Can maternal exposure to paracetamol impair reproductive parameters of male rat offspring?

Pereira, Marina Rangel Ferro; Aleixo, Jeberson Fernando; Cavalcanti, Liara de Freitas; Costa, Nathalia Orlandini; Vieira, Milene Leivas; Ceravolo, Graziela Scalianti; Moreira, Estefânia Gastaldello; Gerardin, Daniela Cristina Ceccatto

doi:10.1016/j.reprotox.2019.12.007

Cited by 12 publications

(9 citation statements)

References 41 publications

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“…We also found altered endocrine pathways between control and treated offspring, which may align with prior work showing APAP interference with sexual development in rodents. Prenatal APAP exposure in rodents may cause decreased anogenital distance ( Kristensen et al, 2011 ; Holm et al, 2015 ; van Den Driesche et al, 2015 ; Holm et al, 2016 ), decreased pelvic floor muscle weights ( Axelstad et al, 2014 ), increased nipple retention ( Axelstad et al, 2014 ; Mandrup et al, 2015 ), increased testosterone ( Pereira et al, 2020 ), and decreased male and female fertility ( Dean et al, 2016 ; Johansson et al, 2016 ; Axelstad et al, 2018 ; Rossitto et al, 2019a ; Rossitto et al, 2019b ).…”

Section: Discussionmentioning

confidence: 99%

Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice

Baker¹,

Rafikian²,

Hamblin³

et al. 2023

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice

Baker¹,

Rafikian²,

Hamblin³

et al. 2023

Neurobiology of Disease

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“…Therefore, the evaluation of tubular length is necessary, given the fact that a reduction in the length and diameter of the tubules may cause atrophic changes and a decrease in tubular volume (Noorafshan et al, 2011). From a recent study emerged how the proliferation of Sertoli cells and spermatogenic cells occurring during puberty increases the diameter and length of the seminiferous tubules leading subsequently to an increase in testicular volume (Pereira et al, 2020). Therefore, the decrease in diameter and length of seminiferous tubules occurring in most 30-day old groups and in all 60-day old ones is presumed to be the result of the cessation of the above-mentioned cellular proliferation process.…”

Section: Discussionmentioning

confidence: 99%

Study on the effect of maternal administration of oxaliplatin on offspring testes using unbiased design-based stereology

Sadeghinezhad¹,

Dahmardeh²,

Tootian³

et al. 2021

J Exp Clin Med

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Oxaliplatin (Ox) is widely used for the treatment of various tumors. Since Ox prevents DNA replication and transcription, it may affect organs with rapid cell divisions such as the testes. Although its use during pregnancy has been reported, no information regarding its effects on the testes of the offspring is not available yet. Thirty-two mice were randomly divided into four groups. The control group (1) was administered intraperitoneally 0.2 ml of saline three times a week for the 21 days of pre-pregnancy, pregnancy and lactation. Experimental groups 2, 3 and 4 received 3 mg/kg of oxaliplatin three times a week for 21 days during pre-pregnancy, pregnancy and lactation, respectively. The left testis was removed from male offspring 30 and 60 days after birth. The volume of the testes, seminiferous tubules and interstitial tissue, the surface area and height of the seminiferous epithelium, as well as the length and diameter of seminiferous tubules, were analyzed by means of stereology. Results showed a decrease in the evaluated parameters in experimental groups, in comparison with the control group. Due to the ameliorating effect of Ox on offspring testes, cautiousness is needed during maternal administration in order to preserve the fertility of male offspring.

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“…Exposure of female rats to APAP (350 mg/kg/day during gestation and lactation) did not affect the AGD and preputial separation (at 21 dpp) and testosterone production and sperm parameters (in adulthood) in their male offspring. However, sexual behavior (first and number of ejaculations) was significantly reduced in the exposed male offspring, suggesting impaired sexual hypothalamic differentiation ( Pereira et al, 2020 ). These effects on puberty onset and sexual behavior and the differential effects between ex vivo and in vivo studies, might be the consequences of the central effects of IBU and APAP, in addition to their peripheral effects.…”

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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Can maternal exposure to paracetamol impair reproductive parameters of male rat offspring?

Cited by 12 publications

References 41 publications

Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice

Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice

Study on the effect of maternal administration of oxaliplatin on offspring testes using unbiased design-based stereology

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

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