To assess the effects of a single supraphysiological postnatal administration of a progestogen on uterine glands in dogs, 10 females were randomly assigned to a medroxyprogesterone acetate 35 mg (MPA; n = 6) or placebo (n = 4) group within the first 24 h of birth. The safety of the treatment was also evaluated. A transient mild clitoris enlargement appeared in MPA-treated females. Microscopic postpubertal uterine assessment revealed the presence of uterine glands in all cases without significant differences in the area occupied by the glands per µm2 of endometrium nor in the height of the uterine epithelium.
Animals ; Animals, Newborn ; Clitoris/drug effects ; Dogs ; Epithelium/*drug effects ; Female ; Medroxyprogesterone Acetate/*pharmacology ; Organ Size/drug effects ; Random Allocation ; Sexual Maturation/drug effects ; Uterus/*drug effects

AIMTo evaluate the effect of acute lead chloride exposure on testis and sperm parameters in mice.

METHODSPbCl2, 74 mg/kg, was daily administered to sexually mature male mice for 3 days and the effects on the testicular histology and ultrastructure as well as the motility and density of spermatozoa in cauda epididymis were observed. An additional group of mice were treated for 1-3 days and were allowed to recover for 32 days to determine the reversibility of lead-induced changes.

RESULTSThe testicular weight, seminiferous tubular diameter and sperm counts were significantly decreased following 3 days of PbCl2 treatment, but were unaffected by shorter-term exposures. The changes caused by lead are mostly reversible.

CONCLUSIONAcute lead chloride exposure injures the fertility parameters of male mice and the effects are partially reversible.

Animals ; Epididymis ; drug effects ; physiology ; Lead ; pharmacology ; Male ; Mice ; Microscopy, Electron ; Sexual Maturation ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; physiology ; Spermatozoa ; cytology ; drug effects ; ultrastructure

OBJECTIVETo establish the rat model of estradiol valerate medication in early pregnancy, and to investigate the effects of estradiol valerate on the development of the reproductive system of the first filial generation (F1) male rats by evaluating the anogenital distance (AGD) and the development of the testis and epididymis.

METHODSPregnant SD rats were divided at random into a blank control group and a low dose, a medium dose and a high dose medication group to receive intragastric estradiol valerate at 0.2 mg/kg, 0.5 mg/kg and 0.8 mg/kg, respectively. The newborn F1 male rats were normally fed. Their anogenital distances were measured on postnatal day (PND) 3 and 21, the organ coefficients of the testis and epididymis (testicular and epididymal weight g/body weight 100 g) were obtained on PND 60, the morphological changes of spermatogenic cells were observed by testis biopsy, and the diameter of the seminiferous tubule and epithelial height were measured.

RESULTSThere was no significant difference between the control and medicated F1 male rats in AGD on PND 3 and 21 (P > 0.05), nor in the organ coefficients of the testis and epididymis on PND 60 (P > 0.05), nor in the diameter of the seminiferous tubule and epithelial height.

CONCLUSIONMedication of estradiol valerate (0.2 -0.8 mg/kg) to rats in early pregnancy neither significantly affects the reproductive system development, nor induces obvious histological changes of the testis in the sexual maturation period of their F1 males.

Animals ; Estradiol ; analogs & derivatives ; pharmacology ; Female ; Male ; Maternal Exposure ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Sexual Maturation ; drug effects ; Testis ; drug effects ; growth & development

Detrimental effects of tributyltin (TBT) chloride on the reproductive system were investigated in pubertal male rats. Sixty Sprague-Dawley rats aged with 35 days were assigned to six different groups; negative control receiving vehicle, positive control receiving methyltestosterone (10 mg/kg B.W.), TBT chloride (5 mg/kg B.W., 10 mg/kg B.W., and 20 mg/kg B.W.), and a combination of TBT chloride (10 mg/kg B.W.) and flutamide (10 mg/kg B.W). The animals were treated with test compounds by oral gavage daily for 10 days and sacrificed on the next day of the final treatment. The treatment with TBT chloride at the doses of 10 and 20 mg/kg B.W. significantly decreased seminal vesicle weights, compared to the negative control. The combined treatment of TBT chloride and flutamide caused a significant decrease in accessory sex organ weights, compared to the control and TBT chloride treatments. The treatment with TBT chloride or in the combination with flutamide increased detached debris and sloughed cells in the tubules of epididymis and narrowed seminal vesicles. In addition, the combined treatment with TBT chloride and flutamide caused a noticeable increase in serum androgen level, compared to the negative control.These results suggest that TBT chloride exposed during pubertal period cause partial reproductive disorders in male rats.
Animals ; Body Weight ; Epididymis/drug effects ; Flutamide/pharmacology ; Genitalia, Male/*drug effects ; Male ; Methyltestosterone/pharmacology ; Organ Size ; Prostate/drug effects ; Rats ; Rats, Sprague-Dawley ; Seminal Vesicles/drug effects ; *Sexual Maturation/drug effects ; Testis/drug effects ; Trialkyltin Compounds/*pharmacology

