KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods and Materials
2.1. Ethics Approval
2.2. Animals and Sample Preparation
2.3. Culture of Porcine GCs In Vitro
2.4. Real-Time Quantitative PCR Analysis
2.5. Cell Apoptosis Assay
2.6. Cell Cycle Analysis
2.7. ELISA for Measurements of Steroid Hormones
2.8. Data Analysis
3. Results
3.1. Expression of KISS1 during Follicular Maturation in Pigs
3.2. Biological Effects of KISS1 on Cell Apoptosis and Cell Cycle of GCs
3.3. Biological Effects of KISS1 on Synthesis of Estrogen in GCs
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Plant, T.M. Neuroendocrine control of the onset of puberty. Front. Neuroendocr. 2015, 38, 73–88. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, J.H.; Yoo, H.W. Control of puberty: Genetics, endocrinology, and environment. Curr. Opin. Endocrinol. Diabetes Obes. 2013, 20, 62–68. [Google Scholar] [CrossRef] [PubMed]
- Leka-Emiri, S.; Chrousos, G.P.; Kanaka-Gantenbein, C. The mystery of puberty initiation: Genetics and epigenetics of idiopathic central precocious puberty (ICPP). J. Endocrinol. Investig. 2017, 40, 789–802. [Google Scholar] [CrossRef] [PubMed]
- Adekunbi, D.A.; Li, X.F.; Li, S.; Adegoke, O.A.; Iranloye, B.O.; Morakinyo, A.O.; Lightman, S.L.; Taylor, P.D.; Poston, L.; O’Byrne, K.T. Role of amygdala kisspeptin in pubertal timing in female rats. PLoS ONE 2017, 12, e0183596. [Google Scholar] [CrossRef] [PubMed]
- Toro, C.A.; Aylwin, C.F.; Lomniczi, A. Hypothalamic Epigenetics Driving Female Puberty. J. Neuroendocr. 2018, 30. [Google Scholar] [CrossRef] [PubMed]
- Tanyapanyachon, P.; Amelkina, O.; Chatdarong, K. The expression of kisspeptin and its receptor in the domestic cat ovary and uterus in different stages of the ovarian cycle. Theriogenology 2018, 117, 40–48. [Google Scholar] [CrossRef] [PubMed]
- Hu, K.L.; Zhao, H.; Chang, H.M.; Yu, Y.; Qiao, J. Kisspeptin/Kisspeptin Receptor System in the Ovary. Front. Endocrinol. (Lausanne) 2017, 8, 365. [Google Scholar] [CrossRef]
- Colledge, W.H. Transgenic mouse models to study Gpr54/kisspeptin physiology. Peptides 2009, 30, 34–41. [Google Scholar] [CrossRef]
- Lapatto, R.; Pallais, J.C.; Zhang, D.S.; Chan, Y.M.; Mahan, A.; Cerrato, F.; Le, W.W.; Hoffman, G.E.; Seminara, S.B. Kiss1(−/−) mice exhibit more variable hypogonadism than Gpr54(−/−) mice. Endocrinology 2007, 148, 4927–4936. [Google Scholar] [CrossRef]
- Funes, S.; Hedrick, J.A.; Vassileva, G.; Markowitz, L.; Abbondanzo, S.; Golovko, A.; Yang, S.J.; Monsma, F.J.; Gustafson, E.L. The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem. Biopyhs. Res. Commun. 2003, 312, 1357–1363. [Google Scholar] [CrossRef]
- Seminara, S.B.; Messager, S.; Chatzidaki, E.E.; Thresher, R.R.; Acierno, J.S.; Shagoury, J.K.; Bo-Abbas, Y.; Kuohung, W.; Schwinof, K.M.; Hendrick, A.G.; et al. The GPR54 gene as a regulator of puberty. N. Engl. J. Med. 2003, 349, 1614–1627. [Google Scholar] [CrossRef] [PubMed]
