CUMS Promotes the Development of Premature Ovarian Insufficiency Mediated by Nerve Growth Factor and Its Receptor in Rats

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2020 Jul 21

PMID 32685448

Citations 5

Authors

Xiaoyan Fu

Qun Zheng

Ning Zhang

Mingxing Ding

Xiaoming Pan

Wenqian Wang

Haohao Chen

Affiliations

Soon will be listed here.

Abstract

This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF . Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH , and improve the rat ovarian function. Future studies may associate these results with female population.

Citing Articles

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References

Chaves R, Alves A, Duarte A, Araujo V, Celestino J, Matos M . Nerve growth factor promotes the survival of goat preantral follicles cultured in vitro. Cells Tissues Organs. 2010; 192(4):272-82. DOI: 10.1159/000317133. View

Themmen A . Anti-Müllerian hormone: its role in follicular growth initiation and survival and as an ovarian reserve marker. J Natl Cancer Inst Monogr. 2005; (34):18-21. DOI: 10.1093/jncimonographs/lgi026. View

Romero C, Paredes A, Dissen G, Ojeda S . Nerve growth factor induces the expression of functional FSH receptors in newly formed follicles of the rat ovary. Endocrinology. 2002; 143(4):1485-94. DOI: 10.1210/endo.143.4.8711. View

Salas C, Julio-Pieper M, Valladares M, Pommer R, Vega M, Mastronardi C . Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion. J Clin Endocrinol Metab. 2006; 91(6):2396-403. DOI: 10.1210/jc.2005-1925. View

Conway G . Premature ovarian failure. Br Med Bull. 2001; 56(3):643-9. DOI: 10.1258/0007142001903445. View

Dissen G, Garcia-Rudaz C, Paredes A, Mayer C, Mayerhofer A, Ojeda S . Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans. Endocrinology. 2009; 150(6):2906-14. PMC: 2689806. DOI: 10.1210/en.2008-1575. View

Shelling A . Premature ovarian failure. Reproduction. 2010; 140(5):633-41. DOI: 10.1530/REP-09-0567. View

Chaves R, Alves A, Lima L, Matos H, Rodrigues A, Figueiredo J . Role of nerve growth factor (NGF) and its receptors in folliculogenesis. Zygote. 2012; 21(2):187-97. DOI: 10.1017/S0967199412000111. View

Willner P, Towell A, Sampson D, Sophokleous S, Muscat R . Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl). 1987; 93(3):358-64. DOI: 10.1007/BF00187257. View

10.

Reddy P, Adhikari D, Zheng W, Liang S, Hamalainen T, Tohonen V . PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Hum Mol Genet. 2009; 18(15):2813-24. DOI: 10.1093/hmg/ddp217. View

11.

Broer S, Broekmans F, Laven J, Fauser B . Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014; 20(5):688-701. DOI: 10.1093/humupd/dmu020. View

12.

Weng Q, Shi Z, Tukada J, Watanabe G, Taya K . Immunodetection of NGF, trkA, p75 and inhibin alpha-subunit in interstitial cells of golden hamsters treated with hCG. J Reprod Dev. 2009; 55(6):622-8. DOI: 10.1262/jrd.20208. View

13.

Streiter S, Fisch B, Sabbah B, Ao A, Abir R . The importance of neuronal growth factors in the ovary. Mol Hum Reprod. 2015; 22(1):3-17. DOI: 10.1093/molehr/gav057. View

14.

van Helden J, Weiskirchen R . Age-independent anti-Müllerian hormone (AMH) standard deviation scores to estimate ovarian function. Eur J Obstet Gynecol Reprod Biol. 2017; 213:64-70. DOI: 10.1016/j.ejogrb.2017.04.029. View

15.

Gao L, Zhao F, Zhang Y, Wang W, Cao Q . Diminished ovarian reserve induced by chronic unpredictable stress in C57BL/6 mice. Gynecol Endocrinol. 2019; 36(1):49-54. DOI: 10.1080/09513590.2019.1631274. View

16.

Shi Z, Jin W, Watanabe G, Suzuki A, Takahashi S, Taya K . Expression of nerve growth factor (NGF), and its receptors trkA and p75 in ovaries of the cyclic golden hamster (Mesocricetus auratus) and the regulation of their production by luteinizing hormone. J Reprod Dev. 2005; 50(6):605-11. DOI: 10.1262/jrd.50.605. View

17.

Barra R, Cruz G, Mayerhofer A, Paredes A, Lara H . Maternal sympathetic stress impairs follicular development and puberty of the offspring. Reproduction. 2014; 148(2):137-45. DOI: 10.1530/REP-14-0150. View

18.

Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B . ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016; 31(5):926-37. DOI: 10.1093/humrep/dew027. View

19.

Lu J, Wu X, Zhu Q, Li J, Shi L, Wu J . Sex differences in the stress response in SD rats. Behav Brain Res. 2015; 284:231-7. DOI: 10.1016/j.bbr.2015.02.009. View

20.

Yoshida M, Sanbuissyo A, Hisada S, Takahashi M, Ohno Y, Nishikawa A . Morphological characterization of the ovary under normal cycling in rats and its viewpoints of ovarian toxicity detection. J Toxicol Sci. 2009; 34 Suppl 1:SP189-97. DOI: 10.2131/jts.34.s189. View