Effects of Maternal Exposure to 3,3′,4,4′,5‐Pentachlorobiphenyl (PCB126) or 3,3′,4,4′,5,5′‐Hexachlorobiphenyl (PCB169) on Testicular Steroidogenesis and Spermatogenesis in Male Offspring Rats

Abstract

On days 7-21 of gestation, Sprague-Dawley rats were orally administered 3 or 30 mug/kg/d of 3,3',4,4',5-pentachlorobiphenyl (PCB126) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB169) daily. Their male offspring were autopsied at 3, 6, and 15 weeks after birth to investigate the effects of the 2 polychlorinated biphenyls (PCBs) on spermatogenesis and steroidogenesis in their testes. PCB treatment caused a decrease in the area ratio of 3beta-hydroxysteroid dehydrogenase (HSD)-expressing cells (Leydig cells)/testis at 3 weeks after birth. When PCB126 was administered to pregnant rats, the plasma testosterone levels in their offspring were decreased at 3 weeks. The expression levels of P450scc, 3beta-HSD, and P450(17alpha) mitochondrial RNAs (mRNAs) were unchanged, although the StAR (steroidogenic acute regulatory protein) mRNA expression level was increased at 6 weeks. On the other hand, when PCB169 was administered, plasma testosterone levels were decreased at 3 and 6 weeks and were increased at 15 weeks. Plasma luteinizing hormone (LH) levels were decreased at 6 weeks, and plasma follicle-stimulating hormone (FSH) levels were increased at 15 weeks. The expression levels of 3beta-HSD and P450(17alpha) were increased, and the mRNA level of 5alpha-reductase 1 was decreased at 15 weeks. PCB169 treatment suppressed the conversion of round spermatids between stages VII and VIII. These results indicate that in utero and lactational exposure to PCB126 or PCB169 decreases plasma testosterone levels in 3-week-old rats, with no change in the expression levels of the mRNAs of enzymes, and that PCB169 inhibits testicular steroid synthesis more strongly than PCB126. PCB169 greatly altered the concentration of testosterone, indicating a stronger inhibitory effect on spermatogenesis. Low testosterone and LH levels in prenatally PCB169-exposed rats until 6 weeks after birth presumably retard the functional differentiation of testicular Leydig cells; however, the increased testosterone levels at 15 weeks suggest that Leydig cells in PCB-exposed rats are virtually mature by the 15th week.

Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle

“…A similar reduction in testosterone was also observed in male monkeys exposed to A1242 during adulthood [81], and male rats gestationally exposed to PCB126 [44]. Conversely, embryonic treatment with PCB169 causes an increase in adult male testosterone levels in rats [28], suggesting that PCB effects on steroid hormone levels may be congener specific.…”

“…For instance, Kaya et al [27] observed decreased levels of estradiol and testosterone in female rats exposed to a reconstituted mixture of PCBs throughout the period of gestation and lactation, while only serum testosterone was reduced in exposed males. Similarly, gestational exposure to the individual PCB congeners PCB126 or PCB169 resulted in reduced levels of serum testosterone in weanling males [28]. Gestational exposure to A1254 caused reductions in serum estradiol in weanling male rats, while female estradiol levels were not affected [29].…”

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

“…Our laboratory has previously demonstrated that administration of two polychlorobiphenyls (PCB126 and PCB169) with different structures to pregnant rats during the same period of pregnancy as in the present study causes postnatal decreases in the level of testosterone and percentage of testicular Leydig cells in pups [36]. However, in the present study, DES administration did not influence the total volume of Leydig cells, suggesting that it has no inhibitory effect on their development.…”

Two-hit exposure to polychlorinated biphenyls at gestational and juvenile life stages: 2. Sex-specific neuromolecular effects in the brain

“…The lack of change in serum concentrations of E 2 or T is in agreement with some studies (Dickerson et al, 2011b; Steinberg et al, 2008; Walker et al, 2014). Other studies have shown that more highly chlorinated PCB congeners tended to reduce E 2 and T concentrations (Hany et al, 1999; Kaya et al, 2002; Muto et al, 2003; Yamamoto et al, 2005). Similarly, A1221 had no effect on T3 or T4 in the current study, but more highly chlorinated congeners are well known to decrease T3 and T4 (Giera et al, 2011; Khan et al, 2002; Sauer et al, 1994; Ulbrich and Stahlmann, 2004).…”