Human eggs, zygotes, and embryos express the receptor angiotensin 1-converting enzyme 2 and transmembrane serine protease 2 protein necessary for severe acute respiratory syndrome coronavirus 2 infection

Rajput, Sandeep; Logsdon, Deirdre M.; Kile, Becca; Engelhorn, Heidi J.; Goheen, Ben; Khan, Shaihla A.; Swain, Jason E.; McCormick, S.; Schoolcraft, William B.; Yuan, Ye; Krisher, Rebecca L.

doi:10.1016/j.xfss.2020.12.005

Cited by 24 publications

(32 citation statements)

References 49 publications

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“…In this study, the expression of TMPRSS2, CD147, and CTSL was also documented in these ovarian cells as factors involved in SARS-CoV-2 infection (40). Therefore, our current findings showing the rapid and dramatic induction of ACE2 expression, together with the findings from the previous study (40), offer a compelling possibility that the ovary could be a target of SARS-CoV-2, being particularly vulnerable during the periovulatory period. In the scenario of SARS-CoV-2 infection in the ovary, this virus could have a negative impact on female fertility, not only by blocking the physiological action of ACE2 necessary for oocyte maturation, ovulation, and corpus luteum formation, but also by destroying mature oocytes and ovulatory follicles.…”

Section: Discussionsupporting

confidence: 72%

“…With the current global challenge of COVID-19, our findings take on another level of significance, since ACE2 serves as a primary entry receptor for SARS-CO-2. A recent study reported ACE2 expression in oocytes, cumulus cells, and granulosa cells collected from patients at the time of IVF procedure (40). In this study, the expression of TMPRSS2, CD147, and CTSL was also documented in these ovarian cells as factors involved in SARS-CoV-2 infection (40).…”

Section: Discussionsupporting

confidence: 62%

“…A recent study reported ACE2 expression in oocytes, cumulus cells, and granulosa cells collected from patients at the time of IVF procedure (40). In this study, the expression of TMPRSS2, CD147, and CTSL was also documented in these ovarian cells as factors involved in SARS-CoV-2 infection (40). Therefore, our current findings showing the rapid and dramatic induction of ACE2 expression, together with the findings from the previous study (40), offer a compelling possibility that the ovary could be a target of SARS-CoV-2, being particularly vulnerable during the periovulatory period.…”

Section: Discussionmentioning

confidence: 99%

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Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary

Choi

Jeon

Brännström

et al. 2021

Fertility and Sterility

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Objective To determine the temporal expression of ACE2, a receptor for SARS-COV-2, in dominant follicles across the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC). Design Experimental prospective clinical study and laboratory-based investigation. Setting University Medical Center and private IVF center. Patients Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing IVF. Intervention (s) Administration of hCG and harvesting of preovulatory/ovulatory follicles by timed laparoscopy and collection of granulosa/lutein cells and cumulus cells at the time of oocyte retrieval. Main Outcome Measures Expression and localization of ACE2 in granulosa cells and dominant follicles collected across the periovulatory period of the menstrual cycle and in hGLC using qPCR, immunoblotting, and immunohistochemistry. Results ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after hCG administration. ACE2 expression was higher in cumulus cells than granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures, but the increase was inhibited by both RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor), but not by AG1478 (an EGF-receptor tyrosine kinase inhibitor) or by dexamethasone. Conclusions The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also implicate the possible impact of COVID-19 in a vital cyclic event of ovarian function, thus women's overall reproductive health. However, SAR-COV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary

Choi

Jeon

Brännström

et al. 2021

Fertility and Sterility

View full text Add to dashboard Cite

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“…Based on the available transcriptomic data, co-expression of ACE2 and TMPRSS2 is also observed in oocytes, but the possible impact of SARS-CoV-2 on reproduction is unknown. Indeed, there is no evidence at present that contamination of female reproductive cells can occur in vivo or in vitro in an ART setting ( Rajput et al , 2021 ). One study evaluated viral mRNA in 16 oocytes from two SARS-CoV-2-positive women and all samples were negative ( Barragan et al , 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Risk of contamination of semen, vaginal secretions, follicular fluid and ovarian medulla with SARS-CoV-2 in patients undergoing ART

