The high rate of SARS-CoV-2 infection poses a serious threat to public health. Previous studies have suggested that SARS-CoV-2 can infect human ovary, the core organ of the female reproductive system. However, it remains unclear which type of ovarian cells are easily infected by SARS-CoV-2 and whether ovarian infectivity differs from puberty to menopause. In this study, public datasets containing bulk and single-cell RNA-Seq data derived from ovarian tissues were analyzed to demonstrate the mRNA expression and protein distribution of the two key entry receptors for SARS-CoV-2-angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2). Furthermore, an immunohistochemical study of ACE2 and TMPRSS2 in human ovaries of different ages was conducted. Differentially expressed gene (DEG) analysis of ovaries of different ages and with varying ovarian reserves was conducted to explore the potential functions of ACE2 and TMPRSS2 in the ovary. The analysis of the public datasets indicated that the co-expression of ACE2 and TMPRSS2 was observed mostly in oocytes and partially in granulosa cells. However, no marked difference was observed in ACE2 or TMPRSS2 expression between young and old ovaries and ovaries with low and high reserves. Correspondingly, ACE2 and TMPRSS2 were detected in the human ovarian cortex and medulla, especially in oocytes of different stages, with no observed variations in their expression level in ovaries of different ages, which was consistent with the results of bioinformatic analyses. Remarkably, DEG analysis showed that a series of viral infection-related pathways were more enriched in ACE2-positive ovarian cells than in ACE2-negative ovarian cells, suggesting that SARS-CoV-2 may potentially target specific ovarian cells and affect ovarian function. However, further fundamental and clinical research is still needed to monitor the process of SARS-CoV-2 entry into ovarian cells and the long-term effects of SARS-CoV-2 infection on the ovarian function in recovered females.
Subject(s)Angiotensin-Converting Enzyme 2/genetics , Ovary/cytology , Ovary/physiology , SARS-CoV-2/pathogenicity , Serine Endopeptidases/genetics , Adult , Age Factors , Aged , Angiotensin-Converting Enzyme 2/metabolism , Animals , Female , Gene Expression Regulation , Humans , Macaca fascicularis , Menopause , Middle Aged , Ovary/virology , Puberty , RNA, Messenger , Serine Endopeptidases/metabolism , Virus Internalization , Young Adult
There has been significant concern regarding fertility and reproductive outcomes during the SARS-CoV2 pandemic. Recent data suggests a high concentration of SARS-Cov2 receptors, ACE2 or TMPRSS2, in nasal epithelium and cornea, which explains person-to-person transmission. We investigated the prevalence of SARS-CoV2 receptors among reproductive tissues by exploring the single-cell sequencing datasets from uterus, myometrium, ovary, fallopian tube, and breast epithelium. We did not detect significant expression of either ACE2 or TMPRSS2 in the normal human myometrium, uterus, ovaries, fallopian tube, or breast. Furthermore, none of the cell types in the female reproductive organs we investigated, showed the co-expression of ACE2 with proteases, TMPRSS2, Cathepsin B (CTSB), and Cathepsin L (CTSL) known to facilitate the entry of SARS2-CoV2 into the host cell. These results suggest that myometrium, uterus, ovaries, fallopian tube, and breast are unlikely to be susceptible to infection by SARS-CoV2.
Subject(s)Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Cathepsin B/genetics , Cathepsin L/genetics , SARS-CoV-2/genetics , Serine Endopeptidases/genetics , Angiotensin-Converting Enzyme 2/metabolism , Breast/metabolism , Breast/virology , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Epithelium/metabolism , Epithelium/virology , Fallopian Tubes/metabolism , Fallopian Tubes/virology , Female , Fertility/genetics , High-Throughput Nucleotide Sequencing , Humans , Myometrium/metabolism , Myometrium/virology , Ovary/metabolism , Ovary/virology , RNA, Viral/genetics , RNA, Viral/isolation & purification , Reproductive Tract Infections/genetics , Reproductive Tract Infections/virology , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Single-Cell Analysis , Uterus/metabolism , Uterus/virology
Since the emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in December 2019, it has rapidly spread across many countries and it has become a crucial global health concern. Furthermore, SARS-CoV-2 infection not only effect on respiratory system, but on reproductive system of human. However, there has been not any review described the transmission paths and effects of SARS-CoV-2 infection on human reproductive system, systematically. In order to describe the transmission paths of SARS-CoV-2, effect on the male/female reproductive system of SARS-CoV-2 and some successful prevention measures. We would like to review effect of SARS-CoV-2 on reproductive system. To conclude, SARS-CoV-2 infection might damage to male reproductive system via ACE2 receptor mediating and male patients were reportedly slightly more affected than women by SARS-CoV-2 infections.
