Virilizing effect of testosterone and its metabolites on the urovaginal septum of female fetal rats

A single injection of 50 microgram testosterone was given to fetal rats on day 17, 18, 19 or 20 of gestation. On day 21, the fetuses were removed from the mother under maternal ether anesthesia, and the length of the urovaginal septum was measured microscopically in female fetuses in order to assess the virilizing effect of testosterone. In fetuses treated with testosterone on day 17, the length of the urovaginal septum was comparable to that of oil-treated littermate controls. In fetuses treated on day 18, the length was significantly abridged compared with controls. In fetuses treated on day 19, the abridgment of the urovaginal septum was most marked. In fetuses treated on day 20, the length of the septum was again comparable to that of controls. The observations suggest that day 19 is the critical day for the virilizing effect of testosterone. Various amounts of testosterone and its metabolites including dihydrotestosterone, androstane-3 beta, 17beta-diol and androstane-3 alpha, 17beta-diol were injected into 19-day-old female fetuses, in order to test the dose relation to the virilizing effects of these steroids in terms of abridgment of the urovaginal septum. As a consequence, it was found that testosterone was the most effective for virilization.     

Virilizing activities of various steroids in female rat fetuses

Virilizing activities of nineteen steroids were examined by a method measuring the abridgment of urovaginal septum length of female rat fetuses directly under microscope, following oral administration of the steroids to the mothers for 4 days during the late period of gestation. The characteristics of the virilizing activities of the steroids seemed to depend on their chemical structures. No virilizing activities were observed in progesterone, retroprogesterone, chlormadinone acetate and nandrolone phenpropionate. The introduction of 6-methyl and 17-acetoxy groups into progesterone exhibited a marked virilizing activity. With testosterone and its derivatives, the introduction of 17alpha-ethynyl group into testosterone slightly decreased the virilizing activity compared with the parent compound. On the contrary, the introduction of [3, 2-C] pyrazole ring in addition to the saturation of A-ring strikingly increased the virilizing activity. The most active virilizing steroid in this group was stanozolol followed by oxymetholone, methyl-testosterone and dimethysterone. Testosterone propionate was assumed to be less active than methyltestosterone by this route. With 19-nortestosterone derivatives, the virilizing activities of compounds with 17alpha-ethynyl group were moderate, but the presence of 17alpha-ethyl group caused a marked increase of virilizing activity. While, nandrolone phenpropionate with long side chain at C-17 exhibited no significant virilizing activity. The present results show the possibility of the evaluation on a potential virilizing activity of compounds in the female fetus, and also suggest that a dossociation between the virilizing activity and the androgenic activity may exist among some compounds.     

Virilizing effect of methyltestosterone on female descendants in the rat

Pregnant rats were given daily a subcutaneous injection of methyltestosterone for 4 days from the 17th to the 20th day of gestation, and were allowed to be delivered to their offsprings (F1) which were used for the examination of later reproductive functioning. When observed for 21 weeks after birth, the growth rate of F1 from methyltestosterone-treated groups was higher than that of F1 from the control group. The anogenital distance in 50-microgram-treated F1 females started to become significantly longer on the 14th day and in 5-microgram-treated F1 females on the 28th day after birth than that in F1 from the control. The day on which vaginal opening took place in 50% of females was 34.4 days of age in both the control and the 5 microgram groups, but it delayed until 40.7 days in the 50 microgram group. Furthermore, persistent estrus was observed after about 90 days of age in the 50 microgram group. This persistent estrus disappeared by placing these females with males, resulting no pregnancy. In the 5 microgram group females could be pregnant, but their female fetuses (F2), when examined on the 21st day of gestation, had significantly shortened the length of the urovaginal septum. The observations show that virilization can be induced in the third generation.     

