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     Martine-Culty    

Martine Culty, Ph.D. 

Associate Professor

McGill University (Research Institute of the MUHC)

Department of Medicine (primary), Pharmacology & Therapeutics (associate member)

1001 Decarie Blvd, Bloc E, #EM1-3218

Montreal, QC, H4A 3J1

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Telephone: 514-934-1934 x 43752

 

Research Interest: 

  • Male reproduction
  • Germ cell development
  • Effects of endocrine disruptors on testis development and function

 

Summary of Results

 

Our laboratory studies the physiological regulation and impact of endocrine disruptors (EDs) of testis functions and male germ cell development, focusing on the development of gonocytes, precursor cells of spermatogonia stem cells. Disturbance of this process may lead to infertility or testicular tumors.

We have established that PDGF and estradiol work in concert to stimulate neonatal rat gonocyte proliferation via ERK1/2 stimulation, while retinoic acid (RA) induces gonocyte differentiation. We showed that the ubiquitin proteasome system (UPS) participates to RA-induced differentiation of gonocytes (Manku et al BOR 2012). We recently found that RA crosstalks with PDGFRs, SRC and JAK/STAT pathways and that RA induces the expression of variant PDGFRa in gonocyte and F9 embryonal carcinoma cells (Manku et al. Endocrinology 2015). We identified pro-and anti-apoptotic genes/proteins expressed in differentiating gonocytes and seminomas (AJA 2015). Gene/protein expression studies on gonocytes and human testicular tumors identified novel candidates genes potentially involved in gonocyte development and dysregulated in testicular cancer (Manku et al. under revision).

Following earlier studies showing transient deleterious effects of estrogenic compounds on testicular cells, and short and long term negative effects of fetal exposure to high doses of the phthalate DEHP in rat testis, we recently examined the effects of fetal exposure to combinations of the phytoestrogen genistein and DEHP at doses relevant to human exposure. These studies showed changes unique to the combined EDs, affecting the expression of genes/proteins in different testicular cell types, indicating that a combination of low doses EDs induces alterations in testis different from those induced by isolated EDs (Jones et al. BOR 2014). The study of short term effects showed alterations on testicular cells different from the long term effects, and revealed the involvement of anti-oxidant response genes to DEHP exposure that was normalized by combination with genistein (Jones et al. submitted).

We also have long term collaboration with the team of Vassilios Papadopoulos on the regulation of steroid synthesis and the impact of DEHP on this process, which had led to several recent articles.

 

Laboratory members: 

Name

Position

Email Address

Annie Boisvert

Technician

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Gurpreet Manku

Postdoc fellow (RI-MUHC)

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Steve Jones

PhD student, EXMD

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Chi Chon Kong

MSc student, EXMD

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Andrada Naghi

Undergrad Pharm (summer)

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 Gurpreet-Annie

Steve-Gurpreet-Annie

Tam-Annie

List of Publications:

(selected from 2010-present)

Manku G, Wang Y, Merkbaoui V, Boisvert A, Ye X , Blonder J, Culty M 2015 Role of Retinoic Acid and Platelet-Derived Growth Factor Receptor crosstalk in the regulation of neonatal gonocyte and embryonal carcinoma cell differentiation. Endocrinology, 1(1):346-359.

Manku G, Culty M 2015 Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas. Asian J. Androl., 17:403-414.

Manku G, Culty M 2015 Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges Reproduction, 149(3):R139-157.

Culty M, Liu Y, Manku G, Chan W-Y, Papadopoulos V Expression of steroidogenesis-related genes in murine male germ cells. Under revision at Steroids.

Jones S, Boisvert A, Francois S, Zhang L, Culty M Testicular effects of Di-(2-ethylhexyl) Phthalate are antagonized by genistein in young rats exposed in utero. Submitted to BOR

Jones S, Boisvert A, Duong T, Francois S, Thrane P, Culty M 2014 Disruption of Rat Testis Development Following Combined In-Utero Exposure to the Phytoestrogen Genistein and Anti-Androgenic Plasticizer Di-(2-Ethylhexyl) Phthalate. Biology of Reproduction, 91(3):64

Aghazadeh Y, Martinez-Arguelles DB, Fan J, Culty M, Papadopoulos V 2014 Induction of Androgen Formation in the Male by a TAT-VDAC1 Fusion Peptide Blocking 14-3-3ɛ Protein Adaptor and Mitochondrial VDAC1 Interactions. Mol Ther. 22(10):1779-91

Bose R, Manku G, Culty M, Wing SS. 2014 Ubiquitin-proteasome system in spermatogenesis. Adv Exp Med Biol;759:181-213

Culty M 2013 Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name? Biology of Reproduction. 89:46, 1-6.

Martinez-Arguelles DB, Campioli E, Lienhart C, Fan J, Culty M, Zirkin BR, Papadopoulos V 2014 In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate induces long-term changes in gene expression in the adult male adrenal gland. Endocrinology; 155:1667-78.

Manku G, Wing SS, Culty M 2012 Expression of the Ubiquitin Proteasome System in Neonatal Rat Gonocytes and Spermatogonia: Role in Gonocyte Differentiation. Biology of Reproduction, 87:44, 1-18.

Manku G, Mazer M and Culty M 2012 Neonatal testicular gonocytes isolation and processing for immunocytochemical analysis. Methods in Mol. Biol., 825:17-29.

Wang Y and Culty M 2012 Preparation of enriched mouse syncitia-free pachytene spermatocyte cell suspensions. Methods in Molecular Biology, 825: 67-74.

Manku G, Wang Y, Thuillier R, Rhodes C, Culty M 2011 Developmental expression of TSPO in testicular germ cells. Current Molecular Medicine, 12:467-475.

Martinez-Arguelles DB, Guichard T, Culty M, Zirkin BR, Papadopoulos V 2011 In Utero Exposure to the Antiandrogen Di-(2-Ethylhexyl) Phthalate Decreases Adrenal Aldosterone Production in the Adult Rat. Biology of Reproduction, 85:51-61.

Thuillier R, Mazer M, Manku G, Boisvert A, Wang Y, Culty M 2010 Interdependence of PDGF and estrogen signaling pathways in inducing neonatal rat testicular gonocytes proliferation. Biology of Reproduction, 82:825-836.

 

Awards:

To M. Culty: Conference Speaker Award, 18th World Congress on Advances in Oncology, Crete, Greece (2013)

To Gurpreet Manku (PhD, Postdoc): From 2010 to 2015, Gurpreet has obtained Scholarships and travel awards from regional and international organizations, including the Society for the Study of Reproduction, the RIKEN (Japan), the Réseau Québécois en Reproduction (RQR); the Center for the Study of Reproduction (CSR) at McGill University, the Department of Pharmacology at McGill University, the Division of Endocrinology at the RI-MUHC and Principal’s Graduate Fellowship Awards from McGill University. She has also obtained several awards for oral and poster presentations at meetings.

To S Jones (PhD student): From 2013 to 2015, Steve has obtained a NSERC Scholarship, academic and travel awards from regional and international organizations, including the Society for the Study of Reproduction, the RIKEN (Japan), the Réseau Québécois en Reproduction (RQR); the Center for the Study of Reproduction (CSR) at McGill University, the division of Experimental Medicine at McGill University, the Division of Endocrinology at the RI-MUHC, the Society of Toxicology and the American Society of Andrology.