The effects of ethylene glycol monoethyl ether (EGEE) on testicular cell populations in pubertal (5 weeks old) and adult (9 weeks old) male rats were investigated by a flow cytometric method. A total of 50 rats (in number, 25 pubertal and 25 adult rats) was divided into 5 experimental groups including 0 (control), 50, 100, 200, and 400 mg EGEE/kg of body weight. The animals were administered by gavage for 4 weeks. In adult rats, the treatment of EGEE at the dose of 400 mg/kg of body weight decreased significantly the populations of haploid, while it increased those of diploid and tetraploid cells. In pubertal rats, the treatment of EGEE at the dose of 400 mg/kg of body weight caused only minimal changes in the relative percent of testicular cell types. These results suggest that the effects of EGEE on testicular function in pubertal rats appear to be less pronounced than in adult rats.
Animals ; Dose-Response Relationship, Drug ; Ethylene Glycols/*toxicity ; Male ; Organ Size/drug effects ; Rats ; Sexual Maturation/*drug effects ; Solvents/*toxicity ; Spermatogenesis/*drug effects ; Testis/drug effects/*pathology ; Time Factors

OBJECTIVETo investigate the effects of prepubertal exposure to diethylstilbestrol (DES) on the testicular development and function of Sprague-Dawley (SD) rats.

METHODSNinety 21-day-old male SD rats were randomly and equally divided into 4 experimental groups (Da, Db, Dc and Dd), which were injected with DES dissolved in corn oil at the dose of 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) from postnatal day (PND) 22 to 35, and a control group (C), which received vehicle only. The testicular development of all the rats was observed, and their testes were harvested in the stages of late puberty (PND 50), sexual maturity (PND 64) and adulthood (PND 130) respectively to determine the weight and histological features of the testis and examine the quality of the sperm in the epididymal cauda of the PND 130 rats.

RESULTSThe testis descent in the C, Da, Db, Dc and Dd groups occurred on PND 26.17 +/- 1.94, 26.83 +/- 1.47, 28.68 +/- 1.03, 33.50 +/- 1.87 and 41.50 +/- 2.74 respectively, significantly delayed in the Db, Dc and Dd groups compared with the C group (P < 0.05 or P < 0.01). On PND 50, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.38 +/- 0.01) g, (1.38 +/- 0.12) g, (1.30 +/- 0.14) g, (0.86 +/- 0.18) g and (0.73 +/- 0.27) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.01). Compared with the C group, there was a slight decrease in the number of the cells in the epithelia of a few seminiferous tubules in the Db group on PND 50, maldevelopment of seminiferous tubules, reduced cell number in seminiferous epithelia, blocked spermatogenesis and aplasia of Leydig cells in the Dc and Dd groups in a dose-dependent manner. On PND 64, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.60 +/- 0. 06) g, (1.62 +/- 0.11) g, (1.58 +/- 0.08) g, (1.47 +/- 0.10) g and (0.99 +/- 0.37) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.05 or P < 0.01), and the histological alteration of the testis in the Dc and Dd groups was similar to or less than that on PND 50. On PND 130, no statistic difference was observed either in unilateral testis weight or in the histological features of the testis between any experimental group and the control (P > 0.05). The sperm concentration in the epididymal cauda in the C, Da, Db, Dc and Dd groups were (73.00 +/- 16.90) x 10(6)/ml, (68.00 +/- 19.67) x 10(6)/ml, (68.67 +/- 12.15) x 10(6)/ml, (35.17 +/- 15.64) x 10(6)/ml and (19.13 +/- 5.17) x 10(6)/ml, significantly lower in the Dc and Dd groups than in the C group (P < 0.01). There was a significant decrease in sperm motility in the Dd group (P < 0.01), the percentage of grade a sperm in the Db, Dc and Dd groups (P < 0.05) and the percentage of grade b sperm in the Dd group (P < 0.01).

