Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures

Man, Limor; Lustgarten-Guahmich, Nicole; Kallinos, Eleni; Redhead-Laconte, Zachary; Liu, Sally; Schattman, Benjamin; Redmond, David; Hancock, Kolbe; Zaninović, Nikica; Schattman, Glenn; Rosenwaks, Zev; James, Daylon

doi:10.1016/j.celrep.2020.108027

Cited by 22 publications

(38 citation statements)

References 58 publications

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“…C-type lectin receptor, CLEC4M allows anchoring of enveloped virus by identifying the glycoproteins structure, which is important, especially contemplating the SARS-CoV-2 pathophysiology. This receptor expression has been found in the ovary and MGCs by single cell RNA sequencing and flow cytometry [13]. In the present study, both microarray analysis and qRT-PCR data showed comparable transcript levels of CLEC4M in MGCs and CGCs of control and PCOS women.…”

Section: Discussionsupporting

confidence: 80%

“…ACE2 and TMPRSS2 [10]. There are reports confirming the presence of ACE2 expression at ovary, uterus, vagina and placenta [9,[11][12][13][14]. In addition to this, expression of other receptors and proteases (BSG, CTSL, FURIN) has been demonstrated in male and female reproductive tissue by several studies by using single cell RNA sequencing approach and by analyzing publically available microarray datasets [4,15].…”

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confidence: 79%

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Ovarian Granulosa Cells From Women With Pcos Express Low Levels of Sars-Cov-2 Receptors and Co-Factors

Naigaonkar

Patil

Joseph

et al. 2021

Preprint

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Purpose: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is global pandemic with more than 3 million deaths so far. Female reproductive tract organs express coronavirus-associated receptors and factors (SCARFs); suggesting they may be susceptible to SARS-CoV-2 infection however the susceptibility of ovary/follicle/oocyte to the same is still elusive. Co-morbidities like obesity, type-2 diabetes mellitus, cardiovascular disease etc. increase the risk of SARS-CoV-2 infection. These features are common in women with polycystic ovary syndrome (PCOS), warranting further scope to study SCARFs expression in ovary of these women. Materials and methods: SCARFs expression in ovary and ovarian tissues of women with PCOS and healthy women was explored by analyzing publically available microarray datasets. Transcript expression of SCARFs were investigated in mural and cumulus granulosa cells (MGCs and CGCs) from control and PCOS women undergoing in vitro fertilization (IVF). Results: Microarray data revealed that ovary expresses all genes necessary for SARS-CoV-2 infection. PCOS women mostly showed down-regulated/unchanged levels of SCARFs. MGCs and CGCs from PCOS women showed lower expression of receptors ACE2, BSG and DPP4 and protease CTSB than in controls. MGCs showed lower expression of protease CTSL in PCOS than in controls. Expression of TMPRSS2 was not detected in both cell types. Conclusions: Human ovarian follicle may be susceptible to SARS-CoV-2 infection. Lower expression of SCARFs in PCOS indicate that the risk of SARS-CoV-2 infection to the ovary may be lesser in these women than controls. This knowledge may help in safe practices at IVF settings in the current pandemic. Keywords: SARS-CoV-2, COVID-19, Ovarian granulosa cells, Oocyte, PCOS, IVF

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 79%

Ovarian Granulosa Cells From Women With Pcos Express Low Levels of Sars-Cov-2 Receptors and Co-Factors

Naigaonkar

Patil

Joseph

et al. 2021

Preprint

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“…1C). This expression pattern is consistent with our previous single-cell RNA sequencing study of granulosa, theca, and stroma cells from antral follicles, in which IGF1R expression was noted in both granulosa and theca cells (28). We also previously used cotransplanted ECs as a vector to convey a continuous paracrine source of antim€ ullerian hormone to improve retention of PrFs in short-term xenografts (25,26).…”

Section: Paracrine Delivery Of Exogenous Igf1 To Xenografted Ovarian Cortical Tissuesupporting

confidence: 89%

“…1C). We previously performed transcriptomic analysis of granulosa and theca cells from human antral follicles (28) and observed a dynamic expression pattern of IGF-binding proteins that are known to modulate bioactivity of IGF1. Indeed, circulating levels of IGF1 can shift dynamically in response to environmental (food intake) or physiological (age) influences (29), thereby necessitating a multitiered mechanism for controlling signal integration at the level of the ovary.…”

Section: Discussionmentioning

confidence: 99%

Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice

et al. 2021

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“…Recently, we and others have used single-cell transcriptomics to reveal the molecular landscape of human ovarian follicular cells from different growing stages [ 9 , 18 , 19 , 20 ]. However, the analysis of oocyte and surrounding GCs from individual antral follicles has not been performed.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptomics Analysis of Human Small Antral Follicles

Fan

Moustakas

Bialecka

et al. 2021

IJMS

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Human ovarian folliculogenesis is a highly regulated and complex process. Characterization of follicular cell signatures during this dynamic process is important to understand follicle fate (to grow, become dominant, or undergo atresia). The transcriptional signature of human oocytes and granulosa cells (GCs) in early-growing and ovulatory follicles have been previously described; however, that of oocytes with surrounding GCs in small antral follicles have not been studied yet. Here, we have generated a unique dataset of single-cell transcriptomics (SmartSeq2) consisting of the oocyte with surrounding GCs from several individual (non-dominant) small antral follicles isolated from adult human ovaries. We have identified two main types of (healthy) follicles, with a distinct oocyte and GC signature. Using the CellphoneDB algorithm, we then investigated the bi-directional ligand–receptor interactions regarding the transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP), wingless-type (MMTV)-integration site (WNT), NOTCH, and receptor tyrosine kinases (RTK) signaling pathways between oocyte and GCs within each antral follicle type. Our work not only revealed the diversity of small antral follicles, but also contributes to fill the gap in mapping the molecular landscape of human folliculogenesis and oogenesis.

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Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures

Cited by 22 publications

References 58 publications

Ovarian Granulosa Cells From Women With Pcos Express Low Levels of Sars-Cov-2 Receptors and Co-Factors

Ovarian Granulosa Cells From Women With Pcos Express Low Levels of Sars-Cov-2 Receptors and Co-Factors

Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice

Single-Cell Transcriptomics Analysis of Human Small Antral Follicles

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