Low Expression of SEMA6C Accelerates the Primordial Follicle Activation in the Neonatal Mouse Ovary

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2017 Sep 8

PMID 28881413

Citations 10

Authors

Su Zhou

Wei Yan

Wei Shen

Jing Cheng

Yueyue Xi

Suzhen Yuan

Fangfang Fu

Ting Ding

Aiyue Luo

Shixuan Wang

Affiliations

Soon will be listed here.

Abstract

The primordial follicle assembly, activation and the subsequent development are critical processes for female reproduction. A limited number of primordial follicles are activated to enter the growing follicle pool each wave, and the primordial follicle pool progressively diminishes over a woman's life-time. The number of remaining primordial follicles represents the ovarian reserve. Identification and functional investigation of the factors involved in follicular initial recruitment will be of great significance to the understanding of the female reproduction process and ovarian ageing. In this study, we aimed to study whether and how semaphorin 6C (Sema6c) regulated the primordial follicle activation in the neonatal mouse ovary. The attenuation of SEMA6C expression by SiRNA accelerated the primordial follicle activation in the in vitro ovary culture system. PI3K-AKT-rpS6 pathway was activated when SEMA6C expression was down-regulated. And the LY294002 could reverse the effect of low SEMA6C expression on primordial follicle activation. Our findings revealed that Sema6c was involved in the activation of primordial follicles, and the down-regulation of SEMA6C led to massive primordial follicle activation by interacting with the PI3K-AKT-rpS6 pathway, which might also provide valuable information for understanding premature ovarian failure and ovarian ageing.

Citing Articles

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions.

Ju W, Zhao Y, Yu Y, Zhao S, Xiang S, Lian F Front Endocrinol (Lausanne). 2024; 15:1361289.

PMID: 38694941 PMC: 11061492. DOI: 10.3389/fendo.2024.1361289.

Semaphorin 6 Family-An Important Yet Overlooked Group of Signaling Proteins Involved in Cancerogenesis.

Wagner W, Ochman B, Wagner W Cancers (Basel). 2023; 15(23).

PMID: 38067240 PMC: 10705753. DOI: 10.3390/cancers15235536.

SEMA6C: a novel adhesion-independent FAK and YAP activator, required for cancer cell viability and growth.

Fard D, Testa E, Panzeri V, Rizzolio S, Bianchetti G, Napolitano V Cell Mol Life Sci. 2023; 80(4):111.

PMID: 37002363 PMC: 10066115. DOI: 10.1007/s00018-023-04756-1.

Integrated Analysis of mRNAs and Long Non-Coding RNAs Expression of Oviduct That Provides Novel Insights into the Prolificacy Mechanism of Goat ().

Sun Z, Zhang Z, Liu Y, Ren C, He X, Jiang Y Genes (Basel). 2022; 13(6).

PMID: 35741792 PMC: 9222479. DOI: 10.3390/genes13061031.

Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells.

Tang X, Dong H, Fang Z, Li J, Yang Q, Yao T Reprod Biol Endocrinol. 2022; 20(1):84.

PMID: 35610622 PMC: 9128268. DOI: 10.1186/s12958-022-00956-9.

References

Zhang H, Liu K . Cellular and molecular regulation of the activation of mammalian primordial follicles: somatic cells initiate follicle activation in adulthood. Hum Reprod Update. 2015; 21(6):779-86. DOI: 10.1093/humupd/dmv037. View

Castrillon D, Miao L, Kollipara R, Horner J, DePinho R . Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science. 2003; 301(5630):215-8. DOI: 10.1126/science.1086336. View

Giacobini P, Prevot V . Semaphorins in the development, homeostasis and disease of hormone systems. Semin Cell Dev Biol. 2012; 24(3):190-8. DOI: 10.1016/j.semcdb.2012.11.005. View

Hsueh A, Kawamura K, Cheng Y, Fauser B . Intraovarian control of early folliculogenesis. Endocr Rev. 2014; 36(1):1-24. PMC: 4309737. DOI: 10.1210/er.2014-1020. View

