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Fulltext SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology

Dutta S, Sengupta P

Reprod Sci, 2021 Jan;28(1):23-26.
PMID: 32651900 DOI: 10.1007/s43032-020-00261-z

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men's health and fertility.

Matched MeSH terms: Infertility, Male/pathology*
Fulltext The probable destructive mechanisms behind COVID-19 on male reproduction system and fertility

Moshrefi M, Ghasemi-Esmailabad S, Ali J, Findikli N, Mangoli E, Khalili MA

J Assist Reprod Genet, 2021 Jul;38(7):1691-1708.
PMID: 33977466 DOI: 10.1007/s10815-021-02097-1

PURPOSE: The present study aims to summarize the current understanding of probable mechanisms and claims of adverse effects of SARS-CoV-2 on male fertility potential.
METHODS: Our search was including original articles, reviews, guidelines, letters to the editor, comments on guidelines, and editorials, regarding the male reproductive system. We used the words SARS-CoV-2, coronavirus, severe acute respiratory syndrome coronavirus 2, "2019 ncov," testis, sperm, male factor infertility, fertility treatment, semen, assisted reproductive technology (ART), sexual transmission, and ACE2.
RESULTS: Data showed coronavirus affects men more than women because of more expression of 2019 nCoV receptors (ACE2 and TMPRSS2) in testicular cells. Also, "Bioinformatics Analysis" suggests that sperm production may be damaged, since "Pseudo Time Analysis" has shown disruption in spermatogenesis. "Gene Ontology" (GO) showed an increase in viral reproduction and a decrease in sperm production-related terms. Recently, SARS-COV-2 mRNA and protein were detected in the semen of patients that had recovered from SARS-CoV-2 infection. Therefore, the probable disruption of blood-testis barrier (BTB) in febrile diseases is suspected in the acute phase of the disease enabling viral entry into the testes. Not only is spermatogenesis disturbed, but also disturbs gonadotropin, androgens, and testosterone secretion during SARS-CoV-2 infection. No sexual transmission has been reported yet; however, detection of the virus in semen still makes the sexual transmission an open question.
CONCLUSION: There is a concern that male fertility may be disturbed after the SARS-CoV-2 infection. Therefore, follow-up of the reproductive functions and male fertility may be necessary in recovered cases, especially in aged men.

Matched MeSH terms: Infertility, Male/pathology*
Orlistat reverses intratesticular lactate transport decline and infertility in male obese rats

Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Bakar ABA, Usman UZ, et al.

Reproduction, 2020 12;160(6):863-872.
PMID: 33112813 DOI: 10.1530/REP-20-0381

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague-Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.

Matched MeSH terms: Infertility, Male/pathology
Geographical differences in semen characteristics: Comparing semen parameters of infertile men of the United States and Iraq

Palani A, Sengupta P, Agarwal A, Henkel R

Andrologia, 2020 Apr;52(3):e13519.
PMID: 32003032 DOI: 10.1111/and.13519

The declining trend of male fecundity is a major global health and social concern. Among numerous other confounding factors, variations in male fertility parameters in different regions have repeatedly been suggested to be influenced by geographic locations. The impact of overall lifestyle, behavioural patterns, ethnicity, work stress and associated factors upon health differ greatly between developed and developing countries. These factors, individually or in combination, affect male reproductive functions ensuing the discrepancies in semen qualities in connection with geographic variations. However, reports comparing semen characteristics between developed and developing countries are sparse. The present study finds its novelty in presenting a comparison in semen parameters of infertile men in the United States (n = 76) that fairly represents the population of a highly developed region and Iraq (n = 102), the representative of male populations of a developing region. Samples were collected and analysed according to WHO (WHO laboratory manual for the examination and processing of human semen, WHO; 2010) criteria by means of the Mann-Whitney test. The US population demonstrated lower sperm concentration, total count, and total and progressive sperm motility with a higher seminal total antioxidant capacity (TAC) as compared to the Iraqi population. This report encourages further investigations concerning the confounding factors leading to such alterations in semen qualities between these two geographic areas.

Matched MeSH terms: Infertility, Male/pathology*
Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality

Darbandi M, Darbandi S, Agarwal A, Baskaran S, Dutta S, Sengupta P, et al.

J Assist Reprod Genet, 2019 Feb;36(2):241-253.
PMID: 30382470 DOI: 10.1007/s10815-018-1350-y

PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS male infertility and its management through assisted reproduction technology (ART).

Matched MeSH terms: Infertility, Male/pathology
Morphological and ultrastructural studies of human spermatogonial stem cells from patients with maturation arrest

Mirzapour T, Tengku Ibrahim TAB, Movahedin M, Nowroozi MR

Andrologia, 2017 Sep;49(7).
PMID: 27682317 DOI: 10.1111/and.12700

Destruction of spermatogonial stem cells (SSCs) along the chemotherapy and radiotherapy is one of the side effects of cancer treatments that lead to infertility. In vitro propagation of hSSCs is necessary to obtain an adequate number of cells for successful transplantation. In this study, hSSCs were isolated from testis biopsies of the patients with maturation arrest and proliferated in DMEM in the presence of LIF and bFGF for 5 weeks. The various types of human spermatogonia were identified in culture system and compared with testis tissue using morphological criteria at the ultrastructural level. The results showed that although many various types of spermatogonia were identified, but no remarkable difference was observed between spermatogonial cells in culture system and testis tissue. Electron and light microscopic studies of hSSC colonies did not show differentiated SSCs in the culture system. The results also showed that probably the suitable time for transplanting of SSCs in recipient testis is 2-3 weeks after culture. Because apoptosis which may affect the development of germ cells has not started in colony cells at this time and the population of apoptotic cells are low.

Matched MeSH terms: Infertility, Male/pathology*
Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility

Samanta L, Agarwal A, Swain N, Sharma R, Gopalan B, Esteves SC, et al.

J Urol, 2018 08;200(2):414-422.
PMID: 29530785 DOI: 10.1016/j.juro.2018.03.009

PURPOSE: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility.
MATERIALS AND METHODS: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured.
RESULTS: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele.
CONCLUSIONS: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients.

Matched MeSH terms: Infertility, Male/pathology