Benjamin Thysen

The Relationship between Long-Distance Running, Plasma Progesterone, and Luteal Phase Length

The chronic effects of long-distance running upon the menstrual cycle were studied in a healthy, ovulatory 30-year-old woman. Luteal phase plasma concentrations of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and progesterone were compared during a control and a training cycle. The luteal phase was shorter in cycles of greater mileage. Mid-luteal phase plasma progesterone concentrations were significantly lower during training.

Effects of cannabinoids on reproduction and development.

Publisher Summary This chapter discusses the effects of cannabinoids on reproduction and development. The potential importance of the effects of marihuana on reproduction and development has been recognized. This recognition has led to an increasing number of studies and reports on the action of marihuana and its purified cannabinoid fractions on reproductive capacity and events and on embryonic and fetal development. Cannabinoids exert a direct inhibitory action on testicular androgen synthesis and cell metabolism. This is in contrast to the variable weight changes but explains in part the drop in plasma testosterone levels following cannabinoid intake. The addition of tetrahydrocannibinol (Δ 9 -THC) or cannabinol to mouse testes minces in incubation medium inhibited endogenous testosterone production by more than 50%. The acute administration of marihuana by smoking usually leads to a decrease in circulating testosterone and luteinizing hormone levels. The effect of cannabinoids on maternal physiology during pregnancy and lactation is also elaborated in the chapter.

Reproductive toxicity of 2,4-dinitrotoluene in the rat☆

The present study was undertaken to evaluate the effects of the chemosterilant 2,4-dinitrotoluene (DNT) on the rat testis. Adult male rats were fed control, or 0.1%, or 0.2% DNT for 3 weeks. An ultrastructural study of the testes was performed, serum was assayed for testosterone and gonadotropins, and sperm reserve count was determined. A marked change in Sertoli cell morphology was found after 3 weeks of 0.2% DNT exposure. Varying sized vesicles associated with swollen mitochondria and distended endoplasmic reticulum were visible in cells from DNT-treated animals. Circulating levels of follicle stimulating hormone and luteinizing hormone were increased in 0.2% DNT-treated animals. Reduced weights of the epididymides and decreased epididymal sperm reserves were observed in DNT-treated animals. These results indicate that DNT is capable of inducing testicular injury, of directly or indirectly disturbing pituitary function, and of exerting a toxic effect at the late stages of spermatogenesis. These findings suggest that a locus of DNT action is the Sertoli cell, resulting in both inhibition of spermatogenesis and changes in testicular-pituitary endocrine activity.

Combined treatment with radioestradiol-lucanthone in mouse C3HBA mammary adenocarcinoma and with estradiol-lucanthone in an estrogen bioassay

Abstract C3H female mice bearing transplantable estrogen-nondependent adenocarcinomas were treated subcutaneously with either estradiol, tritiated ( 3 H)estradiol, lucanthone, 3 H-estradiol followed by lucanthone, or lucanthone followed by 3 H-estradiol. Tumor growth and host survival were ascertained. As single agents, lucanthone or 3 H-estradiol had slight tutor-inhibiting effects with small tumors. Combined treatment with radioestrogen followed by htcatlthone 4 hrs later blocked early tumor growth for several days and permanently reduced the growth rate thereafter; it also lengthened survival by some 67%. On the other hand, combined treatment with lucanthone followed 1 hr later by 3 H-estradiol did not have the same effect. The increase in adrenal gland weight that occurs as this tumor grows was significantly reduced by treatment with lucanthone, and more so by 3 HE2…..+Lu; both of these treatmelnts also depressed the lymphatic system. It is suggested that the antitumor effects observed may be mediated-systemically via the adrenal. None of the treatments were effective against advanced tumors. Lucantbone was also administered subcutaneously to w female Swiss mice in conjunction with estradiol. Evidence showed that lucanthone interferes with the immature mouse uterine weight response to estrogen, especially what given 1 hr before the hormone. Although an estrogen dose-response relationship was demonstrated for all groups, the hormone and the DNA intercalating agent interfered with each other in a way that suggests possiblle steric or competitive inhibition. Thus lucanthone modulates two estrogen effects, namely, the effect of estrogen out an estrogen-response tissue (uterine weight, especially when given prior to the hormone), and the effect of radioestrogen on an estrogen-nondependent antonomous tumor (when given after the hormone). A novel antitumor strategy, here called radiocytochemotherapy , is described, and possible applications to human tumors are discussed.

Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting.

Objective: This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. Materials and Methods: Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. Results: At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. Conclusions: Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

The effect of mono(2-ethylhexyl) phthalate on Sertoli cell transferrin secretion in vitro

We have examined the effect of mono(2-ethylhexyl) phthalate (MEHP) on the secretion of rat transferrin (rTf) by Sertoli cells (SC) in the presence and absence of FSH. Significant decreases in rTf secretion were observed in SC cultures exposed to 50 and 75 microM MEHP, in the absence of FSH. Treatment of SC with FSH (300 ng/ml) obviated this suppression of rTf secretion by MEHP. These findings indicate an effect of MEHP on rTf secretion by SC in vitro which could account for the testicular toxicity of MEHP in vivo.