Paradoxical effects of maternal stress on fetal steroids and postnatal reproductive traits in female mice from different intrauterine positions

We examined effects of maternal stress on prenatal serum concentrations of testosterone and estradiol and on postnatal reproductive traits in female mice from different intrauterine positions. On Day 18 of fetal life, control females positioned in utero between two male fetuses (2M females) had higher concentrations of testosterone and lower concentrations of estradiol in serum than control female fetuses located between two females (0M females). Control females positioned between a male and a female fetus (1M females) had intermediate levels of both hormones. Prior intrauterine position in control females accounted for differences in genital morphology (length of the anogenital separation) at birth and length of estrous cycles during adulthood. Maternal stress eliminated these postnatal differences due to prior intrauterine position: all 0M, 1M, and 2M female offspring of stressed mothers exhibited postnatal traits that were indistinguishable from those of control 2M females. Maternal stress resulted in an increase of over 1 ng/ml in serum testosterone in all female fetuses; the magnitude of the increase was similar for 0M, 1M, and 2M females. There was no effect of maternal stress on serum concentrations of estradiol in 0M and 2M female fetuses. Maternal stress resulted in a dramatic change in the postnatal traits of 0M females, whereas 2M females showed no change. Since the effect of maternal stress on sex steroids was similar among fetuses from different intrauterine positions but postnatal response to maternal stress varied by intrauterine position, other components of the endocrine system may mediate effects of maternal stress on these postnatal characteristics.     

Development of the external genitalia in fetuses of the southern minke whale, Balaenoptera acutorostrata

The developmental changes of the anogenital distance and external genitalia were studied in 81 fetuses of the southern minke whale. It was difficult to sex the fetuses with less than 55.8 mm crown-rump length (CRL) even by histological means, but it was easy in the fetuses with more than 77.0 mm CRL and less than 110.0 mm CRL. The histologically determined male fetuses had a ratio of anogenital distance to CRL or body length of more than 5%, while females had a value of less than 4%. At later stages with a CRL of more than 113.0 mm, male fetuses had an umbilicus-directed genital tubercle, while in females a tail-directed tubercle was observed. The present study suggests that the stage with sexual dimorphism might be earlier in the southern minke whale than that previously reported.     

Perinatal exposure to 19-Nor-17α-ethynyltestosterone (norethindrone) influences morphology and aggressive behavior of female mice

Pregnant mice were injected with 50 or 100 μg of the synthetic progestin 19-nor-17α-ethynyltestosterone (NET) on Days 14 through 17 of gestation. Others received only the vehicle or were left undisturbed. Exposure to NET during the prenatal period increased anogenital distance of the female offspring as measured on Day 60 but did not influence the duration of adult testosterone (T) exposure required to activate male-like intraspecific fighting behavior. In a second experiment, female mice were exposed to NET either prenatally, postnatally (Day 1), or pre- and postnatally. Exposure during both pre- and postnatal periods increased anogenital distance but only the exposure during the postnatal period enhanced later behavioral sensitivity to the aggression-activating property of T. Thus, NET is similar to testosterone in its ability to virilize morphology and behavior, although, at the dosages administered, behavioral alternation only occurred as a result of treatment during the neonatal period.     

Chronic administration of anabolic steroids disrupts pubertal onset and estrous cyclicity in rats

Use of anabolic-androgenic steroids (AASs) is becoming increasingly popular among adolescent girls, yet the effects of AASs on female physiology and development are not well understood. The present study compared the effects of chronic exposure to three individual AASs, stanozolol (0.05-5 mg/kg), 17alpha-methyltestosterone (0.5-5 mg/kg), and methandrostenolone (0.5-5 mg/kg) on the onset of puberty and estrous cyclicity in the rat. Female rats received daily injections of AASs for 30 days (Postnatal Day [PN] 21-51). Rats receiving the highest dose of each of the AASs (5 mg/kg) displayed vaginal opening at a younger age than rats receiving the oil vehicle. The day of first vaginal estrus was delayed in rats receiving stanozolol (5 mg/kg) or 17alpha-methyltestosterone (0.5-5 mg/kg) but not in rats receiving methandrostenolone. At the highest dose (5 mg/kg), each of the AASs reduced the incidence of regular estrous cyclicity during the treatment period. Concurrent administration (on PN21-51) of the androgen receptor antagonist, flutamide (10 mg/kg, twice daily), reversed the effects of 17alpha-methyltestosterone (5 mg/kg) on vaginal opening. Flutamide administration also eliminated the effects of stanozolol (5 mg/kg) and 17alpha-methyltestosterone (5 mg/kg) on the day of first vaginal estrus. In contrast, rats receiving flutamide and methandrostenolone (5 mg/kg) exhibited first vaginal estrus earlier than controls. The present results indicate that chronic exposure to AASs during development has deleterious effects on the female neuroendocrine axis and that these effects appear be mediated via multiple mechanisms.     

