[Study of Pregnancy Exposure to PFOS on Reproductive Toxicities and Mechanism in Male Offspring Rats].

OBJECTIVE: To explore the effects of testosterone synthesis in adult leydig cell (ALC) of male rats exposed by perfluorooctane sulfonate (PFOS) during pregnancy. METHODS: At gestations 12 day, the pregnant rats were exposed to PFOS (5 mg/kg, PFOS group) or 0.5% Tween (control group) by gavage, once a day for 8 consecutive days. On postnatal day (PND) 70, several indexes of male offspring rats were measured including body mass, testicular coefficient, sperm count, serum testosterone concentration. The mRNA levels of ALC associated with testosterone synthesis were detected by real-time quantitative RT-PCR. RESULTS: The result showed that sperm count and serum testosterone concentration decreased in male offspring rats of PFOS group (P < 0.05), and body mass was significantly lower (P < 0.001). The expression of steroidogenic acute regulatory factor (Star), scavenger receptor class B type 1 (Scarb1), Cyp11a1 (coding gene of cytochrome P450 side chain cleavage) and Hsd17b3 (coding gene of 17ß-hydroxysteroid dehydrogenase) were down regulated (P < 0.05), no significant statistical difference was observed on the mRNA level of insulin-like growth factor-1 (Igf1) and insulin-like factor 3 (Insl3). CONCLUSION: Gestational exposure to PFOS can inhibit the mRNA levels associated with testosterone synthesis, and decrease the ability of testosterone synthesis in ALC of male offspring rats.

Alterations in gene expression and steroidogenesis in the testes of transient cerebral ischemia in male rats.

BACKGROUND: Serum testosterone levels have been found lower in acute ischemic stroke male patients. However, the exact mechanism remains unclear. In the present study, we measured serum testosterone levels, steroidogenesis- related genes and Leydig cells number in experimental transient cerebral ischemia male rats to elucidate the mechanism. METHODS: The middle cerebral arteries of adult male Sprague-Dawley rats were sutured for 120 minutes and then sacrificed after 24 hours. Blood was collected for measurement of serum testosterone, follicular stimulating hormone and estradiol levels, and testes were collected for measurement of steroidogenesis-related gene mRNA levels and number of Leydig cells. RESULTS: Serum testosterone levels in rats after cerebral ischemia were significantly lower (0.53 ± 0.16) ng/ml, n = 7, mean ± SE) compared with control ((2.33 ± 0.60) ng/ml, n = 7), while serum estradiol and follicular stimulating hormone levels did not change. The mRNA levels for luteinizing hormone receptor (Lhcgr), scavenger receptor class B member 1 (Scarb1), steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (Cyp11a1), 3ß-hydroxysteroid dehydrogenase 1 (HSD3ß1), 17α-hydroxylase/20-lyase (Cyp17a1) and membrane receptor c-kit (kit) were significantly downregulated by cerebral ischemia, while luteinizing hormone, Kit ligand (KitL), 17ß-hydrosteroid dehydrogenase 3 (HSD17ß3) and 5α-reductase (Srd5a1) were not affected. We also observed that, relative to control, the Leydig cell number did not change. CONCLUSIONS: These results indicate that transient cerebral ischemia in the brain results in lower expression levels of steroidogenesis-related genes and thus lower serum testosterone level. Transient cerebral ischemia did not lower the number of Leydig cells.

Effects of genistein and equol on human and rat testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 activities.

The objective of the present study was to investigate the effects of genistein and equol on 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) in human and rat testis microsomes. These enzymes (3beta-HSD and 17beta-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17alpha-hydroxylase/17-20 lyase), catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3beta-HSD activity (0.2 micromol L(-1) pregnenolone) with half-maximal inhibition or a half-maximal inhibitory concentration (IC(50)) of 87 +/- 15 (human) and 636 +/- 155 nmol L(-1) (rat). Genistein's mode of action on 3beta-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD(+). There was no difference in genistein's potency of 3beta-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3beta-HSD, genistein had lesser effects on human and rat 17beta-HSD3 (0.1 micromol L(-1) androstenedione), with an IC(50) >or= 100 micromol L(-1). On the other hand, equol only inhibited human 3beta-HSD by 42%, and had no effect on 3beta-HSD and 17beta-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3beta-HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.