Modification of Gene Expression of Connexins in the Rat Corpus Epididymis by Estradiol Benzoate or Flutamide Exposure at the Early Neonatal Age

Abstract

Cell-cell direct communication through channel-forming molecules, connexin (Cx), is essential for a tissue to exchange signaling molecules between neighboring cells and establish unique functional characteristics during postnatal development. The corpus epididymis is a well-known androgen-responsive tissue and involves in proper sperm maturation. In the present research, it was attempted to determine if expression of Cx isoforms in the corpus epididymis in the adult is modulated by exposure to estrogenic or anti-androgenic compound during the early postnatal period. The neonatal male rats at 7 days of age were subcutaneously injected by estradiol benzoate (EB) at low-dose (0.015 mg/kg body weight) or high-dose (1.5 mg/kg body weight) or flutamide (Flu) at low-dose (500 mg/kg body weight) or high-dose (50 mg/kg body weight). The corpus epididymis collected at 4 months of age was subjected to evaluate expressional changes of Cx isoforms by quantitative real-time PCR. Treatment of low-dose EB resulted in increases of Cx32, Cx37, and Cx45 transcript levels, while exposure to high-dose EB decreased expression of Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45. Treatments of Flu caused significant decreases of expression of all examined Cx isoforms, except Cx37 and Cx43 shown no expressional change with high-dose Flu treatment. These findings imply that expression of most Cx isoforms present in the corpus epididymis would be transcriptionally regulated by actions of androgen and/or estrogen during postnatal period.

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

“…Especially, this research shows expressional change of Cx 43 in the caudal epididymis, but not in the corpus epididymis (Lydka et al, 2011). As seen in our previous (Lee, 2013 & 2015) and present researches, Cx 43 is the most predominant form of Cx isoforms in the epididymis. Thus, it is important to notice the opposite effects of high-dose EB and low-dose flutamide treatments on expression of Cx 43 in the corpus and caudal epididymis.…”

“…For example, in the corpus epididymis, gene expression of Cx 26 was significantly decreased by a highdose (1.5 mg/kg BW) EB and a low-dose (500 mg/kg BW) and a high-dose (50 mg/kg BW) flutamide treatment (Lee, 2015), while there was no significant change on Cx 26 in the caudal epididymis. These findings suggest that expression of Cx 26 gene could be regulated by estrogenic and/or androgenic materials in segment-specific manner within the epididymis.…”

“…It is noteworthy that expression of Cx 30.3, Cx 31.1, Cx 37, and Cx 45 genes by the treatment of a low-dose (0.015 mg/kg BW) EB at 7 days of postnatal age is significantly decreased in the caudal epididymis, but either no change or significantly increased in the corpus epididymis of adult rat (Lee, 2015). In addition, expression of Cx 32 gene is induced by the same treatment in both caudal and corpus epididymis (Lee, 2015).…”

“…In addition, expression of Cx 32 gene is induced by the same treatment in both caudal and corpus epididymis (Lee, 2015). Moreover, the treatment of a low-dose EB at 7 days of postnatal age doesn’t influence on expression of Cx 26, Cx 31, Cx 40, and Cx 43 gene in bother caudal and corpus epididymis (Lee, 2015). Such ununiformed outcomes on expressional patterns of Cx isoforms obtained from the corpus and caudal epididymis by the treatment of a low-dose EB could not be simply explainable at this point.…”

“…In the most of cases, these treatments at 7 days of postnatal age result in significant decreases of gene expression of Cx isoforms in the adult corpus epididymis (Lee, 2015), but the opposite results are acquired with the adult caudal epididymis treated with same materials. The exceptions are Cx 26, Cx 30.3, and Cx 45 in a high-dose EB treatment, Cx 26, Cx 30.3, Cx 40, and Cx 45 in a low-dose flutamide treatment, and Cx 26, Cx 37, Cx 40, and Cx 43 (Lee, 2015). Lydka et al (2011) have demonstrated that the administration of flutamide in prenatal boar results in morphological and functional abnormalities in the epididymis of adult boar.…”