The Association of Certain Seminal Phthalate Metabolites on Spermatozoa Apoptosis: An Exploratory Mediation Analysis via Sperm Protamine

Xiong, Feng; Zhou, Bin; Wu, Nan-Xin; Xie, Jin-Ying; Li, Xiaojie; Chen, Yingjun; Wang, Yi‐Xin; Zeng, Qiang; Pan, Yang

doi:10.1016/j.envpol.2022.118969

Cited by 7 publications

(4 citation statements)

References 74 publications

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“…Some studies have suggested that, similarly to BPs, exposure to phthalates may induce sperm apoptosis. The evidence was provided that phthalate exposure in humans was linked to higher protamine levels in the spermatozoa, which may play a role in sperm apoptosis [ 90 ]. The study of Marchiani et al, showed that after in vitro incubation of human spermatozoa with phthalate, sperm’s progressive motility was dramatically reduced.…”

Section: Resultsmentioning

confidence: 99%

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality

2022

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Exposure to endocrine-disrupting chemicals (EDCs) may result in oxidative stress and endocrine system disturbance, which can have an impact on human reproduction and development. In male reproductive health, EDCs have been related to impaired reproductive function and male infertility, altered fetal development, and testicular germ-cell, prostate, and breast cancers. We conducted an electronic search using PubMed on endocrine disruptors related to oxidative stress and male infertility, and evaluated their association with endocrine-disrupting chemicals (bisphenols, phthalates, and parabens) in 25 articles. Higher levels of urinary bisphenols showed correlation with impaired semen quality and increased DNA damage. Considering phthalates and their metabolites, all studies found a positive association between urinary levels of phthalates and at least one semen parameter indicative of low semen quality; some studies also revealed sperm DNA damage. The studies on parabens less often revealed correlation of urinary parabens concentrations with a decrease in sperm count, as well as motility and DNA damage. Moreover, EDCs can elevate ROS production and lipid peroxidation, increase apoptosis, induce epigenetic modifications, and change the Y:X sperm chromosome ratio and sperm protein composition. Our review revealed detrimental effects of EDCs on semen quality and sperm DNA integrity—especially in BPA and phthalates, but also in parabens.

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Section: Resultsmentioning

confidence: 99%

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality

2022

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“…Moreover, mechanistic research suggests that sperm protamine serves as a molecular biomarker during spermatozoa apoptotic processes, potentially mediating the association between PAE exposure and spermatozoa apoptosis ( 291 ). Furthermore, lipophilic phthalic acid esters have been found to impair the human sperm acrosomal reaction likely through the inhibition of the phospholipase A 2 -signaling pathway ( 292 ).…”

Section: Introductionmentioning

confidence: 99%

The adverse role of endocrine disrupting chemicals in the reproductive system

Pan,

Liu,

et al. 2024

Front. Endocrinol.

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Reproductive system diseases pose prominent threats to human physical and mental well-being. Besides being influenced by genetic material regulation and changes in lifestyle, the occurrence of these diseases is closely connected to exposure to harmful substances in the environment. Endocrine disrupting chemicals (EDCs), characterized by hormone-like effects, have a wide range of influences on the reproductive system. EDCs are ubiquitous in the natural environment and are present in a wide range of industrial and everyday products. Currently, thousands of chemicals have been reported to exhibit endocrine effects, and this number is likely to increase as the testing for potential EDCs has not been consistently required, and obtaining data has been limited, partly due to the long latency of many diseases. The ability to avoid exposure to EDCs, especially those of artificially synthesized origin, is increasingly challenging. While EDCs can be divided into persistent and non-persistent depending on their degree of degradation, due to the recent uptick in research studies in this area, we have chosen to focus on the research pertaining to the detrimental effects on reproductive health of exposure to several EDCs that are widely encountered in daily life over the past six years, specifically bisphenol A (BPA), phthalates (PAEs), polychlorinated biphenyls (PCBs), parabens, pesticides, heavy metals, and so on. By focusing on the impact of EDCs on the hypothalamic-pituitary-gonadal (HPG) axis, which leads to the occurrence and development of reproductive system diseases, this review aims to provide new insights into the molecular mechanisms of EDCs’ damage to human health and to encourage further in-depth research to clarify the potentially harmful effects of EDC exposure through various other mechanisms. Ultimately, it offers a scientific basis to enhance EDCs risk management, an endeavor of significant scientific and societal importance for safeguarding reproductive health.

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“…It has been reported that advancing age increases sperm chromatin damage and decreases fertility in peroxiredoxin 6 knockout mice [ 12 ]. Various cell death processes are also involved in spermatogenesis, such as apoptosis and autophagy, and recently, a new form of regulated cell death, ferroptosis, has been reported to be involved in spermatogenesis [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Gss deficiency causes age-related fertility impairment via ROS-triggered ferroptosis in the testes of mice

Zhu,

Cheng,

Wang

et al. 2023

Cell Death Dis

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Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on reducing male fertility is age-dependent and caused by ferroptosis in the testis. The 2-month-old S8/Gss−/− male mice exhibited normal fertility, due to a compensatory increase in GPX4, which prevented the accumulation of ROS. With aging, there was a decline in GPX4 and an increase in ALOX15 levels observed in 8-month-old S8/Gss−/− mice, resulting in the accumulation of ROS, lipid peroxidation, and ultimately testicular ferroptosis. We found that testicular ferroptosis did not affect spermatogonia, but caused meiosis disruption and acrosome heterotopia. Then the resulting aberrant sperm showed lower concentration and abnormal morphology, leading to reduced fertility. Furthermore, these injuries could be functionally rescued by inhibiting ferroptosis through intraperitoneal injection of GSH or Fer-1. In summary, Gss in germ cells play a crucial role in the resistance to oxidative stress injury in aged mice. Our findings deepen the understanding of ferroptosis during spermatogenesis and suggest that inhibiting ferroptosis may be a potential strategy for the treatment of male infertility.

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The Association of Certain Seminal Phthalate Metabolites on Spermatozoa Apoptosis: An Exploratory Mediation Analysis via Sperm Protamine

Cited by 7 publications

References 74 publications

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality

The adverse role of endocrine disrupting chemicals in the reproductive system

Gss deficiency causes age-related fertility impairment via ROS-triggered ferroptosis in the testes of mice

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