COVID-19 Infection Induce miR-371a-3p Upregulation Resulting in Influence on Male Fertility
Heike Goebel,
Barbara Koeditz,
Manuel Huerta,
Ersen Kameri,
Tim Nestler,
Thomas Kamphausen,
Johannes Friemann,
Matthias Hamdorf,
Timo Ohrmann,
Philipp Koehler,
Oliver A. Cornely,
Manuel Montesinos-Rongen,
David Nicol,
Hubert Schorle,
Peter Boor,
Alexander Quaas,
Christian Pallasch,
Axel Heidenreich,
Melanie von Brandenstein
Affiliations
Heike Goebel
Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Barbara Koeditz
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Manuel Huerta
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Ersen Kameri
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Tim Nestler
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Thomas Kamphausen
Institute of Legal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Melatengürtel 60/62, 50823 Cologne, Germany
Johannes Friemann
Klinikum Lüdenscheid, Institute for Pathology, University Hospital Cologne, University of Cologne, Paulmannshöher Straße 14, 58515 Lüdenscheid, Germany
Matthias Hamdorf
Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Timo Ohrmann
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Philipp Koehler
Excellence Center for Medical Mycology (ECMM), Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Oliver A. Cornely
Excellence Center for Medical Mycology (ECMM), Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Manuel Montesinos-Rongen
Department of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
David Nicol
The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
Hubert Schorle
Department of Developmental Pathology, Institute of Pathology, University Bonn Clinics, University of Bonn, 53113 Bonn, Germany
Peter Boor
Department of Pathology, RWTH Aachen University, 52062 Aachen, Germany
Alexander Quaas
Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Christian Pallasch
Excellence Center for Medical Mycology (ECMM), Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Axel Heidenreich
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Melanie von Brandenstein
Clinic and Polyclinic for Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
In December 2019, the first case of COVID-19 was reported and since then several groups have already published that the virus can be present in the testis. To study the influence of SARS-CoV-2 which cause a dysregulation of the androgen receptor (AR) level, thereby leading to fertility problems and inducing germ cell testicular changes in patients after the infection. Formalin-Fixed-Paraffin-Embedded (FFPE) testicular samples from patients who died with or as a result of COVID-19 (n = 32) with controls (n = 6), inflammatory changes (n = 9), seminoma with/without metastasis (n = 11) compared with healthy biopsy samples (n = 3) were analyzed and compared via qRT-PCR for the expression of miR-371a-3p. An immunohistochemical analysis (IHC) and ELISA were performed in order to highlight the miR-371a-3p targeting the AR. Serum samples of patients with mild or severe COVID-19 symptoms (n = 34) were analyzed for miR-371a-3p expression. In 70% of the analyzed postmortem testicular tissue samples, a significant upregulation of the miR-371a-3p was detected, and 75% of the samples showed a reduced spermatogenesis. In serum samples, the upregulation of the miR-371a-3p was also detectable. The upregulation of the miR-371a-3p is responsible for the downregulation of the AR in SARS-CoV-2-positive patients, resulting in decreased spermatogenesis. Since the dysregulation of the AR is associated with infertility, further studies have to confirm if the identified dysregulation is regressive after a declining infection.
