In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel

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Standard

In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel. / Birch, Michala R.; Johansen, Mathias; Skakkebæk, Niels E.; Andersson, Anna-Maria; Rehfeld, Anders.

In: Environment International, Vol. 167, 107399, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Birch, MR, Johansen, M, Skakkebæk, NE, Andersson, A-M & Rehfeld, A 2022, 'In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel', Environment International, vol. 167, 107399. https://doi.org/10.1016/j.envint.2022.107399

APA

Birch, M. R., Johansen, M., Skakkebæk, N. E., Andersson, A-M., & Rehfeld, A. (2022). In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel. Environment International, 167, [107399]. https://doi.org/10.1016/j.envint.2022.107399

Vancouver

Birch MR, Johansen M, Skakkebæk NE, Andersson A-M, Rehfeld A. In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel. Environment International. 2022;167. 107399. https://doi.org/10.1016/j.envint.2022.107399

Author

Birch, Michala R. ; Johansen, Mathias ; Skakkebæk, Niels E. ; Andersson, Anna-Maria ; Rehfeld, Anders. / In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel. In: Environment International. 2022 ; Vol. 167.

Bibtex

@article{44936ffe3ae0461191e231c0e5311cdc,
title = "In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel",
abstract = "Background: Ca2+-signaling controls sperm cell functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to interfere with normal Ca2+-signaling in human sperm cells through an activation of the sperm-specific CatSper Ca2+-channel, which is vital for normal male fertility. Objectives: We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca2+-signaling and function in human sperm cells. Methods: Effects of the pesticides on Ca2+-signaling in human sperm cells were evaluated using a Ca2+-fluorometric assay. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function and viability were assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm–mucus penetration assay. Results: 28 of 53 pesticides were found to induce Ca2+-signals in human sperm cells at 10 µM. The majority of these 28 active pesticides induced Ca2+-signals through CatSper and interfered with subsequent Ca2+-signals induced by the two endogenous CatSper ligands progesterone and prostaglandin E1. Multiple active pesticides were found to affect Ca2+-mediated sperm functions and viability at 10 µM. Low nM dose mixtures of the active pesticides alone or in combination with other environmental chemicals were found to significantly induce Ca2+-signals and inhibit Ca2+-signals induced subsequently by progesterone and prostaglandin E1. Conclusions: Our results show that pesticides, both alone and in low nM dose mixtures, interfere with normal Ca2+-signaling in human sperm cells in vitro in low nM concentrations. Biomonitoring of the active pesticides in relevant matrices such as blood and reproductive fluids is very limited and the effects of real time human pesticide exposure on human sperm cells and fertility thus remains largely unknown. To which extent human pesticide exposure affects the chances of a successful fertilization in humans in vivo needs further research.",
keywords = "CatSper, Endocrine disruption, Fertility, Male reproduction, Pesticides",
author = "Birch, {Michala R.} and Mathias Johansen and Skakkeb{\ae}k, {Niels E.} and Anna-Maria Andersson and Anders Rehfeld",
note = "Publisher Copyright: {\textcopyright} 2022",
year = "2022",
doi = "10.1016/j.envint.2022.107399",
language = "English",
volume = "167",
journal = "Environment international",
issn = "0160-4120",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel

AU - Birch, Michala R.

AU - Johansen, Mathias

AU - Skakkebæk, Niels E.

AU - Andersson, Anna-Maria

AU - Rehfeld, Anders

N1 - Publisher Copyright: © 2022

PY - 2022

Y1 - 2022

N2 - Background: Ca2+-signaling controls sperm cell functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to interfere with normal Ca2+-signaling in human sperm cells through an activation of the sperm-specific CatSper Ca2+-channel, which is vital for normal male fertility. Objectives: We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca2+-signaling and function in human sperm cells. Methods: Effects of the pesticides on Ca2+-signaling in human sperm cells were evaluated using a Ca2+-fluorometric assay. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function and viability were assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm–mucus penetration assay. Results: 28 of 53 pesticides were found to induce Ca2+-signals in human sperm cells at 10 µM. The majority of these 28 active pesticides induced Ca2+-signals through CatSper and interfered with subsequent Ca2+-signals induced by the two endogenous CatSper ligands progesterone and prostaglandin E1. Multiple active pesticides were found to affect Ca2+-mediated sperm functions and viability at 10 µM. Low nM dose mixtures of the active pesticides alone or in combination with other environmental chemicals were found to significantly induce Ca2+-signals and inhibit Ca2+-signals induced subsequently by progesterone and prostaglandin E1. Conclusions: Our results show that pesticides, both alone and in low nM dose mixtures, interfere with normal Ca2+-signaling in human sperm cells in vitro in low nM concentrations. Biomonitoring of the active pesticides in relevant matrices such as blood and reproductive fluids is very limited and the effects of real time human pesticide exposure on human sperm cells and fertility thus remains largely unknown. To which extent human pesticide exposure affects the chances of a successful fertilization in humans in vivo needs further research.

AB - Background: Ca2+-signaling controls sperm cell functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to interfere with normal Ca2+-signaling in human sperm cells through an activation of the sperm-specific CatSper Ca2+-channel, which is vital for normal male fertility. Objectives: We investigated 53 pesticides for their ability to interfere with CatSper mediated Ca2+-signaling and function in human sperm cells. Methods: Effects of the pesticides on Ca2+-signaling in human sperm cells were evaluated using a Ca2+-fluorometric assay. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function and viability were assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm–mucus penetration assay. Results: 28 of 53 pesticides were found to induce Ca2+-signals in human sperm cells at 10 µM. The majority of these 28 active pesticides induced Ca2+-signals through CatSper and interfered with subsequent Ca2+-signals induced by the two endogenous CatSper ligands progesterone and prostaglandin E1. Multiple active pesticides were found to affect Ca2+-mediated sperm functions and viability at 10 µM. Low nM dose mixtures of the active pesticides alone or in combination with other environmental chemicals were found to significantly induce Ca2+-signals and inhibit Ca2+-signals induced subsequently by progesterone and prostaglandin E1. Conclusions: Our results show that pesticides, both alone and in low nM dose mixtures, interfere with normal Ca2+-signaling in human sperm cells in vitro in low nM concentrations. Biomonitoring of the active pesticides in relevant matrices such as blood and reproductive fluids is very limited and the effects of real time human pesticide exposure on human sperm cells and fertility thus remains largely unknown. To which extent human pesticide exposure affects the chances of a successful fertilization in humans in vivo needs further research.

KW - CatSper

KW - Endocrine disruption

KW - Fertility

KW - Male reproduction

KW - Pesticides

U2 - 10.1016/j.envint.2022.107399

DO - 10.1016/j.envint.2022.107399

M3 - Journal article

C2 - 35853389

AN - SCOPUS:85134706743

VL - 167

JO - Environment international

JF - Environment international

SN - 0160-4120

M1 - 107399

ER -

ID: 322279789