Ren Y, Suzuki H, Jagarlamudi K, Golnoski K, McGuire M, Lopes R . Lhx8 regulates primordial follicle activation and postnatal folliculogenesis. BMC Biol. 2015; 13:39. PMC: 4487509. DOI: 10.1186/s12915-015-0151-3. View

Adhikari D, Flohr G, Gorre N, Shen Y, Yang H, Lundin E . Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles. Mol Hum Reprod. 2009; 15(12):765-70. DOI: 10.1093/molehr/gap092. View

Kim S, Ebbert K, Cordeiro M, Romero M, Zhu J, Serna V . Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal ovarian function through promoting survival and overgrowth of ovarian follicles. Endocrinology. 2015; 156(4):1464-76. PMC: 4399322. DOI: 10.1210/en.2014-1926. View

Nelson S, Telfer E, Anderson R . The ageing ovary and uterus: new biological insights. Hum Reprod Update. 2012; 19(1):67-83. PMC: 3508627. DOI: 10.1093/humupd/dms043. View

Adhikari D, Liu K . Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev. 2009; 30(5):438-64. DOI: 10.1210/er.2008-0048. View

10.

Burgaya F, Fontana X, Martinez A, Montolio M, Mingorance A, Simo S . Semaphorin 6C leads to GSK-3-dependent growth cone collapse and redistributes after entorhino-hippocampal axotomy. Mol Cell Neurosci. 2006; 33(3):321-34. DOI: 10.1016/j.mcn.2006.08.008. View

11.

John G, Shirley L, Gallardo T, Castrillon D . Specificity of the requirement for Foxo3 in primordial follicle activation. Reproduction. 2007; 133(5):855-63. PMC: 2579775. DOI: 10.1530/REP-06-0051. View

12.

Jiang Z, Hu M, Ma X, Schatten H, Fan H, Wang Z . LKB1 acts as a critical gatekeeper of ovarian primordial follicle pool. Oncotarget. 2016; 7(5):5738-53. PMC: 4868718. DOI: 10.18632/oncotarget.6792. View

13.

Hsueh A . Fertility: the role of mTOR signaling and KIT ligand. Curr Biol. 2014; 24(21):R1040-2. DOI: 10.1016/j.cub.2014.09.033. View

14.

Assou S, Anahory T, Pantesco V, Le Carrour T, Pellestor F, Klein B . The human cumulus--oocyte complex gene-expression profile. Hum Reprod. 2006; 21(7):1705-19. PMC: 2377388. DOI: 10.1093/humrep/del065. View

15.

Dacquin R, Domenget C, Kumanogoh A, Kikutani H, Jurdic P, Machuca-Gayet I . Control of bone resorption by semaphorin 4D is dependent on ovarian function. PLoS One. 2011; 6(10):e26627. PMC: 3202567. DOI: 10.1371/journal.pone.0026627. View

16.

Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y . Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science. 2008; 319(5863):611-3. DOI: 10.1126/science.1152257. View

17.

Zhou Y, Gunput R, Pasterkamp R . Semaphorin signaling: progress made and promises ahead. Trends Biochem Sci. 2008; 33(4):161-70. DOI: 10.1016/j.tibs.2008.01.006. View

18.

Uesaka N, Uchigashima M, Mikuni T, Nakazawa T, Nakao H, Hirai H . Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain. Science. 2014; 344(6187):1020-3. DOI: 10.1126/science.1252514. View

19.

Jagarlamudi K, Liu L, Adhikari D, Reddy P, Idahl A, Ottander U . Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation. PLoS One. 2009; 4(7):e6186. PMC: 2702689. DOI: 10.1371/journal.pone.0006186. View

20.

Regev A, Goldman S, Shalev E . Semaphorin-4D (Sema-4D), the Plexin-B1 ligand, is involved in mouse ovary follicular development. Reprod Biol Endocrinol. 2007; 5:12. PMC: 1838422. DOI: 10.1186/1477-7827-5-12. View