Lactational exposure of phthalate causes long-term disruption in testicular architecture by altering tight junctional and apoptotic protein expression in Sertoli cells of first filial generation pubertal Wistar rats

Abstract

<jats:p> Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant and a well-known endocrine disruptor (ED) that interferes with the reproductive function in both humans and animals. This study aimed to find out the impact of lactational exposure of DEHP in testes of first filial generation (F<jats:sub>1</jats:sub>) progeny male rat postnatal day (PND)-60. Lactating dams were orally treated with DEHP (0, 1, 10 and 100 mg/kg body weight/day, respectively) from the PND-1 to PND-21. Rats were killed at PND 60. Testes were removed and used for histological analysis and for isolation of Sertoli cells (SCs). The histoarchitecture of DEHP-treated rats showed disturbed testicular structure. DEHP-treated rats also showed increased oxidative stress by decreasing antioxidant levels in the SCs; it disrupted SC tight junctional proteins occludin, claudin, junctional adhesion molecule, zona occludens protein-1 (ZO-1), zona occludens protein-2 (ZO-2), and afadin-6 (AF-6), increased apoptosis by altering the apoptotic genes Bax, cytochrome c, caspase-8, -9, -3 and antiapoptotic gene Bcl-2. It is concluded that early postnatal exposure to DEHP disturbs histoarchitecture of testis and SC function in pubertal Wistar rats. </jats:p>

Effect of mono‐(2‐ethylhexyl) phthalate (MEHP) on proliferation of and steroid hormone synthesis in rat ovarian granulosa cells in vitro

“…DEHP exposure has also been shown to produce reproductive toxicity in animal models. Sekaran et al () showed that early postnatal exposure to DEHP disturbed the histoarchitecture of the testis and Sertoli cells function in pubertal Wistar rats. Hirosawa, Yano, and Suzuki () found that DEHP administered orally for 26 weeks caused a continuous diestrus phase in female rats.…”

Lactational exposure of polychlorinated biphenyls downregulates critical genes in Leydig cells of F1 male progeny (PND21)

“…The testes and accessory sex organ weight decreased data are in agreement with studies, indicating that adult male rat treated with Aroclor 1254 (Senthil kumar et al., ). In addition, one of other endocrine disrupter di(2‐ethylhexyl) phthalate (DEHP) too evidenced in F1 offspring drops in bodyweight and accessory organ weight (Sekaran et al., ). Our previous studies showed that PCB induces oxidative stress and decreased activities of antioxidant enzymes and disrupts the junctional parameters in testicular Leydig and Sertoli cells of adult animals (Krishnamoorthy et al., ; Murugesan et al., ).…”

“…Predominant testicular gap junctional protein connexin 43 is located between neighbouring Sertoli cells and between Sertoli cells and germ cells. Exposure of DEHP affects Leydig cellular steroidogenesis on F1 male pups (Sekaran et al., ).…”

In Utero Exposure to Phthalate Downregulates Critical Genes in Leydig Cells of F1 Male Progeny

“…Our previous studies have demonstrated effects of DEHP in modulating the expression of Sertoli cell tight junctional and apoptotic protein through elevated free radical generation and oxidative stress [Sekaran et al, ]. The studies suggested that DEHP exposure can interfere with intercellular communication and possibly disrupt the process of spermatogenesis.…”