Eicosanoid Biosynthesis in Male Reproductive Development: Effects of Perinatal Exposure to NSAIDs and Analgesic Drugs

Abstract

Increasing rates of infertility associated with declining sperm counts and quality, as well as increasing rates of testicular cancer are contemporary issues in the United States and abroad. These conditions are part of the Testicular Dysgenesis Syndrome, which includes a variety of male reproductive disorders hypothesized to share a common origin based on disrupted testicular development during fetal and neonatal stages of life. Male reproductive development is a highly regulated and complex process that relies on an intricate coordination between germ, Leydig, and Sertoli cells as well as other supporting cell types, to ensure proper spermatogenesis, testicular immune privilege, and endocrine function. The eicosanoid system has been reported to be involved in the regulation of fetal and neonatal germ cell development as well as overall testicular homeostasis. Moreover, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics with abilities to block eicosanoid synthesis by targeting either or both isoforms of cyclooxygenase enzymes, have been found to adversely affect male reproductive development. This review will explore the current body of knowledge on the involvement of the eicosanoid system in male reproductive development, as well as discuss adverse effects of NSAIDs and analgesic drugs administered perinatally, focusing on toxicities reported in the testis and on major testicular cell types. Rodent and epidemiological studies will be corroborated by findings in invertebrate models for a comprehensive report of the state of the field, and to add to our understanding of the potential long-term effects of NSAID and analgesic drug administration in infants.

Fetal Exposure to Endocrine Disrupting-Bisphenol A (BPA) Alters Testicular Fatty Acid Metabolism in the Adult Offspring: Relevance to Sperm Maturation and Quality

“…Decreased levels of n-6 LCPUFA may affect spermatogenesis by reducing prostaglandin (PG) production. The cyclooxygenase (COX) enzyme regulates gonadal development via PG in the testis [ 15 ]. ARA, liberated from phospholipids, is rapidly converted to PGs by COX enzymes and thus stimulates testicular steroidogenesis during spermatogenesis.…”

“…Eicosanoid biosynthesis involves testicular development by supporting PG synthesis, which is needed for germ cell development and steroidogenesis. Arachidonic acid, 20:4 n-6 (ARA), is a precursor for the PG-2 series during testicular steroidogenesis in spermatogenesis [ 15 ]. Although the involvement of PGs is well-established in female reproduction, their role in male fertility was later evidenced by dysregulated cyclooxygenase-2 (COX2) expression in infertile subjects [ 16 ].…”

Fetal exposure to endocrine disrupting-bisphenol A (BPA) alters testicular fatty acid metabolism in the adult offspring: relevance to sperm maturation and quality

“…Decreased levels of n-6 LCPUFA may affect spermatogenesis by reducing prostaglandin (PG) production. The cyclooxygenase (COX) enzyme regulates gonadal development via PG in the testis (Tran-Guzman and Culty 2022). ARA, liberated from phospholipids, is rapidly converted to PGs by COX enzymes and thus stimulates testicular steroidogenesis during spermatogenesis.…”

“…Eicosanoid biosynthesis involves testicular development by supporting PG synthesis, which is needed for germ cell development and steroidogenesis. Arachidonic acid, 20:4 n-6 (ARA), is a precursor for PG-2 series during testicular steroidogenesis in spermatogenesis [15].…”

“…Eicosanoid biosynthesis involves testicular development by supporting PG synthesis, which is needed for germ cell development and steroidogenesis. Arachidonic acid, 20:4 n-6 (ARA), is a precursor for PG-2 series during testicular steroidogenesis in spermatogenesis (Tran-Guzman and Culty 2022). Although the involvement of PGs is well established in female reproduction, their role in male fertility was later evidenced by dysregulated cyclooxygenase-2 (COX2) expression in infertile subjects (Matzkin et al 2010).…”