Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes

Singh, Shilpi

doi:10.1002/jat.3883

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…The slides were then washed, mounted with anti-fed mounting media (DABCO:1, 4-diazabicyclo- 2.2.2-octane), and examined under fluorescence microscope (Leica DM3000, Germany). Immunopositive signals were presented as mean fluorescence intensity after analyzing the image in Image J software [35].…”

Section: Methodsmentioning

confidence: 99%

Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats

Yadav

Mishra

2022

Neuroendocrinology

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Introduction: Male sexual potency and vigor are a complex neuroendocrine process and an important component of well-being. Psychological stress is one of the leading causes of male impotence worldwide. Therefore, to better understand the effects of psychological stress on male sexual potency, vigor, and the physiology of erection, we used the rat restraint stress (RS) model, which can most aptly simulate psychological stress. Methods: Adult male SD rats were exposed to RS for 1.5 or 3 hours/day for 30 days. Neuromodulators and hormones of sexual potency and penile erection were quantified using ELISA kit. The histoarchitecture of the penis was examined using Masson trichrome staining. Immunoblotting and immunofluorescence were used to assess the expression and immunolocalization patterns of penile erection markers. To assess sexual potency and vigor, a non-contact erection and a copulatory test were performed. Results: RS exposure decreased the circulatory levels of gonadotropins and testosterone while increasing the serum corticosterone level. RS exposure altered the histomorphology of the penis by decreasing the smooth muscle/collagen ratio and increasing oxidative stress in penile tissue. Furthermore, RS adversely affected NO availability for penile erection by decreasing the neurotransmitter acetylcholine and other erection facilitatory markers such as p-Akt, nNOS, eNOS, and cGMP, while increasing the inhibitory marker PDE5α in the penis. RS exposure significantly reduced the frequencies of mount, intromission and ejaculation, whereas it prolonged sexual exhaustion by increasing latencies of postejaculatory mount, intromission, and ejaculation. Conclusion: The current findings suggest that psychological stressors, such as restraint stress, cause erectile dysfunction in adult male rats by modulating the hypothalamic-pituitary-testicular axis, oxidative balance, penile fibrosis, and the NO/cGMP/PDE5α pathway of penile erection.

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Section: Methodsmentioning

confidence: 99%

Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats

Yadav

Mishra

2022

Neuroendocrinology

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“…Singh and Singh (2019a) exposed Parkes mice orally to PFNA (0, 2 and 5 mg/kg bw per day, 10 dams per group) from GD 12 to parturition, and testes of two male pups per dam were investigated on PND 3. In dams, the body weight was not affected, and there were no changes in birth rate, number of pups per dam and weight of male pups.…”

Section: Assessmentmentioning

confidence: 99%

“…In females, testosterone was dose-relatedly and significantly increased (66% increase at highest dose) but vaginal cytological data indicated cyclicity similar to controls. Singh and Singh (2019a) exposed Parkes mice orally to PFNA (0, 2 and 5 mg/kg bw per day, 10 dams per group) from GD 12 to parturition, and testes of two male pups per dam were investigated on PND 3. In dams, the body weight was not affected, and there were no changes in birth rate, number of pups per dam and weight of male pups.…”

Section: Pfcasmentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

304

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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“…In one experiment, exposure of pregnant rats to 1 to 500 mg HFPO-DA/kg/ day during male reproductive development (GD14-18) did not result in changes in in vitro receptor activity, testosterone production, or expression of key genes involved in male reproductive development in the fetal testis but reduced male reproductive tissue weights (Conley et al 2019). Exposure to another PFAS, perfluorononanoic acid (PFNA) during gestation caused alterations in Leydig and Sertoli cell function that were detectable in neonatal testis as decreased expression of SF-1, Leydig cell markers (STAR, CYP17, HSD3B, and HSD17B), and Sertoli cell markers (WT1 and AMH) (Singh & Singh 2019). Given wide exposure to PFAS and evidence that PFAS threaten male reproductive system development, future studies will be needed to clarify the PFAS mode of action on the male reproductive axis, including more studies of emerging PFAS chemicals, using physiologically relevant exposure routes and concentration levels.…”

Section: Fetal Testis Development: Toxicity Mechanisms F157mentioning

confidence: 99%

REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond

Spade

2021

Reproduction

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Fetal development of the mammalian testis relies on a series of interrelated cellular processes: commitment of somatic progenitor cells to Sertoli and Leydig cell fate, migration of endothelial cells and Sertoli cells, differentiation of germ cells, deposition of basement membrane, and establishment of cell-cell contacts, including Sertoli-Sertoli and Sertoli-germ cell contacts. These processes are orchestrated by intracellular, endocrine, and paracrine signaling processes. Because of this complexity, testis development can be disrupted by a variety of environmental toxicants. Toxicity of phthalic acid esters (phthalates) to the fetal testis has been the subject of extensive research for two decades, and phthalates have become an archetypal fetal testis toxicant. Phthalates disrupt the seminiferous cord formation and maturation, Sertoli cell function, biosynthesis of testosterone in Leydig cells, and impair germ cell survival and development, producing characteristic multinucleated germ cells. However, the mechanisms responsible for these effects are not fully understood. This review describes current knowledge of the adverse effects of phthalates on the fetal testis and their associated windows of sensitivity, and compares and contrasts the mechanisms by which toxicants of current interest, bisphenol A and its replacements, analgesics, and perfluorinated alkyl substances, alter testicular developmental processes. Working towards a better understanding of the molecular mechanisms responsible for phthalate toxicity will be critical for understanding the long-term impacts of environmental chemicals and pharmaceuticals on human reproductive health.

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Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes

Cited by 9 publications

References 42 publications

Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats

Sub-Chronic Restraint Stress Suppresses Sexual Potency and Erection Efficiency by Targeting the Hypothalamic-Pituitary-Testicular Axis and the Nitric Oxide/Cyclic Guanosine Monophosphate/Phosphodiesterase 5α Pathway in Adult Rats

Risk to human health related to the presence of perfluoroalkyl substances in food

REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond

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