Ontogeny of secretory patterns of LH release and effects of gonadectomy in the chronically catheterized pig fetus and neonate

Two experiments were conducted to determine the ontogeny of secretory patterns of luteinizing hormone (LH) release and effects of gonadectomy on the characteristics of LH secretion in the chronically catheterized pig fetus and neonate. To study secretory patterns in intact animals, blood samples were collected from 44 pig fetuses and their mothers (Days 81, 99, 109 and 113 of gestation) as well as from 25 neonates (Days 4 and 8) every 15 min for 3 h (2 h on Day 81). The results indicate that the fetal adenohypophysis secretes occasional pulses of LH as early as Day 81 of fetal life. Fetal and maternal mean LH levels are low (0.25-0.50 ng/ml) at all gestational ages, with lowest values just before birth (Day 113 post coitum). Four-day-old neonates show a significant increase in pulse frequency (male and female) as well as pulse amplitude (female), relative to fetal values, leading to significant augmentations in mean LH levels. This is associated with reductions in both 17 beta-estradiol and progesterone. By 8 days of age significant sex differences in mean LH levels (males greater than females) appear. Testosterone/5 alpha-dihydrotestosterone levels (males) are low prenatally but are significantly increased after birth, possibly due to the stimulating effects of increasing LH levels. To study the gonadal control of LH secretion, forty-one 105-day-old fetuses and thirty-eight 4-day-old neonates were chronically catheterized and were either gonadectomized or remained as sham or control animals. Forty-eight and 96 h after surgery, blood samples were taken every 15 min for 3 h. No significant changes are detectable at 96 h in mean LH, pulse frequency and amplitude in female or male fetuses or in neonates. While significant reductions in testosterone levels are observed at 96 h in the male fetus and neonate, progesterone concentration is reduced only in the neonate. In the castrated female, on the other hand, neither fetus nor neonate display significant changes in circulating levels of progesterone and 17 beta-estradiol at 96 h. It is concluded that the pituitary of the pig is able to discharge LH with occasional pulses as early as Day 81 of fetal life; however, the pituitary remains suppressed until after birth, probably due to high circulating nongonadal steroids in the fetal compartment.     

Utility of maternal serum total testosterone analysis for fetal gender determination in Asian elephants (Elephas maximus).

It has been shown in some species that fetal testes produce testosterone early in gestation. This study investigated the possibility that fetal testosterone may be reflected in maternal serum levels in the Asian elephant (Elephas maximus). Weekly serum samples were collected from seventeen pregnant captive Asian elephants and analyzed via radioimmunoassay (RIA) for total testosterone levels. Nine of the cows carried male fetuses and eight carried female fetuses. A non-random pattern over time (P<0.01) was observed in cows carrying either a male or female fetus. Mean maternal serum total testosterone was significantly higher in cows carrying male versus female fetuses (P<0.01). Mean trimester values indicate that first trimester values are not significantly different among male versus female groups. The second and third trimester values of cows carrying male fetuses were higher than cows carrying female fetuses, (P<0.01 and <0.05, respectively). The results of this study show that it is possible via RIA of maternal serum for total testosterone to determine the gender of calves during gestation.     

Plasma corticosteroid patterns in the fetus

In umbilical vein blood samples collected in 137 fetuses between 19 and 31 weeks of gestation, cortisol (F), cortisone (E), 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) were radioimmunoassayed after column chromatography on Sephadex LH-20 of plasma extracts. While F levels plateaued throughout the period considered those of E displayed an increasing pattern which appeared to be comparable with that of unbound F in pregnant women. The declining pattern of S and more particularly of 17-OHP would suggest an increasing utilization and metabolization of these F precursors by the maturing fetus. E was not correlated with either 17-OHP or S but showed a significant correlation with F. S and 17-OHP were correlated with each other and with F. The significance of these correlations was discussed according to the different origin of these steroids and to their metabolic relationships. The application of this method for the prenatal diagnosis of inborn errors of steroid biogenesis is suggested.     