Endogenous Estradiol and Progesterone Concentrations in Smokers on Oral Contraceptives

The simultaneous effects of cigarette smoking and oral contraceptives on serum estradiol and progesterone levels were investigated in 114 premenopausal women. Serum 17 beta-estradiol and progesterone levels were measured by radioimmunoassay. In smokers, estradiol and progesterone levels were significantly lower (p less than 0.025). In smokers using oral contraceptives, estradiol and progesterone levels were the lowest (p less than 0.001 and p less than 0.01, respectively). The findings suggest that smoking and oral contraceptives independently lower serum estradiol and progesterone concentrations in premenopausal women and that the effects may be additive.

Reproductive toxicity of 2,4-toluenediamine in the rat. 1. Effect on male fertility

Effects of 2,4-toluenediamine (TDA) on reproduction in adult male Sprague-Dawley rats were evaluated. Diets containing 0, 0.01 and 0.03% TDA were fed ad libitum to experimental animals for 10 wk. No signs of toxicity were found. Exposure to the high dose resulted in decreased mating frequency and an increase in infertile matings. Light-microscopic examination of the testes revealed reduced numbers of sperm in the seminiferous tubules and cauda epididymides. These results indicate that TDA is capable of reducing fertility and of exerting an inhibitory or toxic effect on spermatogenesis in the rat.

Reproductive toxicity of 2,4‐toluenediamine in the rat. 2. Spermatogenic and hormonal effects

The present study was undertaken to evaluate the endocrinologic and spermatogenic effects of 2,4-toluenediamine (TDA) in the rat. Adult male rats were fed 0,0.01, and 0.03% TDA ad libitum for 10 wk. At the end of wk 10 and at 11 wk post TDA treatment, the animals were killed, and cauda epididymal sperm counts and reproductive organ weights were determined. Blood samples were obtained for analyses of testosterone and gonadotropins. Treatment with 0.03% TDA for 10 wk reduced the weight of the seminal vesicles and epididymides and reduced serum testosterone levels. Cauda epididymal sperm counts were decreased in animals treated with 0.03% TDA for 10 wk and in TDA-treated animals placed on normal diet for 11 wk. Serum luteinizing hormone (LH) concentrations were increased and weights of epididymides and testes were reduced in 0.03%-TDA-treated animals placed on normal diet for 11 wk. The results indicate that TDA exerts a toxic effect on spermatogenesis and appears to affect androgen action and production in the male rat. Since the males exhibited reduced cauda epididymal sperm counts 11 wk after 0.03% TDA treatment, it appears that TDA induced damage to the germinal components of the testes.

Reproductive toxicity of 2,4‐toluenediamine in the rat. 3. Effects on androgen‐binding protein levels, selected seminiferous tubule characteristics, and spermatogenesis

In previous studies we demonstrated reduced fertility, arrested spermatogenesis, and diminished circulating testosterone levels in rats fed 0.03% 2,4-toluenediamine (TDA) for 10 wk. These studies were extended in three experiments by determining TDA effects on androgen-binding protein (rABP) production and on seminiferous tubule structure, and on early changes in testes morphology and spermatogenesis. In the first experiment, rats fed 0.03% TDA for 10 wk showed a 7- to 9-fold increase in rABP content in testicular cytosol or in media of cultured seminiferous tubules, a 4-fold increase in serum rABP, but a two-thirds decrease in epididymal rABP levels. Testes examination by transmission electron microscopy revealed degenerative changes in Sertoli cells with, where present, normal spermatocytes and spermatids. In the second experiment, 0.03% TDA fed for 4, 6, or 8 wk resulted in a doubling of testes/body weight ratios and a highly correlated 2.5- to 2.9-fold increase in seminiferous tubule fluid volume. An approximately 50% decrease in epididymal sperm reserves was found after 6 or 8 wk of TDA exposure. After 10 wk of exposure to 0.03% TDA, testicular weight was the same as in control-fed rats but seminiferous tubule fluid volume was still elevated. These changes in testicular characteristics indicate TDA effects on Sertoli cell function, on RABP release from the testes (and epididymides), and possibly on tubular fluid transport. In the third experiment, rats fed 0.06% TDA for 1 wk showed a 25% decrease in epididymal sperm content, reduced epididymal weight, and minor structural changes in Sertoli cells. After 3 wk of 0.06% TDA feeding, sperm counts were further reduced, and were accompanied by a dramatic increase in testes weight, intense fluid accumulation, and ultrastructural changes in Sertoli cells. No significant changes in serum testosterone levels were noted in the TDA-treated rats. The results of this third experiment demonstrate TDA toxicity on testicular spermatogenesis within 3 wk of TDA feeding. The within 3 wk of TDA feeding. The findings in this study suggest that the early inhibition of spermatogenesis by TDA is mediated through Sertoli cell damage.