- Chakravarthi, V.P.; Khristi, V.; Ghosh, S.; Yerrathota, S.; Dai, E.; Roby, K.F.; Wolfe, M.W.; Rumi, M.A.K. ESR2 Is Essential for Gonadotropin-Induced Kiss1 Expression in Granulosa Cells. Endocrinology 2018, 159, 3860–3873. [Google Scholar] [CrossRef] [PubMed]
- Ricu, M.A.; Ramirez, V.D.; Paredes, A.H.; Lara, H.E. Evidence for a celiac ganglion-ovarian kisspeptin neural network in the rat: Intraovarian anti-kisspeptin delays vaginal opening and alters estrous cyclicity. Endocrinology 2012, 153, 4966–4977. [Google Scholar] [CrossRef] [PubMed]
- Saatcioglu, H.D.; Cuevas, I.; Castrillon, D.H. Control of Oocyte Reawakening by Kit. PLoS Genet. 2016, 12, e1006215. [Google Scholar] [CrossRef] [PubMed]
- Douville, G.; Sirard, M.A. Changes in granulosa cells gene expression associated with growth, plateau and atretic phases in medium bovine follicles. J. Ovarian Res. 2014, 7, 50. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khan, M.I.; Dias, F.C.; Dufort, I.; Misra, V.; Sirard, M.A.; Singh, J. Stable reference genes in granulosa cells of bovine dominant follicles during follicular growth, FSH stimulation and maternal aging. Reprod. Fertil. Dev. 2016, 28, 795–805. [Google Scholar] [CrossRef] [PubMed]
- Matsuda, F.; Inoue, N.; Manabe, N.; Ohkura, S. Follicular growth and atresia in mammalian ovaries: Regulation by survival and death of granulosa cells. J. Reprod. Dev. 2012, 58, 44–50. [Google Scholar] [CrossRef]
- Valdez, K.E.; Turzillo, A.M. Regulation of nuclear factor-kappaB (NF-kappaB) activity and apoptosis by estradiol in bovine granulosa cells. Mol. Cell Endocrinol. 2005, 243, 66–73. [Google Scholar] [CrossRef]
- Chou, C.H.; Chen, M.J. The Effect of Steroid Hormones on Ovarian Follicle Development. Vitam. Horm. 2018, 107, 155–175. [Google Scholar]
- McGee, E.A.; Hsueh, A.J. Initial and cyclic recruitment of ovarian follicles. Endocr. Rev. 2000, 21, 200–214. [Google Scholar] [CrossRef]
- Zheng, W.; Nagaraju, G.; Liu, Z.; Liu, K. Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary. Mol. Cell Endocrinol. 2012, 356, 24–30. [Google Scholar] [CrossRef] [PubMed]
- Makker, A.; Goel, M.M.; Mahdi, A.A. PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: An update. J. Mol. Endocrinol. 2014, 53, R103–R118. [Google Scholar] [CrossRef] [PubMed]
- Hu, C.L.; Cowan, R.G.; Harman, R.M.; Quirk, S.M. Cell cycle progression and activation of Akt kinase are required for insulin-like growth factor I-mediated suppression of apoptosis in granulosa cells. Mol. Endocrinol. 2004, 18, 326–338. [Google Scholar] [CrossRef] [PubMed]
- Hu, K.L.; Zhao, H.; Min, Z.; He, Y.; Li, T.; Zhen, X.; Ren, Y.; Chang, H.M.; Yu, Y.; Li, R. Increased Expression of KISS1 and KISS1 Receptor in Human Granulosa Lutein Cells-Potential Pathogenesis of Polycystic Ovary Syndrome. Reprod. Sci. 2018. [Google Scholar] [CrossRef] [PubMed]
