Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies

Abstract

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

“…These EDCs were selected due to their presence and/or persistence in the environment, ubiquitous human exposure, and links to reproductive dysfunction. The effects of EDCs on other aspects of fertility, such as gametogenesis, uterine function, placentation, fetal development, and so forth, are outside of the scope of this review but are reviewed elsewhere (Basak et al, 2020 ; Caserta et al, 2021 ; Ge et al, 2019 ; Gingrich et al, 2020 ; Gore et al, 2015 ; Spencer et al, 2012 ; Warner et al, 2021 ).…”

Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review

“…In many cases, contact with EDCs does not have immediate effects. Exposure before puberty or during intrauterine life can, for example, lead to significant effects on fertility after many years [ 66 ]. The foundations of many adult pathologies could be traced back to exposure to EDCs during life in utero.…”

Impact of Triclosan on Female and Male Reproductive System and Its Consequences on Fertility; A Literature Review

“…In the study on inseminated mice, exposure to high doses of TCS decreased the number of implantation sites. Moreover, administration of this chemical combined with bisphenol A accelerated this decreasing effect ( 23 ). TCS has potential to decrease estrogen sulfotransferase (EST) activity, leading to placental thrombosis and increasing the risk of miscarriage in humans and mice ( 24 ).…”