Expression of G-Protein-Coupled Estrogen Receptor () in Whole Testicular Tissue and Laser-Capture Microdissected Testicular Compartments of Men with Normal and Aberrant Spermatogenesis

Overview

Journal Biology (Basel)

Publisher MDPI

Specialty Biology

Date 2022 Mar 26

PMID 35336747

Authors

Renata Walczak-Jedrzejowska

Ewa Forma

Elzbieta Oszukowska

Magdalena Brys

Katarzyna Marchlewska

Krzysztof Kula

Jolanta Slowikowska-Hilczer

Affiliations

Soon will be listed here.

Abstract

In this study, we retrospectively investigated expression in biopsies of azoospermic men with complete (obstructive azoospermia-OA) and aberrant spermatogenesis (nonobstructive azoospermia-NOA). Each biopsy was histologically evaluated with morphometry. The testicular expression was analyzed by the immunohistochemistry and RT-PCR technique in the whole testicular tissue and in seminiferous tubules and Leydig cells after laser-capture microdissection. In laser-microdissected compartments, we also analyzed transcriptional expression of selected Leydig (, HSD17B3, ) and Sertoli cell (, , ) function markers. Immunohistochemical staining revealed expression of in the cytoplasm of Leydig and Sertoli cells. Its stronger intensity was observed in Sertoli cells of NOA biopsies. The RT-PCR analysis of the mRNA level unequivocally showed its increased expression in seminiferous tubules (i.e., Sertoli cells), not Leydig cells in NOA biopsies. This increased expression correlated positively with the transcriptional level of -a marker of Sertoli cell immaturity, as well as FSH serum level in NOA but not in the OA group. Our results clearly demonstrate altered expression in testes with primary spermatogenic impairment that might be related to Sertoli cell maturity/function.

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References

Rago V, Romeo F, Giordano F, Maggiolini M, Carpino A . Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes. Reprod Biol Endocrinol. 2011; 9:135. PMC: 3200171. DOI: 10.1186/1477-7827-9-135. View

Pentikainen V, Erkkila K, Suomalainen L, Parvinen M, Dunkel L . Estradiol acts as a germ cell survival factor in the human testis in vitro. J Clin Endocrinol Metab. 2000; 85(5):2057-67. DOI: 10.1210/jcem.85.5.6600. View

Paduch D, Hilz S, Grimson A, Schlegel P, Jedlicka A, Wright W . Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome. PLoS One. 2019; 14(5):e0216586. PMC: 6508736. DOI: 10.1371/journal.pone.0216586. View

Han Y, Feng H, Sandlow J, Haines C . Comparing expression of progesterone and estrogen receptors in testicular tissue from men with obstructive and nonobstructive azoospermia. J Androl. 2008; 30(2):127-33. DOI: 10.2164/jandrol.108.005157. View

Sandner F, Welter H, Schwarzer J, Kohn F, Urbanski H, Mayerhofer A . Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility. Andrology. 2014; 2(5):695-701. PMC: 4134690. DOI: 10.1111/j.2047-2927.2014.00243.x. View

Kim S, Lee B, Oh A, Park S, Lee H, Seo J . Clinical, Hormonal, and Genetic Evaluation of Idiopathic Nonobstructive Azoospermia and Klinefelter Syndrome Patients. Cytogenet Genome Res. 2018; 153(4):190-197. DOI: 10.1159/000487039. View

Misiakiewicz-Has K, Pilutin A, Wiszniewska B . Influence of hormonal imbalance on the integrity of seminiferous epithelium in the testes of adult rats chronically exposed to letrozole and rats exposed to soya isoflavones during the prenatal period, lactation, and up to sexual maturity. Reprod Biol. 2021; 21(4):100562. DOI: 10.1016/j.repbio.2021.100562. View

Araujo F, Oliveira C, Reis A, Del Puerto H, Martins A, Reis F . Expression of the proto-oncogene c-fos and the immunolocalization of c-fos, phosphorylated c-fos and estrogen receptor beta in the human testis. Histol Histopathol. 2009; 24(12):1515-22. DOI: 10.14670/HH-24.1515. View

Witkowski M, Pardyak L, Pawlicki P, Galuszka A, Profaska-Szymik M, Plachno B . The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways. Int J Mol Sci. 2021; 22(13). PMC: 8269005. DOI: 10.3390/ijms22137131. View

10.

Adamczewska D, Slowikowska-Hilczer J, Marchlewska K, Walczak-Jedrzejowska R . Features of gonadal dysgenesis and Leydig cell impairment in testes with Sertoli cell-only syndrome. Folia Histochem Cytobiol. 2020; 58(2):73-82. DOI: 10.5603/FHC.a2020.0008. View

11.

Zimmerman M, Budish R, Kashyap S, Lindsey S . GPER-novel membrane oestrogen receptor. Clin Sci (Lond). 2016; 130(12):1005-16. PMC: 5125080. DOI: 10.1042/CS20160114. View

12.

Payne A, Perkins L, Georgiou M, Quinn P . Intratesticular site of aromatase activity and possible function of testicular estradiol. Steroids. 1987; 50(4-6):435-48. DOI: 10.1016/0039-128x(87)90030-4. View

13.

Dostalova P, Zatecka E, Dvorakova-Hortova K . Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen Receptors in Male Reproduction. Int J Mol Sci. 2017; 18(5). PMC: 5454817. DOI: 10.3390/ijms18050904. View

14.

Ebling F, Brooks A, Cronin A, Ford H, Kerr J . Estrogenic induction of spermatogenesis in the hypogonadal mouse. Endocrinology. 2000; 141(8):2861-9. DOI: 10.1210/endo.141.8.7596. View

15.

Pelletier G, El-Alfy M . Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab. 2001; 85(12):4835-40. DOI: 10.1210/jcem.85.12.7029. View

16.

Amir S, Shah S, Mamoulakis C, Docea A, Kalantzi O, Zachariou A . Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review. Int J Environ Res Public Health. 2021; 18(4). PMC: 7913912. DOI: 10.3390/ijerph18041464. View

17.

Chimento A, Sirianni R, Casaburi I, Ruggiero C, Maggiolini M, Ando S . 17β-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line. Mol Cell Endocrinol. 2012; 355(1):49-59. DOI: 10.1016/j.mce.2012.01.017. View

18.

Haverfield J, Ham S, Brown K, Simpson E, Meachem S . Teasing out the role of aromatase in the healthy and diseased testis. Spermatogenesis. 2012; 1(3):240-249. PMC: 3271666. DOI: 10.4161/spmg.1.3.18037. View

19.

Guminska A, Slowikowska-Hilczer J, Kuzanski W, Sosnowski M, Oszukowska E, Marchlewska K . Features of impaired seminiferous tubule differentiation are associated with germ cell neoplasia in adult men surgically treated in childhood because of cryptorchidism. Folia Histochem Cytobiol. 2008; 45 Suppl 1:S163-8. View

20.

Mauduit C, Hamamah S, Benahmed M . Stem cell factor/c-kit system in spermatogenesis. Hum Reprod Update. 1999; 5(5):535-45. DOI: 10.1093/humupd/5.5.535. View