Orchitis: a complication of severe acute respiratory syndrome (SARS)

Abstract

Severe acute respiratory syndrome (SARS) coronavirus has been known to damage multiple organs; however, little is known about its impact on the reproductive system. In the present study, we analyzed the pathological changes of testes from six patients who died of SARS. Results suggested that SARS caused orchitis. All SARS testes displayed widespread germ cell destruction, few or no spermatozoon in the seminiferous tubule, thickened basement membrane, and leukocyte infiltration. The numbers of CD3+ T lymphocytes and CD68+ macrophages increased significantly in the interstitial tissue compared with the control group (P < 0.05). SARS viral genomic sequences were not detected in the testes by in situ hybridization. Immunohistochemistry demonstrated abundant IgG precipitation in the seminiferous epithelium of SARS testes, indicating possible immune response as the cause for the damage. Our findings indicated that orchitis is a complication of SARS. It further suggests that the reproductive functions should be followed and evaluated in recovered male SARS patients.

Fig. 1

Hematoxylin-eosin stain. A) Testis from the control case C01, showing normal morphology. B) Testis from the control case C03, who died of a disease with high fever and was treated with steroids, showing mild basement membrane thickening and vascular congestion. C) Testis from SARS patient S01, showing loss of germ cells, leukocytes infiltration (arrows), and vascular congestion. D) Testis from SARS patient S05, showing basement membrane thickening, peritubular fibrosis, and vascular congestion. Bar = 50 μm

Fig. 2

TUNEL stain. A) Testis from the control case C02, showing a few apoptotic spermatogenetic cells in the tubules (arrows). B) Testis from SARS patient S08, showing increased apoptotic spermatogenetic cells and a few positive Leydig cells (arrows). C) Negative control stain of SARS sample S08 without TdT in the staining process, no positive stain was seen. Bar = 50 μm

Fig. 3

IHC stain with CD68 (A and C) and CD3 (B and D). A) Testis from the control case C01, showing a few CD68+ macrophages in the interstitial tissue (arrows) and no macrophage in the tubule. B) Testis from the control case C02, showing a few CD3+ T lymphocytes in the interstitial tissue (arrows), and no positive cell in the tubule. C) Testis from SARS patient S08, showing CD68+ macrophages in the seminiferous tubules (arrow heads) and the interstitial tissue (arrows). D) Testis from SARS patient S11, showing CD3+ T lymphocytes in the seminiferous tubules (arrow head) and the interstitial tissue (arrows). E) Negative control without primary antibody on the case C01. Bar = 50 μm

Fig. 4

IHC stain with IgG. A) Testis from the control case C01, showing IgG signals in the lumen of blood vessel (arrow). B) Testis from SARS patient S08, showing extensive IgG signals in the seminiferous epithelium, a few positive germ cells (arrow heads) and Sertoli cells (arrows). C) Negative control with isotype control antibody on the serial section of B, no positive signal was seen. Bar = 50 μm

Fig. 5

ISH detection of SARS virus. A) Testis from SARS patient S08 with antisense digoxigenin-labeled RNA probe, showing no positive signals. Insert: SARS lungs stained with the same protocol and probe as a positive control, showing positive type II alveolar cell (arrow) and lymphocytes (arrow head) (will publish separately). B) Testis from SARS patient S08 with sense digoxigenin-labeled RNA probe, showing no positive signals. C) Negative control stain without probe on the same case. Bar = 50 μm