Reduced expression of follicle stimulating hormone receptor mRNA and protein in pregnancies complicated by pre‑eclampsia

Li,Mo; Jia,Yifan; Ling,Yan; Chen,Yilu; Zhang,Lu; Luo,Dan; Lai,Lidan; Guo,Meijun; Zhang,Dalei; Ren,Min; Xu,Hong; Kuang,Haibin

doi:10.3892/mmr.2017.6599

Reduced expression of follicle stimulating hormone receptor mRNA and protein in pregnancies complicated by pre‑eclampsia

Authors:
- Mo Li
- Yifan Jia
- Yan Ling
- Yilu Chen
- Lu Zhang
- Dan Luo
- Lidan Lai
- Meijun Guo
- Dalei Zhang
- Min Ren
- Hong Xu
- Haibin Kuang
View Affiliations

Affiliations: Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Clinical Medicine, School of Queen Mary, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Obstetrics and Gynecology, Jiangxi Province People's Hospital, Nanchang, Jiangxi 330006, P.R. China
Published online on: May 18, 2017 https://doi.org/10.3892/mmr.2017.6599
Pages: 367-372

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Expression and function of the follicle‑stimulating hormone receptor (FSHR) are traditionally thought to be limited to the ovary in females. However, recent studies have indicated that the FSHR is also expressed in endothelial cells of the placental vasculature, and that the haploinsufficiency of the feto‑placental FSHR impaired the growth of the mouse placenta. The aim of the current study was to investigate the placental expression of FSH and FSHR in pregnancies complicated by pre‑eclampsia. Placental tissue samples were collected from 20 pregnancies with pre‑eclampsia and 25 normal pregnancies. Placental FSH and FSHR mRNA levels were measured by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), while FSH, FSHR and CD31 protein expression were examined by immunohistochemistry. Additionally, levels of serum FSH were measured by chemical luminescence immunity assay. The results demonstrated that no significant difference was observed in serum FSH levels and expression levels of placental FSH mRNA and protein between normal pregnancy and pre‑eclampsia. However, RT‑qPCR results indicated that the expression level of FSHR mRNA in pre‑eclamptic placental samples was significantly lower than normal pregnancies. Immunostaining results from normal pregnant samples indicated that the FSHR protein was strongly expressed in the endothelial cells of blood vessels in the chorionic villi, moderately expressed in stromal cells of the villus, but not expressed in trophoblast cells of the term placenta. The staining intensity of FSHR‑positive area was significantly lower in the placental villi of pre‑eclampsia, when compared with the normal control group. In conclusion, expression levels of placental FSHR mRNA and protein are significantly reduced in pregnancies complicated with pre‑eclampsia in the present study. Further studies may investigate whether FSHR could be used as a biomarker for the prediction of pre‑eclampsia.