- Blasco, V.; Pinto, F.M.; Fernandez-Atucha, A.; Prados, N.; Tena-Sempere, M.; Fernandez-Sanchez, M.; Candenas, L. Altered expression of the kisspeptin/KISS1R and neurokinin B/NK3R systems in mural granulosa and cumulus cells of patients with polycystic ovarian syndrome. J. Assist. Reprod. Genet. 2019, 36, 113–120. [Google Scholar] [CrossRef] [PubMed]
- Basini, G.; Grasselli, F.; Bussolati, S.; Ciccimarra, R.; Maranesi, M.; Bufalari, A.; Parillo, F.; Zerani, M. Presence and function of kisspeptin/KISS1R system in swine ovarian follicles. Theriogenology 2018, 115, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Patterson, J.L.; Willis, H.J.; Kirkwood, R.N.; Foxcroft, G.R. Impact of boar exposure on puberty attainment and breeding outcomes in gilts. Theriogenology 2002, 57, 2015–2025. [Google Scholar] [CrossRef]
- Ieda, N.; Uenoyama, Y.; Tajima, Y.; Nakata, T.; Kano, M.; Naniwa, Y.; Watanabe, Y.; Minabe, S.; Tomikawa, J.; Inoue, N.; et al. KISS1 gene expression in the developing brain of female pigs in pre- and peripubertal periods. J. Reprod. Dev. 2014, 60, 312–316. [Google Scholar] [CrossRef]
- Zhuo, Y.; Zhou, D.; Che, L.; Fang, Z.; Lin, Y.; Wu, D. Feeding prepubescent gilts a high-fat diet induces molecular changes in the hypothalamus-pituitary-gonadal axis and predicts early timing of puberty. Nutrition 2014, 30, 890–896. [Google Scholar] [CrossRef]
- Liu, J.Y.; Du, X.; Zhou, J.L.; Pan, Z.X.; Liu, H.L.; Li, Q.F. MicroRNA-26b Functions as a Proapoptotic Factor in Porcine Follicular Granulosa Cells by Targeting Sma-and Mad-Related Protein 4. Biol. Reprod. 2014, 91, 1–12. [Google Scholar] [CrossRef]
- Yuan, X.; Deng, X.; Zhou, X.; Zhang, A.; Xing, Y.; Zhang, Z.; Zhang, H.; Li, J. MiR-126-3p promotes the cell proliferation and inhibits the cell apoptosis by targeting TSC1 in the porcine granulosa cells. In Vitro Cell. Dev. Biol. Anim. 2018, 54, 715–724. [Google Scholar] [CrossRef] [PubMed]
- Yuan, X.; Zhou, X.; He, Y.; Zhong, Y.; Zhang, A.; Zhang, Z.; Zhang, H.; Li, J. C/EBPbeta Promotes STAT3 Expression and Affects Cell Apoptosis and Proliferation in Porcine Ovarian Granulosa Cells. Genes 2018, 9, 295. [Google Scholar] [CrossRef] [PubMed]
- Fernandois, D.; Cruz, G.; Na, E.K.; Lara, H.E.; Paredes, A.H. Kisspeptin level in the aging ovary is regulated by the sympathetic nervous system. J. Endocrinol. 2017, 232, 97–105. [Google Scholar] [CrossRef] [PubMed]
- Naniwa, Y.; Nakatsukasa, K.; Setsuda, S.; Oishi, S.; Fujii, N.; Matsuda, F.; Uenoyama, Y.; Tsukamura, H.; Maeda, K.; Ohkura, S. Effects of full-length kisspeptin administration on follicular development in Japanese Black beef cows. J. Reprod. Dev. 2013, 59, 588–594. [Google Scholar] [CrossRef] [PubMed]
- Bhattacharya, M.; Babwah, A.V. Kisspeptin: Beyond the brain. Endocrinology 2015, 156, 1218–1227. [Google Scholar] [CrossRef] [PubMed]
