Di-(2-ethylhexyl) Phthalate (DEHP) and Uterine Histological Characteristics

Abstract

Phthalates have a long industrial history. It is suspected that phthalates and their metabolites have detrimental effects on reproduction and development. They are well-known for their anti-androgenic effects. Several studies have indicated that phthalates and their metabolites are reprotoxic in males and endocrine disruptors. Reproduction and embryogenesis occur in the uterus of female eutherian mammals. A horizontal analytical method is preferred to elucidate the toxic effects of phthalates on human reproduction. Nevertheless, there are vast numbers of known phthalates and not all of their modes of action have been clarified. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer and has been the subject of numerous toxicological studies. However, few of these have reported on the toxic effects of DEHP, its metabolites, other phthalates, or mixtures on female reproduction. Acute and high doses of DEHP adversely affect uterine histology. Recently, it was disclosed that chronic exposures to low doses of DEHP have endocrine disruption efficacy. DEHP induces various cellular responses including modulation of the expression and regulation of steroid hormone receptors and transcription and paracrine factors. Uteri do not respond uniformly to DEHP exposure. The phenotypic manifestations and effects on fertility in response to DEHP and its metabolites may vary with species, developmental stage, and generation. Hence, DEHP exposure may histological alter the uterus and induce endometriosis, endometriosis, hyperplasia, myoma, and developmental and reproductive toxicity.

A Chronic-Low-Dose Exposing of DEHP with OECD TG 443 Altered the Histological Characteristics and Steroidogeic Gene Expression of Adrenal Gland in Female Mice

“…As the previous results, the possibility of chronic exposures to low-dose DEHP is an effect as EDC in the uterus without effect on F1 fertility (Cha et al, 2017;Cheon, 2020). Chronic low dose exposure of DEHP caused increase the uterine wet weight, endometrial thickness, and the number of glands (Cheon, 2020). Besides, it caused decreased expression of estrogen receptors in uterus.…”

“…Recently, there are many scientists suggest that low dose phthalate impacts on health of animals such as fertility and steroidogenesis (Bloom et al, 2015) and become a big issue in this field (Vandenberg et al, 2019). As the previous results, the possibility of chronic exposures to low-dose DEHP is an effect as EDC in the uterus without effect on F1 fertility (Cha et al, 2017;Cheon, 2020). Chronic low dose exposure of DEHP caused increase the uterine wet weight, endometrial thickness, and the number of glands (Cheon, 2020).…”

“…In the histological characters in chronic low-dose DEHP groups with H-E and trichrome staining, showed normal cell shapes and arrangement in the zonas with thickened ZFs, but not change in ECM localizing patterns. DEHP has a function as a modulator of cell proliferation and differentiation in various cells such as T-47D cell, endometrial stromal cell, thyroid cells, etc (Richardson et al, 2018;Crobeddu et al, 2019;Cheon, 2020). It is may cause of the increase of wet weight of adrenal gland.…”

“…Initial reproductive and developmental toxicity studies on phthalates did in pregnant female rodent and fetus. It showed various toxicity in implantation, reabsorptions, decreased body weight, and increased malformations in dose and developmental stage dependent manners (Tyl et al, 1988;Cheon, 2020). The well examined target organs of DEHP include ovary (Komar et al, 2001), testis (Li et al, 2014), endometrium, placenta, liver (Lovekamp-Swan & Davis, 2003, placenta (Martínez-Razo et al, 2021), renal, lung, immune system, brain development, and heart tissue (Martínez-Razo et al, 2021).…”

The impact of phthalate on reproductive function in women with endometriosis

“…Several evidences suggested that environmental pollutants might be involved in the pathogenesis of endometriosis 7‐11 . These endocrine‐disrupting chemicals interrupt hormonal homeostasis and result in estrogen signaling changes 11‐23 …”