View Figures

View References

1	Young BC, Levine RJ and Karumanchi SA: Pathogenesis of preeclampsia. Annu Rev Pathol. 5:173–192. 2010. View Article : Google Scholar : PubMed/NCBI
2	Ji L, Brkić J, Liu M, Fu G, Peng C and Wang YL: Placental trophoblast cell differentiation: Physiological regulation and pathological relevance to preeclampsia. Mol Aspects Med. 34:981–1023. 2013. View Article : Google Scholar : PubMed/NCBI
3	Escudero C, Celis C, Saez T, Martin San S, Valenzuela FJ, Aguayo C, Bertoglia P, Roberts JM and Acurio J: Increased placental angiogenesis in late and early onset pre-eclampsia is associated with differential activation of vascular endothelial growth factor receptor 2. Placenta. 35:207–215. 2014. View Article : Google Scholar : PubMed/NCBI
4	Armant DR, Fritz R, Kilburn BA, Kim YM, Nien JK, Maihle NJ, Romero R and Leach RE: Reduced expression of the epidermal growth factor signaling system in preeclampsia. Placenta. 36:270–278. 2015. View Article : Google Scholar : PubMed/NCBI
5	Kappou D, Sifakis S, Androutsopoulos V, Konstantinidou A, Spandidos DA and Papantoniou N: Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia. Placenta. 35:718–723. 2014. View Article : Google Scholar : PubMed/NCBI
6	Jiang X, Liu H, Chen X, Chen PH, Fischer D, Sriraman V, Yu HN, Arkinstall S and He X: Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc Natl Acad Sci USA. 109:12491–12496. 2012. View Article : Google Scholar : PubMed/NCBI
7	Bernard DJ, Fortin J, Wang Y and Lamba P: Mechanisms of FSH synthesis: What we know, what we don't, and why you should care. Fertil Steril. 93:2465–2485. 2010. View Article : Google Scholar : PubMed/NCBI
8	Stilley JA, Christensen DE, Dahlem KB, Guan R, Santillan DA, England SK, Al-Hendy A, Kirby PA and Segaloff DL: FSH receptor (FSHR) expression in human extragonadal reproductive tissues and the developing placenta, and the impact of its deletion on pregnancy in mice. Biol Reprod. 91:742014. View Article : Google Scholar : PubMed/NCBI
9	Mizrachi D and Shemesh M: Follicle-stimulating hormone receptor and its messenger ribonucleic acid are present in the bovine cervix and can regulate cervical prostanoid synthesis. Biol Reprod. 61:776–784. 1999. View Article : Google Scholar : PubMed/NCBI
10	Celik O, Tagluk ME, Hascalik S, Elter K, Celik N and Aydin NE: Spectrotemporal changes in electrical activity of myometrium due to recombinant follicle-stimulating hormone preparations follitropin alfa and beta. Fertil Steril. 90:(Suppl 4). S1348–S1356. 2008. View Article : Google Scholar
11	Hascalik S, Celik O, Tagluk ME, Yildirim A and Aydin NE: Effects of highly purified urinary FSH and human menopausal FSH on uterine myoelectrical dynamics. Mol Hum Reprod. 16:200–206. 2010. View Article : Google Scholar : PubMed/NCBI
12	Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, Zaidi S, Zhu LL, Yaroslavskiy BB, Zhou H, et al: FSH directly regulates bone mass. Cell. 125:247–260. 2006. View Article : Google Scholar : PubMed/NCBI
13	Zhu LL, Blair H, Cao J, Yuen T, Latif R, Guo L, Tourkova IL, Li J, Davies TF, Sun L, et al: Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proc Natl Acad Sci USA. 109:14574–14579. 2012. View Article : Google Scholar : PubMed/NCBI
14	Liu S, Cheng Y, Fan M, Chen D and Bian Z: FSH aggravates periodontitis-related bone loss in ovariectomized rats. J Dent Res. 89:366–371. 2010. View Article : Google Scholar : PubMed/NCBI
15	Stilley JA, Guan R, Duffy DM and Segaloff DL: Signaling through FSH receptors on human umbilical vein endothelial cells promotes angiogenesis. J Clin Endocrinol Metab. 99:E813–E820. 2014. View Article : Google Scholar : PubMed/NCBI
16	Fisher TE, Molskness TA, Villeda A, Zelinski MB, Stouffer RL and Xu J: Vascular endothelial growth factor and angiopoietin production by primate follicles during culture is a function of growth rate, gonadotrophin exposure and oxygen milieu. Hum Reprod. 28:3263–3270. 2013. View Article : Google Scholar : PubMed/NCBI
17	Radu A, Pichon C, Camparo P, Antoine M, Allory Y, Couvelard A, Fromont G, Hai MT and Ghinea N: Expression of follicle-stimulating hormone receptor in tumor blood vessels. N Engl J Med. 363:1621–1630. 2010. View Article : Google Scholar : PubMed/NCBI