- Castellano, J.M.; Gaytan, M.; Roa, J.; Vigo, E.; Navarro, V.M.; Bellido, C.; Dieguez, C.; Aguilar, E.; Sanchez-Criado, J.E.; Pellicer, A.; et al. Expression of KiSS-1 in rat ovary: Putative local regulator of ovulation? Endocrinology 2006, 147, 4852–4862. [Google Scholar] [CrossRef] [PubMed]
- Khristi, V.; Chakravarthi, V.P.; Singh, P.; Ghosh, S.; Pramanik, A.; Ratri, A.; Borosha, S.; Roby, K.F.; Wolfe, M.W.; Rumi, M.A.K. ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation. Mol. Cell. Endocrinol. 2018. [Google Scholar] [CrossRef]
- Gorkem, U.; Togrul, C.; Arslan, E.; Oruc, A.S.; Duman, N.B. Is there a role for kisspeptin in pathogenesis of polycystic ovary syndrome? Gynecol. Endocrinol. 2018, 34, 157–160. [Google Scholar] [CrossRef]
- Emekci Ozay, O.; Ozay, A.C.; Acar, B.; Cagliyan, E.; Secil, M.; Kume, T. Role of kisspeptin in polycystic ovary syndrome (PCOS). Gynecol. Endocrinol. 2016, 32, 718–722. [Google Scholar] [CrossRef]
- Li, Q.; He, H.; Zhang, Y.L.; Li, X.M.; Guo, X.; Huo, R.; Bi, Y.; Li, J.; Fan, H.Y.; Sha, J. Phosphoinositide 3-kinase p110delta mediates estrogen- and FSH-stimulated ovarian follicle growth. Mol. Endocrinol. 2013, 27, 1468–1482. [Google Scholar] [CrossRef]
- Hunter, M.G. Oocyte maturation and ovum quality in pigs. Rev. Reprod. 2000, 5, 122–130. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, L.; Huang, J.; Yang, N.; Greshock, J.; Liang, S.; Hasegawa, K.; Giannakakis, A.; Poulos, N.; O’Brien-Jenkins, A.; Katsaros, D.; et al. Integrative genomic analysis of phosphatidylinositol 3′-kinase family identifies PIK3R3 as a potential therapeutic target in epithelial ovarian cancer. Clin. Cancer Res. 2007, 13, 5314–5321. [Google Scholar] [CrossRef] [PubMed]
- Yan, H.; Zhang, J.; Wen, J.; Wang, Y.; Niu, W.; Teng, Z.; Zhao, T.; Dai, Y.; Zhang, Y.; Wang, C.; et al. CDC42 controls the activation of primordial follicles by regulating PI3K signaling in mouse oocytes. BMC Biol. 2018, 16, 73. [Google Scholar] [CrossRef] [PubMed]
- Reddy, P.; Adhikari, D.; Zheng, W.; Liang, S.; Hamalainen, T.; Tohonen, V.; Ogawa, W.; Noda, T.; Volarevic, S.; Huhtaniemi, I.; et al. PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Hum. Mol. Genet. 2009, 18, 2813–2824. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Z.; Castrillon, D.H.; Zhou, W.; Richards, J.S. FOXO1/3 depletion in granulosa cells alters follicle growth, death and regulation of pituitary FSH. Mol. Endocrinol. 2013, 27, 238–252. [Google Scholar] [CrossRef] [PubMed]
- Yamamoto, H.; Yamashita, Y.; Saito, N.; Hayashi, A.; Hayashi, M.; Terai, Y.; Ohmichi, M. Lower FOXO3 mRNA expression in granulosa cells is involved in unexplained infertility. J. Obstet. Gynaecol. Res. 2017, 43, 1021–1028. [Google Scholar] [CrossRef] [PubMed]
- Cao, X.H.; Wang, X.Y.; Lu, L.L.; Li, X.Y.; Di, R.; He, X.Y.; Hu, W.P.; Zeng, X.Y.; Liu, Q.Y.; Chu, M.X. Expression and Functional Analysis of the BCL2-Associated Agonist of Cell Death (BAD) Gene in the Sheep Ovary During the Reproductive Cycle. Front. Endocrinol. 2018, 9. [Google Scholar] [CrossRef]
