|
 
 |
| LETTER TO THE EDITOR |
|
| Year : 2021 | Volume
: 6
| Issue : 1 | Page : 20-21 |
|
SARS-CoV-2 and male infertility
Rashmi Baid
Department of Reproductive Medicine, Lilavati Hospital and Research Centre, Mumbai, Maharashtra, India
| Date of Submission | 08-Aug-2021 |
| Date of Acceptance | 15-Feb-2022 |
| Date of Web Publication | 27-Jun-2022 |
Correspondence Address:
Dr. Rashmi Baid
Department of Reproductive Medicine, Lilavati Hospital and Research Centre, Mumbai 400050, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ajiac.ajiac_3_21
How to cite this article:
Baid R. SARS-CoV-2 and male infertility. Afr J Infertil Assist Concept 2021;6:20-1 |
The SARS-CoV-2 pandemic has taken the world by storm with over 160 million reported COVID-19 cases worldwide and more than 3.8 million deaths.[1]
Viruses including hepatitis B and C, mumps, Zika, Ebola, and HIV can dysregulate the male reproductive processes by reducing sperm count and motility, altering sex hormone levels, and negatively influencing spermatogenesis. Preliminary data suggest that the male gonads may be vulnerable to SARS-CoV-2 infection with downstream effects. We discuss how the virus may perpetuate an epidemic of male infertility [Figure 1].
Nearly 80% of the adult COVID-19 patients report fever with as many as 14.7% having high-grade fever.[2] High temperature can cause partial-to-complete spermatogenic arrest, generation of morphologically abnormal sperms, and reduced motility. Animal models have previously reported altered expression of functional sperm proteins including testicular isoform of Na-K-ATPase.[2],[3] Hyperthermia is known to impair the blood–testis barrier, leading to passage of macromolecular substances into the male reproductive organs.[3]
The SARS-CoV-2 virus enters the cell after binding to ACE2 receptors.[1] Cells with different levels of expression of ACE2 may be differently affected by the virus. Once within the cell, it initiates its replication cycle and induces cytotoxicity. All testicular cells, including Leydig cells, Sertoli cells More Details, and spermatogonia, are known to have high expression of ACE2, making them a potential viral target leading to infection and direct cell injury.[4]
Indeed, autopsies of testicular and epididymal samples of patients with COVID-19 disease have shown significantly increased apoptosis, with interstitial edema, red cell exudation, and exaggerated CD3+ and CD68+ response in the testis.[4],[5] This is accompanied by increased inflammatory levels of IL-6, TNF-alpha, and monocyte chemoattractant protein-1. As many as 39% of the patients were found to have oligospermia in one study. IL-6 is known to affect tight junction permeability in Sertoli cells, inhibit meiotic DNA synthesis phases of spermatogenesis, impair motility of sperms, and affect inhibin and transferrin secretion by Sertoli cells.[5]
Substantially reduced sex hormone levels have been reported in COVID-19 patients including total testosterone and free testosterone, especially LH levels have been reported to be markedly higher and have been linked to acute male hypogonadism in COVID-19 subjects.[4],[6] Direct invasion and impairment of the hypothalamo-pituitary dysfunction and the cytokine storm known to accompany the disease could augment this dysfunction. Whether this leads to a persistent sex hormone shift is unknown.[6]
Drug-related injury to the testis could lead to male infertility. A number of drugs used to treat COVID-19 infections have been implicated, including glucocorticoids, antidepressants, and antiviral agents. Corticosteroids are known to cause male infertility through reduced expression of steroidogenic enzymes, apoptosis of Leydig cells, oxidative stress in the testes, and impaired gonadotropin responsiveness.[1] Antidepressants like tricyclic antidepressants and reuptake inhibitors used to treat accompanying depression with COVID-19 disease have been reported to hamper sperm motility and DNA fragmentation.[7] Lopinavir/ritonavir and chloroquine phosphate are known to affect spermatogenesis by inducing oxidative damage to the testis.[8]
In retrospect, the COVID-19 pandemic can hitherto herald an underdiagnosed epidemic of male infertility and as clinicians, it is paramount that we be aware of the consequences.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2022 Feb 5. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022.  |
| 2. | Islam MA, Kundu S, Alam SS, Hossan T, Kamal MA, Hassan R. Prevalence and characteristics of fever in adult and paediatric patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of 17515 patients. PLoS One 2021;16:e0249788. |
| 3. | Thundathil JC, Rajamanickam GD, Kastelic JP, Newton LD. The effects of increased testicular temperature on testis-specific isoform of Na+/K+-ATPase in sperm and its role in spermatogenesis and sperm function. Reprod Domest Anim 2012;47(Suppl. 4):170-7. |
| 4. | Fan C, Lu W, Li K, Ding Y, Wang J. ACE2 expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front Med (Lausanne) 2020;7:563893. |
| 5. | Zhang H, Yin Y, Wang G, Liu Z, Liu L, Sun F. Interleukin-6 disrupts blood–testis barrier through inhibiting protein degradation or activating phosphorylated ERK in Sertoli cells. Sci Rep 2014;4:4260. |
| 6. | Pal R. COVID-19, hypothalamo-pituitary-adrenal axis and clinical implications. Endocrine 2020;68:251-2. |
| 7. | Casilla-Lennon MM, Meltzer-Brody S, Steiner AZ. The effect of antidepressants on fertility. Am J Obstet Gynecol 2016;215:314.e1-5. |
| 8. | Adaramoye OA, Akanni OO, Adewumi OM, Owumi SE. Lopinavir/ritonavir, an antiretroviral drug, lowers sperm quality and induces testicular oxidative damage in rats. Tokai J Exp Clin Med 2015;40:51-7. |
[Figure 1]
|
Search Pubmed for