Endocrine Disrupting Chemicals Interfere With Leydig Cell Hormone Pathways During Testicular Descent in Idiopathic Cryptorchidism

Fénichel, Patrick; Chevalier, Nicolas; Lahlou, Najiba; Coquillard, Patrick; Wagner-Mahler, Kathy; Pugeat, Michel; Panaïa‐Ferrari, Patricia; Brucker‐Davis, Françoise

doi:10.3389/fendo.2018.00786

Cited by 13 publications

(10 citation statements)

References 71 publications

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“…46,47 Endocrine disrupters with both estrogenic and antiandrogenic effects can interfere with the signaling and hormonal function of Leydig cells during testicular descent. [47][48][49] Thus, we suggest that exposure to glyphosate during gestation and lactation can interfere in the production/action or suppression of hormones produced by Leydig cells during the process, leading to the delayed testicular descent observed in GBH-F1 mice. In addition to these data, we found that GBH-F1 mice at PND150 exhibited lower spermatozoa number in the cauda epididymis.…”

Section: Discussionmentioning

confidence: 99%

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring

Teleken

Gomes

Marmentini

et al. 2019

J Dev Orig Health Dis

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One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother’s treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus–pituitary–testicular axis regulation in F1 offspring.

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Section: Discussionmentioning

confidence: 99%

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring

Teleken

Gomes

Marmentini

et al. 2019

J Dev Orig Health Dis

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“…Epidemiological studies together with laboratory cryptorchidism models have shown a strong link between testis descent impairment and xenoestrogen exposure. Such exposure is also associated with increased estrogen levels and expression of ER in the undescended testes [22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

Witkowski

Pardyak

Pawlicki

et al. 2021

IJMS

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Cryptorchidism in horses is a commonly occurring malformation. The molecular basis of this pathology is not fully known. In addition, the origins of high intratesticular estrogen levels in horses remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor (GPER) and establish histological and biochemical cryptorchid testis status, healthy and cryptorchid horse testes were subjected to scanning electron microscopy analysis, histochemical staining for total protein (with naphthol blue black; NBB), acid content (with toluidine blue O; TBO), and polysaccharide content (with periodic acid–Schiff; PAS). The expression of GPER was analyzed by immunohistochemistry and Western blot. GPER-mediated intracellular cAMP and calcium (Ca2+) signaling were measured immunoenzymatically or colorimetrically. Our data revealed changes in the distribution of polysaccharide content but not the protein and acid content in the cryptorchid testis. Polysaccharides seemed to be partially translocated from the interstitial compartment to the seminiferous tubule compartment. Moreover, the markedly decreased expression of GPER and GPER downstream molecules, cAMP and Ca2+, suggests their potential role in testis pathology. Increased estrogen levels in cryptorchid conditions may be linked to disturbed GPER signaling. We postulate that GPER is a prominent key player in testis development and function and may be used as a new biomarker of horse testis in health and disease.

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“…An experiment on mice showed that BPA increased germ cell apoptosis (54). On the other hand, Fenichel et al did not find a significant increase in bisphenol A in cryptorchid children (55,56). However, mean levels of bisphenol A were higher in nonpalpable compared to palpable gonads.…”

Section: Influence On Cryptorchidismmentioning

confidence: 96%

Identification of the Bisphenol A (BPA) and the Two Analogues BPS and BPF in Cryptorchidism

et al. 2021

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Objectiveto explore the association of plasma concentrations of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) with unilateral cryptorchidism. In addition, to analyze selected demographic and intraoperative characteristics.DesignRetrospective analysis to determine plasma concentrations of total BPA, BPS and BPF using gas chromatography - mass spectrometry (GC-MS) among prepubertal boys with cryptorchidism and prebupertal male control subjects. During operation, the size, turgor and location of the cryptorchid testes were assessed.Main Outcome MeasurePlasma concentrations of total BPA, BPS and BPF.ResultsIn children with cryptorchidism, plasma levels of BPA, BPS and BPF were significantly higher compared to the control subjects. For BPA, it was: median value: 9.95 ng/mL vs. 5.54 ng/mL, p<0.05. For BPS, it was: median value: 3.93 ng/mL vs. 1.45 ng/mL, p<0.001. For BPF, it was: median value: 3.56 ng/mL vs. 1.83 ng/mL, p<0.05. In cryptorchid group, BPA was detected in 61.4% samples, BPS in 19.3% and BPF in 19.3%. All the three bisphenols were detected in plasma samples of both the healthy subjects and the study cohort. In the latter group, we found significant higher levels of BPA in boys from urban areas. We found a weak positive correlation between the levels of BPS and BPF and reduced turgor of the testes. Furthermore, results showed weak positive correlations between BPA and BPS levels and the age of the children as well as between BPS and BPF concentrations and the place of residence.ConclusionsResults provide a first characterization of prepubertal boys suffering from cryptorchidism and exposed to different kind of bisphenols. Our study suggests that cryptorchid boys are widely exposed to BPA and, to a lesser extent, also to its alternatives, such as BPS and BPF.

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Endocrine Disrupting Chemicals Interfere With Leydig Cell Hormone Pathways During Testicular Descent in Idiopathic Cryptorchidism

Cited by 13 publications

References 71 publications

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring

The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

Identification of the Bisphenol A (BPA) and the Two Analogues BPS and BPF in Cryptorchidism

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