The Impact of Di-2-Ethylhexyl Phthalate on Sperm Fertility

Abstract

A growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2-ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.

Phthalates in albumin from human serum: implications for assisted reproductive technology

“…Fertilizing ability. The fertilizing ability of mouse sperm was impaired or blocked when the sperm were exposed to DEHP (71). After the exposure of sperm to 10 mM of DEHP during IVF, no embryos (0/56) developed into the morula or blastocyst stages compared with vehicle controls (44/48).…”

“…After the exposure of sperm to 10 mM of DEHP during IVF, no embryos (0/56) developed into the morula or blastocyst stages compared with vehicle controls (44/48). This concentration of DEHP completely blocked development to morula and blastocysts by preventing sperm penetration of oocytes, as assessed by the formation of pronuclei after IVF (71). When the sperm were incubated with 2 mM of DEHP and then used for IVF with uncontaminated oocytes, approximately 50% of the fertilized eggs progressed to the blastocyst stage, demonstrating a dose-dependent effect of DEHP on sperm (71).…”

“…In contrast, human CatSper is not activated by 0.1-, 1-, or 10-mM DEHP or MEHP (73). There was no effect of 2and 10-mM DEHP on CatSper in mouse sperm (71). However, MEHP, but not DEHP, increased Ca 2þ influx in human sperm using a fluorescent Ca 2þ indicator, Fluo-4 AM (74).…”

“…Tyrosine phosphorylation and acrosome reaction. In the mouse, 10-mM DEHP altered the timing of protein tyrosine phosphorylation and lowered the number of sperm that underwent a spontaneous acrosome reaction (71). The amount of tyrosine phosphorylated proteins increased after DEHP exposure, peaked at 1 hour, and declined by 2 hours (71).…”

Taurine ameliorates cytotoxic effects of Di(2‐ethylhexyl) phthalate on Leydig cells

“…Di(2‐ethylhexyl) phthalate (DEHP) has the greatest application among phthalates (Jurewicz et al., 2013; Latini et al., 2010). DEHP causes a decline in the testis weight, inducing testicular damages, worsening the quality of semen and reducing the fertility index (Khasin et al., 2020; Qin et al., 2018; Sumner et al., 2019). Leydig cells have also targeted by the DEHP (Rowdhwal & Chen, 2018).…”