Subject(s)COVID-19/complications , Genitalia/virology , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/metabolism , Female , Genital Diseases, Female/virology , Genital Diseases, Male/virology , Global Health , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Ovary/virology , Pregnancy , Semen/virology , Sex Factors , Testis/virology , Uterus/virology
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a severe global pandemic, affecting mostly the respiratory system. Understandably, attention is also being directed towards the urogenital tract. In this work, expression patterns of various host molecules possibly involved in viral entry and replication were investigated in human female and male reproductive systems by inquiring online repositories, including the Human Protein Atlas, GTEx, FANTOM5. Our findings highlight that male reproductive tissues could be targeted by SARS-CoV-2, particularly the testis since it co-expresses the receptor (ACE2) and the protease (TMPRSS) needed for viral entry. We hypothesized that SARS-CoV-2 infection could have repercussions on the fertility status of male individuals Potential infectivity of SARS-CoV-2 in reproductive tissues should be considered in reproductive medicine and management of in vitro fertilization in present and future generations.
Subject(s)Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Ovary/virology , Pneumonia, Viral/epidemiology , Testis/virology , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/genetics , Coronavirus Infections/virology , Female , Humans , Male , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , Reproduction/physiology , SARS-CoV-2
OBJECTIVE: To identify cell types in the male and female reproductive systems at risk for SARS-CoV-2 infection because of the expression of host genes and proteins used by the virus for cell entry. DESIGN: Descriptive analysis of transcriptomic and proteomic data. SETTING: Academic research department and clinical diagnostic laboratory. PATIENT(S): Not applicable (focus was on previously generated gene and protein expression data). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification of cell types coexpressing the key angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) genes and proteins as well as other candidates potentially involved in SARS-CoV-2 cell entry. RESULT(S): On the basis of single-cell RNA sequencing data, coexpression of ACE2 and TMPRSS2 was not detected in testicular cells, including sperm. A subpopulation of oocytes in nonhuman primate ovarian tissue was found to express ACE2 and TMPRSS2, but coexpression was not observed in ovarian somatic cells. RNA expression of TMPRSS2 in 18 samples of human cumulus cells was shown to be low or absent. There was general agreement between publicly available bulk RNA and protein datasets in terms of ACE2 and TMPRSS2 expression patterns in testis, ovary, endometrial, and placental cells. CONCLUSION(S): These analyses suggest that SARS-CoV-2 infection is unlikely to have long-term effects on male and female reproductive function. Although the results cannot be considered definitive, they imply that procedures in which oocytes are collected and fertilized in vitro are associated with very little risk of viral transmission from gametes to embryos and may indeed have the potential to minimize exposure of susceptible reproductive cell types to infection in comparison with natural conception.
Subject(s)Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Fertility/physiology , Gene Expression Regulation, Viral/physiology , Pneumonia, Viral/metabolism , Reproduction/physiology , Virus Internalization , Adolescent , Adult , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/genetics , COVID-19 , Cell Line , Coronavirus Infections/genetics , Female , Humans , Macaca fascicularis , Male , Ovary/cytology , Ovary/metabolism , Ovary/virology , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Pregnancy , Proteomics/methods , SARS-CoV-2 , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/genetics , Testis/cytology , Testis/metabolism , Testis/virology , Transcriptome/physiology , Young Adult
This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor-binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, Î³-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.