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

Michala R. Birch, Mathias Johansen, Niels E. Skakkebæk, Anna-Maria Andersson, Anders Rehfeld*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

12 Citations (Scopus)
15 Downloads (Pure)

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.

Original languageEnglish
Article number107399
JournalEnvironment International
Volume167
Number of pages15
ISSN0160-4120
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022

Keywords

  • CatSper
  • Endocrine disruption
  • Fertility
  • Male reproduction
  • Pesticides

Cite this