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Hugh Clarke, Ph.D.

Associate Professor

McGill University

Department of Obstetrics and Gynecology

Royal Victoria Hospital

1001, Décarie Blvd, room F3.50

Montreal, Qc

H4A 3J1

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Telephone: 514 934-1934 ext. 34748

Fax: 514 843-1662 

 

Field of research:

  • Oocyte growth and development;
  • Ccommunication between the germ cell and its somatic niche.

Resume of recent results:

1. It has long been known that ovulation is triggered by a surge of luteinizing hormone (LH). Recent studies have revealed that LH acts by triggering the mural granulosa cells of antral follicles to release epidermal growth factor (EGF)-like peptides, which bind to EGF receptors (EGFR) on the granulosa cells and initiate the multiple events of ovulation. We have discovered that follicle-stimulating hormone (FSH) is required to increase the expression of EGFR on the granulosa so that EGF can trigger a biological response. These results identify a new essential function for FSH in the signaling cascade that regulates ovulation and reinforce the concept that FSH and LH act cooperatively in this process

2. Development of the germ cells requires continuous interaction with its somatic microenvironment or niche, which is essential for fertility. Little is known, however, of the signals that modulate these interactions. We have found that FSH increases gap junctional communication between growing oocytes and the granulosa cells that surround them. FSH also increases the expression of the connexin proteins that make up these gap junctions as well as cadherins that mediate cell adhesion. These results indicate that FSH enhances female fertility in part by increasing contact and communication between the developing oocyte and its environment.

 

     3. The technique of oocyte maturation in vitro (IVM) is employed clinically in some cases of unexplained fertility or when there is a risk of potentially lethal ovarian hyperstimulation. However, in vitro-matured oocytes develop relatively poorly as embryos, limiting the value of this technique. We have found that the widespread and extensive degradation of mRNA that occurs during maturation in vivo is impaired during IVM. This impaired degradation is not rescued by the presence of the cumulus cells or of EGF. We speculate that resulting excess maternal mRNA in fertilized eggs may compete for access to the translational machinery and thus impede embryonic development. Understanding why degradation is impaired will proved a basis for modifications to IVM culture media so that the normal regulation and dynamics are restored.

 

Laboratory members: 

Name

Position

Email Address

Qin YANG

Research Assistant

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Stephany EL-HAYEK

PhD student

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Omar (Karl) VIEUX

PhD student

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Laleh ABBASSI

MSc student

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Maria Eyzaguirre

MSc student

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Suhaib Khayat

MSc student

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 Selected publications: 

Demeestere, I., A, Streiff, J. Suzuki, S. Al-Khabouri, E. Mahrous, S. L. Tan and H. J. Clarke. (2012). Follicle-stimulating hormone accelerates mouse oocyte development in vivo. Biol. Reprod. 87, 3, 1-11.

Bedard, N., Y. Yang, M. Gregory, D. G. Cyr, J. Suzuki, X. Yu, R.-C. Chian, L. Hermo, C. O’Flaherty, C. E. Smith, H. J. Clarke and S. S. Wing (2011). Mice lacking the USP2 deubiquitinating enzyme have severe male sub-fertility associated with defects in fertilization and sperm motility. Biol. Reprod. 85, 594-604.

Elizur, S.E., W. Y. Son, H. Clarke, D. Morris, Y. Gidoni, E. Demirtas and S. L. Tan (2011). A unique biological in-vivo model to evaluate follicular development during in-vitro maturation treatment. Reprod. Biomed. Online 22, 257-262.

Yang, Q., P. Allard, M. Huang, W-L. Zhang and H. J. Clarke (2010). Proteasomal activity is required to initiate and to sustain translational activation of messenger RNA encoding the stem-loop-binding protein during meiotic maturation in mice. Biol. Reprod. 82, 123-131.

 

Awards:

Richard Cruess Chair in Reproductive Biology (McGill)