CONCLUSIONPrepubertal exposure to low dose of DES (0.01 microg/[kg x d] x 14 d) does not significantly affect the testicular development and function of SD rats, while high dose (1.0-10.0 microg/[kg x d] x 14 d) has significant short- (PND 50 and 64) or long-term (PND 130) toxic effect, which increases with dose and decreases with age. The mechanism of the toxic effect involves the insults to the development and function of Leydig and Sertoli cells.

Animals ; Carcinogens ; toxicity ; Diethylstilbestrol ; toxicity ; Dose-Response Relationship, Drug ; Male ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sexual Maturation ; drug effects ; Testis ; drug effects ; growth & development ; physiology ; Time Factors

AIMTo examine the expression and regulation of integral membrane protein 2b (Itm2b) in rat male reproductive tissues during sexual maturation and under different treatments by in situ hybridization.

METHODSTestis, epididymis, and vas deferens were collected on days 1-70 to examine Itm2b expression during sexual maturation. To further examine the regulation of Itm2b, adult rats underwent surgical castration and cryptorchidism. Ethylene dimethane sulfonate and busulfan treatments were carried out to test the regulation of Itm2b after destruction of Leydig cells and germ cells.

RESULTSIn testis, Itm2b expression was moderately detected in the adluminal area of seminiferous cords on days 1-10, and detected at a low level in the spermatogonia on days 20 and 30. The Itm2b level was markedly increased in Leydig cells from day 20 to day 70. In epididymis and vas deferens, Itm2b was detected from neonate to adults, and the signal gradually increased in accordance with sexual maturation. Itm2b expression was significantly downregulated in epididymis and vas deferens of castrated rats, and strongly stimulated when castrated rats were treated with testosterone. Cryptorchidism led to a significant decline of Itm2b expression in testis and caput epididymis. Itm2b expression in epididymis and vas deferens was significantly decreased after the Leydig cells were destroyed by ethylene dimethane sulfonate. Busulfan treatment produced no obvious change in Itm2b expression in epididymis or vas deferens.

CONCLUSIONOur data suggested that Itm2b expression is upregulated by testosterone and might play a role in rat male reproduction.

Animals ; Base Sequence ; Busulfan ; pharmacology ; DNA Primers ; Epididymis ; drug effects ; metabolism ; In Situ Hybridization ; Male ; Membrane Proteins ; metabolism ; Orchiectomy ; Rats ; Rats, Wistar ; Sexual Maturation ; Testis ; drug effects ; metabolism ; Vas Deferens ; drug effects ; metabolism

OBJECTIVETo preliminarily study the effect of prepubertal exposure of male SD (Sprague-Dawley) rats to diethylstilbestrol (DES) on the apoptosis of spermatogenic cells after sexual maturation and its mechanism.

METHODSThirty 21-day-old male SD rats were randomly divided into 4 experimental groups, DES 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) and 1 control group. The experimental groups were injected (s.c.) with different doses of DES (dissolved in corn oil) during prepuberty [from postnatal day (PND) 22 to PND 35] and the control group with medium only. The apoptosis and related proteins Bcl-2 and Bax expressions of testicular spermatogenic cells were studied with TUNEL and immunohistochemistry after the rats sexual maturation (at PND 64).

RESULTSCompared with the control group, the apoptosis of testicular spermatogenic cells in the DES 0.01 microg/kg group had no difference, but significantly increased in the DES 0.1, 1.0 and 10.0 microg/kg groups and the apoptosis increased with the increase of DES dose. In the control and DES 0.01 microg/kg groups, Bax protein expressed weakly but Bcl-2 protein strongly in spermatogenic cells. With the increase of DES exposure, Bax protein expression in spermatogenic cells increased but Bcl-2 protein expression decreased.

