Changes in Expression of Connexin Isoforms in the Caudal Epididymis of Adult Sprague-Dawley Rats exposed to Estradiol Benzoate or Flutamide at the Neonatal Age

Abstract

Direct communication between neighboring cells via gap junction in tissue is important for maintenance and regulation of its physiological functions. Each epididymal region has different composition of cell types. It is well recognized that the epididymis is a steroid hormone-responsive tissue. The present study was designed to determine the effect of estradiol benzoate (EB) or flutamide exposured at the early postnatal age on the expression of connexin (Cx) isoforms in the caudal epididymis. The EB or flutamide was subcutaneously administrated to male Spragure Dawley rat at 7 days of age, and expressional changes of Cx isoforms in the adult corpus epididymis were determined by quantitative real-time PCR. The treatment of low-dose EB resulted in decreases of Cx30.3, Cx31.1, Cx37, and Cx45 expression but caused an increase of Cx32 expression. Exposure to high-dose EB led into expressional increases of Cx31, Cx31.1, Cx32, Cx40, and Cx43, even though a decrease of Cx37 expression was found with a high-dose EB treatment. A low-dose flutamide induced increases of Cx31, Cx31.1, Cx32, and Cx43 expression but a decrease of Cx37 expression. Expression of most Cx genes were significantly increased by a high-dose flutamide, while no expressional change of Cx26 and Cx40 was detected by a high-dose flutamide. These results indicate that expression of Cx isoforms in the caudal epididymis is altered by exposure to steroidal compounds at the prepubertal age. It is suggested that a contact with environmental exogenous materials during the early postnatal period would lead to alteration of epididymal functions at the adult.

Effects of Exposure to Estradiol Benzoate or Flutamide at the Weaning Age on Expression of Connexins in the Caudal Epididymis of Adult Rat

“…These observations slightly differ with those from the treatment of Flu at 7 days of age (Lee, 2016). The expressional level of androgen receptor (AR) in the epididymis is gradually increased with postnatal ages, especially during the early postpartum period (You & Sar, 1998).…”

“…It is acceptable to consider that the findings from the current research should be compared with the outcomes conducted with same epididymal segment, rather than with those obtained from the different epididymal segment with same treatment. Thus, the significant findings driven from the present research have been evaluated with those from the treatment of EB or Flu at 7 days of postnatal age, previously reported (Lee, 2016). …”

“…The treatment of a low-dose EB at 7 days of age results in a significant increase of Cx 32 transcript level and causes meaningful decreases of Cx 30.3, Cx 31.1, Cx 37, and Cx 45 transcript levels in the adult caudal epididymis (Lee, 2016). However, as observed in the present research, the same treatment at 21 days of age causes major increases of transcript levels of Cx 26, Cx 31, Cx 37, and Cx 43 but significant reduction of Cx 31.1 and Cx 45 transcript amounts.…”

“…Moreover, expressional patterns of Cx isoforms in a given region of the adult epididymis differ with the time of exposure to EB or Flu during postnatal period (Lee, 2014, 2015a). Most recently, our research has demonstrated expressional changes of Cx isoforms in the adult caudal epididymis administrated with EB or Flu at the early neonatal age (Lee, 2016). From these observations, it has been suggested that the exposure to EB or Flu at the different postnatal age would result in alternation of gene expression of Cx isoforms in the adult caudal epididymis.…”

The effects of flutamide on the neonatal rat hypothalamic–pituitary–adrenal and gonadal axes in response to hypoxia

“…Furthermore, flutamide may act as an agonist in the rat brain and mimic the neuroprotective effects of testosterone (Fanaei, Sadeghipour, Karimian, & Hassanzade, 2013). The agonistic actions of flutamide can occur via mechanisms that depend on the AR in both neuronal and non-neuronal cells (Lee, 2016a(Lee, , 2016bMacLusky et al, 2004;Nguyen et al, 2007) as well as other off-target effects (Foster et al, 2011). Therefore, the suppression of ACTH observed in our study could be the result of AR agonism in the neonatal rat brain.…”