Pre-pubertal exposure to ibuprofen impairs sperm parameters in male adult rats and compromises the next generation

Barbosa, Mariana Gazoli; Jorge, Bárbara Campos; Stein, Júlia; Ferreira, Dayana Agnes Santos; Barreto, Ana Carolina da Silva; Reis, Ana Carolina Casali; Moreira, Suyane da Silva; Inocêncio, Leonardo Cesar de Lima; Macorini, Luís Fernando Benitez; Arena, Arielle Cristina

doi:10.1080/15287394.2020.1786483

Cited by 15 publications

(15 citation statements)

References 52 publications

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“…Daily sperm production was significantly decreased when rats were exposed to the highest dose of ibuprofen (14.3 mg/kg), but sperm transit time or morphology was not affected by the treatment. Furthermore, fertility was also reduced in highest dose group, including greater pre-implantation loss rates of the offspring ( Barbosa et al, 2020 ).…”

Section: Eicosanoid System In Male Reproductive Developmentmentioning

confidence: 99%

“…Other studies did not observe such an effect on the AGDi of rat offspring exposed in utero to these drugs, which may suggest an ability of the testes to recover by birth and subsequently, resume normal reproductive potential in puberty and adulthood ( Dean et al, 2013 ; Axelstad et al, 2014 ). While fetal exposure of ibuprofen did not have long-term effects on sperm motility or viability ( Stutz and Munoz 2000 ), pre-pubertal exposure did lead to decreased sperm production and fertility ( Barbosa et al, 2020 ). However, no report has evaluated the immediate and long-term effects of neonatal exposure of NSAIDs, which is of interest to us due the significant plasticity of the testes during this stage of development.…”

Section: Eicosanoid System In Male Reproductive Developmentmentioning

confidence: 99%

“…In rats exposed to ibuprofen during juvenile and peripubertal stages of development, 2.4 and 7.2 mg/kg/day doses resulted in reduced testosterone levels, while the 7.2 mg/kg/day dose presented increased FSH and altered LH levels. Furthermore, all treatment groups exhibited decreased Leydig cell number and significantly reduced Leydig cell volume in the 2.4 mg/kg/day treatment group ( Barbosa et al, 2020 ). In human adult testis explants exposed to 10 –4 M aspirin, 10 –5 M indomethacin, and 10 –5 M and 10 –4 M acetaminophen, testosterone secretion was decreased, while INSL3 expression was reduced by both aspirin concentrations and 10 –4 M indomethacin after 24 h, but the number of Leydig cells was increased by 10 –4 M aspirin and 10 –5 M indomethacin.…”

Section: Eicosanoid System In Male Reproductive Developmentmentioning

confidence: 99%

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

Tran-Guzman

Culty

2022

Front. Toxicol.

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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.

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Section: Eicosanoid System In Male Reproductive Developmentmentioning

confidence: 99%

Section: Eicosanoid System In Male Reproductive Developmentmentioning

confidence: 99%

Section: Eicosanoid System In Male Reproductive Developmentmentioning

confidence: 99%

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

Tran-Guzman

Culty

2022

Front. Toxicol.

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“…IBU treatment reduced testosterone secretion and altered the sperm quantity and quality: decreased sperm motility and daily sperm production. In the progeny of the exposed animals, sperm transit time in the epididymis was accelerated in males, and estrous cycle was altered and fertility potential reduced in females ( Barbosa et al, 2020 ). Moreover, in adult rats, long-term treatment with APAP at high doses (500–1,000 mg/kg for 30 days) impaired sexual competence, sperm count and quality, and fertility.…”

Section: In Vivo Experiments In Rodents To Elucidate the Imp...mentioning

confidence: 99%

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

et al. 2022

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Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (acetylsalicylic acid), diclofenac and ibuprofen (IBU), and analgesic drugs, such as acetaminophen (APAP, or paracetamol), are widely used to treat inflammation and pain. APAP and IBU are over-the-counter drugs and are among the most commonly taken drugs in the first trimester of pregnancy, even in combination. Furthermore, these drugs and their metabolites are released in the environment, and can be frequently detected in wastewater, surface water, and importantly in drinking water. Although their environmental concentrations are much lower than the therapeutics doses, this suggests an uncontrolled low-dose exposure of the general population, including pregnant women and young children, two particularly at risk populations. Epidemiological studies show that exposure to these molecules in the first and second trimester of gestation can favor genital malformations in new-born boys. To investigate the cellular, molecular and mechanistic effects of exposure to these molecules, ex vivo studies with human or rodent gonadal explants and in vivo experiments in rodents have been performed in the past years. This review recapitulates recent data obtained in rodent models after in utero or postnatal exposure to these drugs. The first part of this review discusses the mechanisms by which NSAIDs and analgesics may impair gonadal development and maturation, puberty development, sex hormone production, maturation and function of adult organs, and ultimately fertility in the exposed animals and their offspring. Like other endocrine disruptors, NSAIDs and APAP interfere with endocrine gland function and may have inter/transgenerational adverse effects. Particularly, they may target germ cells, resulting in reduced quality of male and female gametes, and decreased fertility of exposed individuals and their descendants. Then, this review discusses the effects of exposure to a single drug (APAP, aspirin, or IBU) or to combinations of drugs during early embryogenesis, and the consequences on postnatal gonadal development and adult reproductive health. Altogether, these data may increase medical and public awareness about these reproductive health concerns, particularly in women of childbearing age, pregnant women, and parents of young children.

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“…This is in line with the experimental findings that report IBPPA has no significant negative impact on DNA, 44 or the studies that show it prevents DNA damage. 45 Also, it should be noted that A nucleobases are more susceptible to mutagenic lesion formation when interacting with some carbonyl containing compounds (such as formaldehyde 46 Based on the NBO results, more accurate interaction energies were calculated only for BaP, BPDE, DMBQ and PQ by cropping the effective DNA binding sites (i.e. the main interacting nucleotides).…”

Section: Dna and Hsa Dockingmentioning

confidence: 99%

Molecular level insights into the direct health impacts of some organic aerosol components

Keshavarz

2021

New J. Chem.

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Pre-pubertal exposure to ibuprofen impairs sperm parameters in male adult rats and compromises the next generation

Cited by 15 publications

References 52 publications

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

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

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

Molecular level insights into the direct health impacts of some organic aerosol components

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