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Gestational exposure to Δ9-THC impacts ovarian follicular dynamics and angiogenesis in adulthood in Wistar rats

Published online by Cambridge University Press:  07 January 2021

Annia A. Martínez-Peña ,
Kendrick Lee ,
James J. Petrik ,
Daniel B. Hardy  and
Alison C. Holloway Open the ORCID record for Alison C. Holloway [Opens in a new window]
Annia A. Martínez-Peña
Affiliation:
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
Kendrick Lee
Affiliation:
The Children’s Health Research Institute, The Lawson Health Research Institute, Departments of Obstetrics and Gynecology and Physiology and Pharmacology, Western University, London, Ontario, Canada
James J. Petrik
Affiliation:
Department of Biomedical Sciences, University of Guelph, Guelph, Canada
Daniel B. Hardy
Affiliation:
The Children’s Health Research Institute, The Lawson Health Research Institute, Departments of Obstetrics and Gynecology and Physiology and Pharmacology, Western University, London, Ontario, Canada
Alison C. Holloway*
Affiliation:
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
*
Address for correspondence: Dr. Alison Holloway, Department of Obstetrics and Gynecology, McMaster University, Hamilton, ONL8N 3Z5, Canada. Email: hollow@mcmaster.ca
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Abstract

With the legalization of marijuana (Cannabis sativa) and increasing use during pregnancy, it is important to understand its impact on exposed offspring. Specifically, the effects of Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, on fetal ovarian development and long-term reproductive health are not fully understood. The aim of this study was to assess the effect of prenatal exposure to Δ9-THC on ovarian health in adult rat offspring. At 6 months of age, Δ9-THC-exposed offspring had accelerated folliculogenesis with apparent follicular development arrest, but no persistent effects on circulating steroid levels. Ovaries from Δ9-THC-exposed offspring had reduced blood vessel density in association with decreased expression of the pro-angiogenic factor VEGF and its receptor VEGFR-2, as well as an increase in the anti-angiogenic factor thrombospondin 1 (TSP-1). Collectively, these data suggest that exposure to Δ9-THC during pregnancy alters follicular dynamics during postnatal life, which may have long-lasting detrimental effects on female reproductive health.

Keywords

Δ9-THCdevelopmental toxicologyreproductive healthovarian functionfollicular angiogenesis
Type
Brief Reports
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 6 , December 2021 , pp. 865 - 869
Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

World Health Organization (WHO). The Health and Social Effects of Nonmedical Cannabis Use. At https://www.who.int/substance_abuse/publications/cannabis_report/en/ Google Scholar
Singh, S, Filion, KB, Abenhaim, HA, Eisenberg, MJ. Prevalence and outcomes of prenatal recreational cannabis use in high-income countries: a scoping review. BJOG. 2020; 127, 8–16.CrossRefGoogle ScholarPubMed
Carlier, J, Huestis, MA, Zaami, S, Pichini, S, Busardò, FP. Monitoring perinatal exposure to cannabis and synthetic cannabinoids. Ther Drug Monit. 2020; 42, 194–204.Google Scholar
Brents, LK. Marijuana, the endocannabinoid system and the female reproductive system. Yale J Biol Med. 2016; 89, 175–191.Google ScholarPubMed
Allais, A, Albert, O, Lefèvre, PLC, et al. In utero and lactational exposure to flame retardants disrupts rat ovarian follicular development and advances puberty. Toxicol Sci. 2020; 175, 197–209.CrossRefGoogle ScholarPubMed
Buckley, NE, Hansson, S, Harta, G, Mezey, E. Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat. Neuroscience. 1998; 82, 1131–1149.CrossRefGoogle ScholarPubMed
Biegon, A, Kerman, IA. Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain. Neuroimage. 2001; 14, 1463–1468.CrossRefGoogle ScholarPubMed
De Domenico, E, Todaro, F, Rossi, G, et al. Overactive type 2 cannabinoid receptor induces meiosis in fetal gonads and impairs ovarian reserve. Cell Death Dis. 2017; 8, e3085.Google Scholar
Natale, BV, Gustin, KN, Lee, K et al. Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta. Sci Rep. 2020; 10, 544.CrossRefGoogle ScholarPubMed
Pampanini, V, Jahnukainen, K, Sahlin, L, et al. Impact of uteroplacental insufficiency on ovarian follicular pool in the rat. Reprod Biol Endocrinol. 2019; 17, 10.CrossRefGoogle ScholarPubMed
De Bruin, JP, Dorland, M, Bruinse, HW, et al. Fetal growth retardation as a cause of impaired ovarian development. Early Hum Dev. 1998; 51, 39–46.CrossRefGoogle ScholarPubMed
Klein, C, Karanges, E, Spiro, A, et al. Cannabidiol potentiates Delta(9)-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology (Berl). 2011; 218, 443–457.CrossRefGoogle ScholarPubMed
Schwope, DM, Karschner, EL, Gorelick, DA, Huestis, MA. Identification of recent cannabis use: Whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration. Clin Chem. 2011; 57, 1406–14.CrossRefGoogle ScholarPubMed
Falcon, M, Pichini, S, Joya, J, et al. Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: comparison with testing in placental and fetal remains. Forensic Sci Int. 2012; 218, 92–96.CrossRefGoogle ScholarPubMed
Tsoulis, MW, Chang, PE, Moore, CJ, et al. Maternal high-fat diet-induced loss of fetal oocytes is associated with compromised follicle growth in adult rat offspring. Biol Reprod. 2016; 94, 94.CrossRefGoogle ScholarPubMed
Steiner, AZ, D’Aloisio, AA, DeRoo, LA, Sandler, DP, Baird, DD. Association of intrauterine and early-life exposures with age at menopause in the Sister study. Am J Epidemiol. 2010; 172, 140–148.CrossRefGoogle ScholarPubMed
Gougeon, A, Chainy, GB. Morphometric studies of small follicles in ovaries of women at different ages. J Reprod Fertil. 1987; 81, 433–442.CrossRefGoogle ScholarPubMed
Nelson, LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009; 360, 606–614.CrossRefGoogle ScholarPubMed
Robinson, RS, Woad, KJ, Hammond, AJ, et al. Angiogenesis and vascular function in the ovary. Reproduction. 2009; 138, 869–881.CrossRefGoogle ScholarPubMed
Chang, X, Li, H, Li, Y, et al. RhoA/MLC signaling pathway is involved in Δ9-tetrahydrocannabinol-impaired placental angiogenesis. Toxicol Lett. 2018; 285, 148–155.CrossRefGoogle ScholarPubMed
Chan, KA, Bernal, AB, Vickers, MH, et al. Early life exposure to undernutrition induces ER stress, apoptosis, and reduced vascularization in ovaries of adult rat offspring. Biol Reprod. 2015; 92, 110.CrossRefGoogle ScholarPubMed
Greenaway, J, Lawler, J, Moorehead, R, et al. Thrombospondin-1 inhibits VEGF levels in the ovary directly by binding and internalization via the low density lipoprotein receptor-related protein-1 (LRP-1). J Cell Physiol. 2007; 210, 807–818.CrossRefGoogle Scholar
Fraser, HM, Wulff, C. Angiogenesis in the primate ovary. Reprod Fertil Dev. 2001; 13, 557–566.CrossRefGoogle ScholarPubMed
Greenaway, J, Connor, K, Pedersen, HG, et al. Vascular endothelial growth factor and its receptor, Flk-1/KDR, are cytoprotective in the extravascular compartment of the ovarian follicle. Endocrinology. 2004; 145, 2896–2905.CrossRefGoogle ScholarPubMed