ovulation cycle, and steroid metabolism regulation. Meanwhile, mRNA was significantly enriched in steroid biosynthesis, IL-17 signaling pathway, and GnRH signaling pathway. Integrative analysis of miRNA-mRNA revealed that the significantly different oar-let-7b targets eight genes, of which EGR1 (early growth response-1) might play a significant role in regulating the function of granulosa cells, and miR-10a regulates lipid metabolism and steroid hormone synthesis by targeting HNRNPD. Additionally, PPI analysis revealed genes that are not miRNA targets but crucial to other biological processes in granulosa cells, implying that kisspeptin may also indirectly regulate granulosa cell function by these pathways. The findings of this work may help understand the molecular mechanism of kisspeptin regulating steroid hormone secretion, cell proliferation, and other physiological functions in ovarian granulosa cells of Tan sheep.

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“…A previous study has suggested that a high expression level of PIK3C is associated with follicular development and subfertility in mice [44]. A high mRNA level of PDK1 depresses cell apoptosis and affects cell entry in porcine GCs [45]. FOXO3 -specific-depletion in GCs decreases both cell proliferation and apoptosis of GCs and disrupts follicular growth in mice [46], and a lower mRNA expression of FOXO3 in GCs is involved in infertility in women [47].…”

Section: Discussionmentioning

confidence: 99%

P65 Targets FGFR1 to Regulate the Survival of Ovarian Granulosa Cells

Yuan

Kong

et al. 2019

Cells

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In female mammals, the abnormal apoptosis of ovarian granulosa cells (GCs) impairs follicular development and causes reproductive dysfunction. Many studies have indicated that the FGFR1 gene of the PI3K signaling pathway and the p65 subunit of the transcription factor NF-κB may regulate the proliferation and apoptosis of GCs involved in follicular development. However, little is known about whether p65 regulates the transcription of FGFR1, as well as the biological effects of p65 and FGFR1 on the survival of GCs and follicular development. In porcine follicles and GCs, we found that p65 and FGFR1 were exclusively expressed in the GCs of follicles, and the mRNA and protein levels of p65 and FGFR1 significantly increased from small to large follicles. Both p65 and FGFR1 were found to activate the PI3K signaling pathway, and the expressions of proliferation markers (PCNA and MKI67) and the anti-apoptotic gene BCL2 were significantly increased by p65 and FGFR1. Furthermore, both p65 and FGFR1 were observed to promote cell proliferation and inhibit the cell apoptosis of GCs, and p65 was confirmed to bind at the −348/−338 region of FGFR1 to positively regulate its transcription. Moreover, p65 was further found to enhance the pro-proliferation and anti-apoptotic effects of FGFR1. Taken together, p65 may target the −348/−338 region of FGFR1, promote the transcription of FGFR1, and enhance the pro-proliferation effect and anti-apoptotic effect of FGFR1 to facilitate the growth of follicles. This study will provide useful information for further investigations on the p65-mediated-FGFR1 signaling pathway during folliculogenesis in mammals.

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KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells

Cited by 11 publications

References 52 publications

Kisspeptin stimulates oestradiol biosynthesis by upregulating steroidogenic transcripts and proliferation markers in the bubaline granulosa cells in vitro

Kisspeptin stimulates oestradiol biosynthesis by upregulating steroidogenic transcripts and proliferation markers in the bubaline granulosa cells in vitro

Integrative Analysis of miRNA-mRNA in Ovarian Granulosa Cells Treated with Kisspeptin in Tan Sheep

P65 Targets FGFR1 to Regulate the Survival of Ovarian Granulosa Cells

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