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The Involvement of Lumican in Human Ovulatory Processes

  • Reproductive Biology: Original Article
  • Published:
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Abstract

Based on a previous global transcriptome sequencing project, we hypothesized that Lumican (LUM) might play a role in ovulatory processes. We sought to determine LUM gene expression under various conditions in human preovulatory follicles. The in vitro expression of LUM mRNA in mural (MGCs) and cumulus (CGCs) granulosa cells was characterized using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical staining was used to identify human LUM expression in follicles at different developmental stages. Cell signaling studies were performed by treating human MGCs with human chorionic gonadotropin (hCG) and both, different stimulators and inhibitors to determine their effect on LUM expression by using qRT-PCR. Cell confluence studies were carried out to study the correlation between LUM expression and follicle cell proliferation. Follicular MGCs and CGCs of women undergoing in vitro fertilization (IVF) procedures due to endometriosis were analyzed for differences in LUM expression patterns by qRT-PCR. LUM mRNA expression was significantly higher in MGCs as compared to CGCs. In CGCs, LUM mRNA was higher in mature metaphase II (MII) oocytes than in germinal vesicle (GV) and metaphase I (MI) oocytes. LUM expression was significantly upregulated in response to hCG in cultured MGCs. Immunohistochemistry of human ovaries revealed LUM was mostly present in MGCs of large preovulatory and postovulatory follicles and absent from primordial follicles. Using pharmacological activators and inhibitors, we demonstrated that LUM induction by luteinizing hormone (LH)/hCG is carried through the mitogen-activated protein kinase (MEK) pathway. LUM expression was induced in high-density cell cultures in a confluence-dependent manner. MGCs from follicles of subjects with endometriosis exhibited reduced mRNA transcription levels compared to control subjects. Our study confirms that LUM is a newly discovered ovulatory gene. LUM might play an important role during the preovulatory period up until ovulation as well as in endometriosis infertility. A better understanding of LUM’s role might provide potential new treatment paradigms for some types of female infertility

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Data Availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request

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Acknowledgements

We thank Daniela Kamir, Ph.D. (Bioforum Group), for her assistance in editing the manuscript.

Author information

Authors and Affiliations

  1. Human Reproduction Lab and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

    A Kedem, K Ulanenko-Shenkar, Y Yung, GM Yerushalmi & A Hourvitz

  2. IVF Unit, Department of Obstetrics & Gynecology, Shamir Medical Center, Zerifin, Israel

    A Kedem, M Youngster, S Avraham, GM Yerushalmi & A Hourvitz

  3. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    A Kedem, K Ulanenko-Shenkar, Y Yung, M Youngster, S Avraham, GM Yerushalmi & A Hourvitz

Authors
  1. A Kedem
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  2. K Ulanenko-Shenkar
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  3. Y Yung
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  4. M Youngster
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  5. S Avraham
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  6. GM Yerushalmi
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  7. A Hourvitz
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Contributions

AK: analyzing and interpretation of the data, major contributor in writing the manuscript

USK: lab work, analyzing and interpretation of the data, contributor in writing the manuscript

YY: study design, lab work, data analyzing and interpretation, contributor in writing the manuscript

GY: data analyzing and interpretation, contributor in writing the manuscript

MY: data analyzing and interpretation

SA: data analyzing and interpretation

HA: conception and design, interpretation, contributor in writing the manuscript

Corresponding author

Correspondence to A Kedem.

Ethics declarations

Ethics Approval and Consent to Participate

The study was approved by the local Institutional Review Board (IRB) committee of Chaim Sheba Medical Center, Tel Hashomer (ethical approval number SMC-17-4521). Written informed consent was obtained from each patient who provided samples. All experiments involving mice were conducted in compliance with the principles of the National Research Council (NRC) and were approved by the institutional animal care and use committee (IACUC) #919/14/ANIM.

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Not applicable

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The authors declare no competing interests.

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Kedem, A., Ulanenko-Shenkar, K., Yung, Y. et al. The Involvement of Lumican in Human Ovulatory Processes. Reprod. Sci. 29, 366–373 (2022). https://doi.org/10.1007/s43032-021-00650-y

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  • DOI: https://doi.org/10.1007/s43032-021-00650-y

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