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Cited by 184Sperm and Testicular FunctionEstrogen and related hormone effectsReproductive biology and impacts on aquatic species

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Estrogen Receptor (ER)α and ERβ Are Both Expressed in Human Ejaculated Spermatozoa: Evidence of Their Direct Interaction with Phosphatidylinositol-3-OH Kinase/Akt Pathway

Aquila, Saveria, Sisci, Diego, Gentile, Mariaelena, Middea, Emilia, Catalano, Stefania, Carpino, Amalia, Rago, Vittoria, Andò, Sebastiano·2004·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2003-031681
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Abstract

Human and animal models have evidenced how estrogen insufficiency is associated with abnormal spermatogenesis and male infertility. We previously demonstrated that estradiol is able to influence both capacitation and acrosome reaction in human ejaculated spermatozoa. It remains to be elucidated whether the biochemical changes induced by estradiol, in a rapid nongenomic way, are mediated by a single estrogen receptor (ER) or by the two ER subtypes, ER alpha and ER beta. In the present study, we have first demonstrated the concomitant expression of ER beta and ER alpha in human ejaculated spermatozoa. By RT-PCR and Southern blot, transcripts of both ERs were detected. Western blot analysis showed ER alpha and ER beta proteins at the same size as the "classical" ERs. The localization of ER alpha and ER beta with the immunocytochemistry shows a differential distribution of the two ER subtypes, the former being prevalently located in the midpiece, but the latter being in the tail. Estradiol has been associated with sperm longevity; however, the mechanism through which estradiol acts in sperm survival was never investigated. Upon estradiol exposure, we observed an enhanced phosphorylation of the proteins involved in the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway like PDK1, Akt, GSK-3, Bcl-2, together with ERK1/2, which was also involved in cell survival signals. Moreover, such phosphorylations were reduced in the presence of ICI 182, 780, addressing the role of estradiol and ERs in sperm survival. For instance we have provided, for the first time, a different interaction of the two ERs with the PI3K/Akt pathway, because ER alpha interacts with the p55 regulatory subunit of PI3K, whereas ER beta interacts with Akt1. However, it still remains to be elucidated whether the functional role of each of the ER subtypes in sperm survival signaling is redundant or distinct.

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Metadata

Authors
Aquila, S., Sisci, D., Gentile, M., Middea, E., Catalano, S., Carpino, A., Rago, V., & Andò, S.
Affiliations
University of Calabria (IT)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2004-03
Volume
89
Issue
3
Pages
1443-1451
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2003-031681
OpenAlex
W1979238526
Cited by
184
References
41
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 5 · 2012: 18
FWCI
13.49
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
Funders
  • Ministero dell’Istruzione, dell’Università e della Ricerca
  • Università della Calabria
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
Keywords
estrogen receptor alpha, estrogen receptor beta, estradiol, sperm survival, PI3K/Akt signaling, non-genomic estrogen signaling, sperm capacitation, acrosome reaction, fulvestrant, AKT1, PDK1, glycogen synthase kinase-3, ERK1/2, Bcl-2
MeSH terms
Cell Survival, Ejaculation, Estradiol, Humans, Male, Proto-Oncogene Proteins, Receptors, Estrogen, Spermatozoa, Blotting, Southern, Blotting, Western, Gene Expression, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-bcl-2, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Reverse Transcriptase Polymerase Chain Reaction, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Estrogen Receptor alpha, Estrogen Receptor beta, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt

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