et al. 2021

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STUDY QUESTION Can severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA be detected in the reproductive tract of asymptomatic patients undergoing ART? SUMMARY ANSWER SARS-CoV-2 mRNA is not detectable in semen, follicular fluid, vaginal secretions or residual medulla from ovarian tissue cryopreservation procedures in asymptomatic patients who undergo ART, irrespective of the results of a triage questionnaire and a nasopharyngeal SARS-CoV-2 RNA detection test. WHAT IS KNOWN ALREADY The SARS-CoV-2 pandemic had a huge impact on the activities of fertility clinics. Although some studies reported the presence of SARS-CoV-2 mRNA in the reproductive system during or after acute COVID-19 symptomatic infections, uncertainties remain regarding the presence of viral mRNA in the reproductive material and follicular fluid of asymptomatic patients undergoing ART. STUDY DESIGN, SIZE, DURATION An observational cohort trial of residual material samples including semen, follicular fluid, vaginal secretions and ovarian medulla was conducted during the second pandemic wave in Brussels from September 2020 to April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients who underwent ART (IUI, IVF/ICSI, oocyte and ovarian tissue cryopreservation) responded to a triage questionnaire at the beginning and end of the cycle and underwent nasopharyngeal swab collection for SARS-CoV-2 RNA detection by RT-PCR before the procedure according to standard recommendations. For semen analysis, only the questionnaire was requested the day before the sample collection. The ART cycles of patients with positive nasopharyngeal SARS-CoV-2 RNA detection tests and/or questionnaires were cancelled except for those that could not be postponed. After providing informed consent, swabs on residual materials were collected the day of the oocyte, ovarian tissue or semen collection and were processed for RT-qPCR. MAIN RESULTS AND THE ROLE OF CHANCE A total of 394 samples from 291 patients were analysed. Amongst them, 20 samples were obtained from patients with a positive questionnaire but negative nasopharyngeal SARS-CoV-2 test and 20 others were from patients with a positive nasopharyngeal SARS-CoV-2 test. The remaining samples were collected from patients with a negative or unknown nasopharyngeal SARS-CoV-2 test and/or a negative or unknown triage questionnaire. Viral RNA for SARS-CoV-2 was undetectable in all of the samples. LIMITATIONS, REASONS FOR CAUTION Considering the cancellation policy, only a limited number of samples from patients with positive triage questionnaires or nasopharyngeal SARS-CoV-2 tests were included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS The study suggested that there was no risk of reproductive tract contamination by SARS-CoV-2 in asymptomatic patients, irrespective of the results from a triage questionnaire or nasopharyngeal SARS-CoV-2 test. The results suggested that no additional measures to prevent staff or cross-patient contamination need to be implemented in the IVF and andrology laboratories. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Université Libre de Bruxelles and by a grant from Ferring. A.D. and I.D. received a grant from Ferring for the study. The authors have no other conflict of interest to declare related to this study. TRIAL REGISTRATION NUMBER N/A.

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“…In male, emerging evidence demonstrated that the SARS-CoV-2 was able to infect the testis, leading to spermatogenic damages and semen impairments [ 4 , 5 ]. In female, studies have demonstrated the expression of SARS-CoV-2-interacting proteins, ACE2, TMPRSS2, and CD147, in human oocytes and blastocysts [ 6 , 7 ]. Barragan et al have detected the viral RNA for gene N of SARS-CoV-2 in the oocytes from two SARS-CoV-2 positive women [ 8 ], suggesting that the oocytes of SARS-CoV-2 positive women may be exposed to these viral RNA and protein products.…”

Section: Introductionmentioning

confidence: 99%

The N501Y Mutation of SARS-CoV-2 Spike Protein Impairs Spindle Assembly in Mouse Oocytes

et al. 2021

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Human eggs, zygotes, and embryos express the receptor angiotensin 1-converting enzyme 2 and transmembrane serine protease 2 protein necessary for severe acute respiratory syndrome coronavirus 2 infection

Cited by 24 publications

References 49 publications

Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary

Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary

Risk of contamination of semen, vaginal secretions, follicular fluid and ovarian medulla with SARS-CoV-2 in patients undergoing ART

The N501Y Mutation of SARS-CoV-2 Spike Protein Impairs Spindle Assembly in Mouse Oocytes

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