CONCLUSIONPrepubertal exposure of SD rats to inappropriate dose of DES can make the apoptosis of spermatogenic cells increase after sexual maturation. Bax and Bcl-2 proteins participate in the apoptotic course caused by prepubertal DES exposure.

Animals ; Apoptosis ; drug effects ; Diethylstilbestrol ; toxicity ; Dose-Response Relationship, Drug ; Male ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sexual Maturation ; Spermatids ; drug effects ; metabolism ; bcl-2-Associated X Protein ; biosynthesis

OBJECTIVETo evaluate the effects of neonatal exposure to different doses of bisphenol A (BPA) on the vaginal opening day (VOD), hypothalamic Kiss-1 mRNA expression, and ovarian estrogen receptor (ER) mRNA expression in female rats.

METHODSNeonatal female Sprague-Dawley (SD) rats were randomly divided into six groups: blank control, vehicle, 17β-estradiol (17β-estradiol, E2, 10 μg/d), low-dose BPA [25 μg(kg·d)], medium-dose BPA [50 μg(kg·d)], and high-dose BPA groups [250 μg(kg·d)]. The rats were subcutaneously injected with respective agents on postnatal days 0-6. The VOD was recorded, and each rat was sacrificed on the same day. The hypothalamus and ovary were taken and weighed, and the organ coefficients of hypothalamus and ovary were calculated. The hypothalamic Kiss-1 mRNA expression and ovarian ERα and ERβ mRNA expression were measured by real-time PCR.

RESULTSCompared with the control group, the E2 and medium- and high-dose BPA groups had advanced VOD, and the E2 group had significantly reduced hypothalamic Kiss-1 mRNA expression and ovarian ERβ mRNA expression (P<0.05).

CONCLUSIONSNeonatal exposure to medium- and high-dose BPA[50 and 250 μg/(kg·d)] can induce precocious puberty in rats, but it may not result from the change in hypothalamic Kiss-1 mRNA expression. Neonatal exposure to low-dose BPA [25 μg/(kg·d)] does not induce precocious puberty in rats.

Aging ; Animals ; Animals, Newborn ; Benzhydryl Compounds ; toxicity ; Dose-Response Relationship, Drug ; Female ; Hypothalamus ; drug effects ; metabolism ; Kisspeptins ; genetics ; Male ; Phenols ; toxicity ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; genetics ; Sexual Maturation ; drug effects

AIMTo assess proliferative and apoptotic potential of the seminiferous epithelium cells in relation to Sertoli cell maturation in newborn rats under the influence of estradiol, follicle stimulating hormone (FSH) or both agents given together.

METHODSFrom postnatal day (PND) 5 to 15 male rats were daily injected with 12.5 microg of 17beta-estradiol benzoate (EB) or 7.5 IU of human purified FSH (hFSH) or EB + hFSH or solvents (control). On postnatal day 16, autopsy was performed. Sertoli cell maturation/function was assessed by morphometry. Proliferation of the seminiferous epithelium cells was quantitatively evaluated using immunohistochemical labeling against proliferating cell nuclear antigen and apoptosis using the TUNEL method.

RESULTSAlthough EB inhibited Sertoli cell maturation and hFSH was not effective, a pronounced acceleration of Sertoli cell maturation occurred after EB + hFSH. Whereas hFSH stimulated Sertoli cell proliferation, EB or EB + hFSH inhibited Sertoli cell proliferation. All treatments significantly stimulated germ cell proliferation. Apoptosis of Sertoli cells increased 9-fold and germ cells 2-fold after EB, and was not affected by hFSH but was inhibited after EB + hFSH.

CONCLUSIONAt puberty, estradiol inhibits Sertoli cell maturation, increases Sertoli and germ cell apoptosis but stimulates germ cell proliferation. Estradiol in synergism with FSH, but neither of the hormones alone, accelerates Sertoli cell maturation associated with an increase in germ cell survival. Estradiol and FSH cooperate to induce seminal tubule maturation and trigger first spermatogenesis.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Estradiol ; pharmacology ; Follicle Stimulating Hormone ; pharmacology ; Male ; Rats ; Rats, Wistar ; Seminiferous Tubules ; cytology ; drug effects ; Sexual Maturation ; drug effects ; physiology ; Spermatogenesis ; drug effects ; physiology ; Spermatozoa ; cytology ; drug effects ; Testis ; cytology ; drug effects