18	Planeix F, Siraj MA, Bidard FC, Robin B, Pichon C, Sastre-Garau X, Antoine M and Ghinea N: Endothelial follicle-stimulating hormone receptor expression in invasive breast cancer and vascular remodeling at tumor periphery. J Exp Clin Cancer Res. 34:122015. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Faiman C, Ryan RJ, Zwirek SJ and Rubin ME: Serum FSH and HCG during human pregnancy and puerperium. J Clin Endocrinol Metab. 28:1323–1329. 1968. View Article : Google Scholar : PubMed/NCBI
21	Penny R, Olambiwonnu NO and Frasier SD: Follicle stimulating hormone (FSH) and luteinizing hormone-human chorionic gonadotropin (LH-HCG) concentrations in paired maternal and cord sera. Pediatrics. 53:41–47. 1974.PubMed/NCBI
22	Parlow AF, Daane TA and Dignam WJ: On the concentration of radioimmunoassayable FSH circulating in blood throughout human pregnancy. J Clin Endocrinol Metab. 31:213–214. 1970. View Article : Google Scholar : PubMed/NCBI
23	Jaffe RB, Lee PA and Midgley AR Jr: Serum gonadotropins before, at the inception of, and following human pregnancy. J Clin Endocrinol Metab. 29:1281–1283. 1969. View Article : Google Scholar : PubMed/NCBI
24	Winn VD, Haimov-Kochman R, Paquet AC, Yang YJ, Madhusudhan MS, Gormley M, Feng KT, Bernlohr DA, McDonagh S, Pereira L, et al: Gene expression profiling of the human maternal-fetal interface reveals dramatic changes between midgestation and term. Endocrinology. 148:1059–1079. 2007. View Article : Google Scholar : PubMed/NCBI
25	Dezso Z, Nikolsky Y, Sviridov E, Shi W, Serebriyskaya T, Dosymbekov D, Bugrim A, Rakhmatulin E, Brennan RJ, Guryanov A, et al: A comprehensive functional analysis of tissue specificity of human gene expression. BMC Biol. 6:492008. View Article : Google Scholar : PubMed/NCBI
26	Eyster KM, Klinkova O, Kennedy V and Hansen KA: Whole genome deoxyribonucleic acid microarray analysis of gene expression in ectopic versus eutopic endometriusm. Fertil Steril. 88:1505–1533. 2007. View Article : Google Scholar : PubMed/NCBI
27	Reisinger K, Baal N, McKinnon T, Münstedt K and Zygmunt M: The gonadotropins: Tissue-specific angiogenic factors? Mol Cell Endocrinol. 269:65–80. 2007. View Article : Google Scholar : PubMed/NCBI
28	Fatima LA, Evangelista MC, Silva RS, Cardoso AP, Baruselli PS and Papa PC: FSH up-regulates angiogenic factors in luteal cells of buffaloes. Domest Anim Endocrinol. 45:224–237. 2013. View Article : Google Scholar : PubMed/NCBI
29	Siraj MA, Pichon C, Radu A and Ghinea N: Endothelial follicle stimulating hormone receptor in primary kidney cancer correlates with subsequent response to sunitinib. J Cell Mol Med. 16:2010–2016. 2012. View Article : Google Scholar : PubMed/NCBI
30	Siraj A, Desestret V, Antoine M, Fromont G, Huerre M, Sanson M, Camparo P, Pichon C, Planeix F, Gonin J, et al: Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases. BMC Cancer. 13:2462013. View Article : Google Scholar : PubMed/NCBI
31	Renner M, Goeppert B, Siraj MA, Radu A, Penzel R, Wardelmann E, Lehner B, Ulrich A, Stenzinger A, Warth A, et al: Follicle-stimulating hormone receptor expression in soft tissue sarcomas. Histopathology. 63:29–35. 2013. View Article : Google Scholar : PubMed/NCBI
32	Chen Y, Tong XH, Sun CJ and Zhang WY: Study of follicle-stimulating hormone receptor and tyrosine hydroxylase polymorphisms and pre-eclampsia in Chinese Han population. Zhonghua Yi Xue Za Zhi. 90:1213–1215. 2010.(In Chinese). PubMed/NCBI
33	Katari S, Wood-Trageser MA, Jiang H, Kalynchuk E, Muzumdar R, Yatsenko SA and Rajkovic A: Novel inactivating mutation of the FSH receptor in two siblings of Indian origin with premature ovarian failure. J Clin Endocrinol Metab. 100:2154–2157. 2015. View Article : Google Scholar : PubMed/NCBI
34	Wu XQ, Xu SM, Liu JF, Bi XY, Wu YX and Liu J: Association between FSHR polymorphisms and polycystic ovary syndrome among Chinese women in north China. J Assist Reprod Genet. 31:371–377. 2014. View Article : Google Scholar : PubMed/NCBI
35	Ma L, Chen Y, Mei S, Liu C, Ma X, Li Y, Jiang Y, Ha L and Xu X: Single nucleotide polymorphisms in premature ovarian failure-associated genes in a Chinese Hui population. Mol Med Rep. 12:2529–2538. 2015.PubMed/NCBI
36	Brownfoot FC, Tong S, Hannan NJ, Hastie R, Cannon P, Tuohey L and Kaitu'u-Lino TJ: YC-1 reduces placental sFlt-1 and soluble endoglin production and decreases endothelial dysfunction: A possible therapeutic for preeclampsia. Mol Cell Endocrinol. 413:202–208. 2015. View Article : Google Scholar : PubMed/NCBI
37	Wang J, Tao YM, Cheng XY, Zhu TF, Chen ZF, Yao H and Su LX: Vascular endothelial growth factor affects dendritic cell activity in hypertensive disorders of pregnancy. Mol Med Rep. 12:3781–3786. 2015.PubMed/NCBI