- Adhikari, D.; Flohr, G.; Gorre, N.; Shen, Y.; Yang, H.R.; Lundin, E.; Lan, Z.J.; Gambello, M.J.; Liu, K. Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles. Mol. Hum. Reprod. 2009, 15, 765–770. [Google Scholar] [CrossRef]
- Schams, D.; Berisha, B. Steroids as local regulators of ovarian activity in domestic animals. Domest. Anim. Endocrin. 2002, 23, 53–65. [Google Scholar] [CrossRef]
- Conley, A.J.; Howard, H.J.; Slanger, W.D.; Ford, J.J. Steroidogenesis in the preovulatory porcine follicle. Biol. Reprod. 1994, 51, 655–661. [Google Scholar] [CrossRef] [Green Version]
Name | Sequence | Product (bp) | Accession Number |
---|---|---|---|
CDS-KISS1 | F: GAATTCATGAATGCACTGGTTTTTTGG | 431 | NM_001134964.1 |
R: CGCCGGCGAGTCAGAGCGGGCCGCGGAA | |||
qRT-PCR-KISS1 | F: AACCAGCATCTTCTCACCAGG | 192 | NM_001134964.1 |
R: CTTTCTCTCCGCACAACGC | |||
qRT-PCR-GAPDH | F: TCCCGCCAACATCAAAT | 163 | XM_021091114.1 |
R: CACGCCCATCACAAACAT | |||
qRT-PCR-PIK3CG | F: AACGGGCTTTGAGATAGTGAA | 184 | NM_213939.1 |
R: AAGTTGCTTGGTTGGTGGATA | |||
qRT-PCR-PIK3C1 | F: CAAGTGAGAATGGTCCGAATG | 152 | NM_006218.3 |
R: GTGGAAGAGTTTGCCTGTTTT | |||
qRT-PCR-PDK1 | F: AAATCACCAGGACAGCCAATA | 190 | NM_001159608.1 |
R: CTTCTCGGTCACTCATCTTCAC | |||
qRT-PCR-FOXO3 | F: ACAAACGGCTCACTCTGTCCCA | 85 | NM_001135959.1 |
R: GAACTGTTGCTGTCGCCCTTATC | |||
qRT-PCR-TSC2 | F: CGAGGTGGTGTCCTACGAGAT | 115 | XM_005655162.3 |
R: GAGCAGGCGTTCAATGATGTT | |||
qRT-PCR-BAD | F: AGTCGCCACTGCTCTTACCC | 172 | XM_021082883.1 |
R: TCTTGAAGGAACCCTGGAAATC | |||
qRT-PCR-Star | F: GGAAAAGACACAGTCATCACCCAT | 121 | NM_213755.2 |
R: CAGCAAGCACACACACGGAAC | |||
qRT-PCR-CYP17 | F: AAGCCAAGACGAACGCAGAAAG | 228 | NM_214428.1 |
R: TAGATGGGGCACGATTGAAACC | |||
qRT-PCR-3B-HSD | F: GGGGCTTCTGTCTTGATTCCA | 284 | NM_001004049.2 |
R: GGTTTTCAGTGCTTCCTTGTGC | |||
qRT-PCR-17B-HSD | F: CCCAACGCAGGAGACTCAAAAT | 149 | NM_214306.1 |
R: CCAGAGCCCATAACGAAGACAGA | |||
qRT-PCR-CYP19A | F: GCTGGACACCTCTAACAACCTCTT | 91 | NM_214430.1 |
R: TTGCCATTCATCAAAATAACCCT | |||
qRT-PCR-ESR1 | F: GATGCCTTGGTCTGGGTGAT | 124 | XM_003468423.2 |
R: AGTGTTCCGTGCCCTTGTTA | |||
qRT-PCR-ESR2 | F: AAGGGAAAAGGAGGATGGGACA | 202 | NM_0010011533.1 |
R: CAGATAGGGACTGCGTGGAGGT |
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Share and Cite
Xin, X.; Li, Z.; Zhong, Y.; Li, Q.; Wang, J.; Zhang, H.; Yuan, X.; Li, J.; Zhang, Z. KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells. Animals 2019, 9, 54. https://doi.org/10.3390/ani9020054
Xin X, Li Z, Zhong Y, Li Q, Wang J, Zhang H, Yuan X, Li J, Zhang Z. KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells. Animals. 2019; 9(2):54. https://doi.org/10.3390/ani9020054
Chicago/Turabian StyleXin, Xiaoping, Zhonghui Li, Yuyi Zhong, Qingqing Li, Jiaying Wang, Hao Zhang, Xiaolong Yuan, Jiaqi Li, and Zhe Zhang. 2019. "KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells" Animals 9, no. 2: 54. https://doi.org/10.3390/ani9020054