Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

Abstract

Humans can be exposed to endocrine disruptors (EDs) in numerous ways. EDs can interfere with endogenous hormones at different levels, resulting in numerous adverse human health outcomes, including immunotoxicity. In this regard, this study aimed to investigate in vitro the possible effects of EDs on immune cells and possible gender differences. Peripheral blood mononuclear cells from healthy humans, both males and females, were exposed to 6 different EDs, namely atrazine (herbicide), cypermethrin (insecticide), diethyl phthalate (plasticizer), 17α-ethynylestradiol (contraceptive drug), perfluorooctanesulfonic acid (persistent organic pollutant), and vinclozolin (fungicide). We evaluated the effect of EDs on RACK1 (receptor for activated C kinase 1) expression, considering it as a bridge between the endocrine and the immune system, and putatively used as screening tool of immunotoxic effects of EDs. The exposure to EDs resulted at different extent in alteration in RACK1 expression, pro-inflammatory activity, natural killer lytic ability, and lymphocyte differentiation, with sex-related differences. In particular, diethyl phthalate and perfluorooctanesulfonic acid resulted the most active EDs tested, with gender differences in terms of effects and magnitude. The results from our study evidenced the ability of EDs to directly affect immune cells.

A comprehensive battery of flow cytometric immunoassays for the in vitro testing of chemical effects in human blood cells

“…The fact that we did not take the sex of the donors into account is a limitation of the present study. However, others have suggested using male donors for the initial testing and then confirming the effects in women at a similar stage of the menstrual cycle ( 57 , 58 ). It is also possible that in vitro testing of chemicals may not reflect the real situation in vivo , where the chemicals are subject to metabolism that may either activate or inactivate them, depending on the mode of action ( 59 ).…”

GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments

“…A remarkable point is that GPER promotes monocyte activation and LPS-induced pro-inflammatory cytokines [56], providing a potential strategy to enhance the immune response. Additionally, GPER has multiple ligands, including some of the drugs used for cancer treatment and xenobiotics; thus, representing an advantage for cancer development and a challenge for medical procedures [20,21,[92][93][94][95][96][97].…”

“…However, VIN, atrazine (ATZ), and cypermethrin (CYP) decrease these proteins [96]. On the other hand, the EE and VIN inhibit RACK1 in a primary culture of female donors [97], highlighting the role of GPER in innate immune response regulation.…”

Unveiling the Immune Microenvironment’s Role in Breast Cancer: A Glimpse into Promising Frontiers

“…The therapeutic resistance to radiation, chemotherapy, and immunotherapy is largely attributed to IL-10 generated by TAMs and activation of the IL-10/STAT3/BCL-2 signaling pathway [120,150]. These network relationships are not only dictated by treatment but also by environmental factors, such as endocrine-active substances (EASs) and endocrine-disrupting chemicals (EDCs) that, by altering the activity of the immune system, can contribute to setting an unhealthy pro-tumor inflammation (PTI) (directly correlated to TNF-α and monocytes/macrophages action) [38,[152][153][154], thus facilitating the oncogenic process via the promotion of tumor growth, survival, and metastasis and suppressing the anti-tumoral immune response, shaping pivotal TME characteristics [39].…”