Prostaglandin production by porcine allantochorion in vitro: effect of cortisol infusion in vivo.

The effect of cortisol infusion into the porcine fetus on subsequent prostaglandin (PG) production in vitro by the fetal placenta (the allantochorion) was studied. Also, the possible in vitro effects of glucocorticoids and other steroids on PG production by dispersed cells were examined. Two fetuses in each of 6 sows were catheterized on day 100 or 101 of gestation (normal gestation is 114-116 days); one was infused with cortisol (6 mg/day) and one with saline for 5 days beginning on day 103. On day 108, fetal allantochorionic tissue was aseptically collected from the infused fetuses and 2 uninfused litter mates (controls). Pieces of tissues were cut from the allantochorion (4 sows) and dispersed cell preparations were made from each fetus (4 sows). Each preparation was cultured for 24 h, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha (prostacyclin metabolite) measured. In vivo cortisol infusion had no significant effect on the in vitro production of PGE2 or PGF2 alpha by tissues or dispersed cell preparations. However, tissue from the fetuses infused with cortisol produced significantly less 6-keto-PGF1 alpha than uninfused controls (54% of control, p < 0.05). The dispersed cells from uninfused fetuses and 2 cortisol-infused animals were also incubated for 24 h with 10(-7) and 10(-9) M concentrations of estrone, estradiol, progesterone, cortisol, and dexamethasone, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha was measured. No significant effect of any of these steroids in vitro on prostanoid production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age at puberty, ovulation rate, uterine length, prenatal survival and litter size in Chinese Meishan and Yorkshire females

Studies on the ovulation rate, prenatal survival and litter size of Chinese Meishan pigs have given widely divergent results depending on the extent of inbreeding of the animals, their original genetic diversity, the age and parity, and the conditions of management. To obtain meaningful results, it is necessary to characterize the population under study. The following report characterizes populations of Meishan and Yorkshire of a widely diverse background. First farrowing data were collected on 21 Meishan and 20 Yorkshire gilts. Meishan gilts had 12.4 fully formed piglets and Yorkshire gilts had 7.4 fully formed piglets (P < 0.01). Meishan gilts averaged 1.86 mummified fetuses per litter vs 0.05 per Yorkshire litter (P < 0.01). Yorkshire piglets averaged 1.3 kg body weight at birth vs 0.9 kg for Meishan piglets (P < 0.01). At 47 days of second gestation, 19 Meishan and 12 Yorkshire sows averaged 22.7 and 16.3 corpora lutea (CL), respectively (P < 0.01). Uterine length and number of fetuses were not different (P > 0.40) in the two breeds. Daily estrous detection of 50 Meishan and 34 Yorkshire gilts began at 60 and 120 days of age, respectively. Meishan gilts reached sexual maturity at 95 days of age, which was 105 days earlier than Yorkshire gilts (P < 0.01). Meishan gilts were in estrus nearly 1 day longer than Yorkshire gilts at first, second and third estrus (P < 0.05). No differences in cycle length between breeds were detected for the first or second estrous cycle (P > 0.60). Nineteen Meishan gilts were slaughtered at 51 days of gestation and their reproductive tracts were recovered. The mean number of dissected CL (17.0), number of fetuses (13.1), total uterine length (396 cm), spacing per fetus (29.9 cm), allantoic (124.9 ml) and amniotic (32.2 ml) volumes, crown-rump length (82.8 mm), weight (35.4 g), sex, and direction of each fetus were determined. Chinese Meishan gilts reached puberty much earlier and were in estrus longer than Yorkshire gilts and Meishan sows had more CL than Yorkshire sows.     

Compared action of norethindrone and various steroids on Müller ducts of the female chick embryo]

Treatment of female chick embryo with norethindrone (NET), a potent progesterone-like steroid, caused caudal agenesia and cephalic regression of Mullerian ducts as the normal regression induced by anti-Mullerian-hormone in the male embryo. The comparative study of five other progesterone-like steroids shows that only lynestrenol which is metabolized into NET at least in man, possesses the same properties as NET. The four others, i.e. medroxyprogesterone, medrogestone, norgestrienone and 17 alpha hydroxyprogesterone are only able to induce agenesia, an unspecific property, which was observed with many steroidal hormones, as norethandrolone here studied.     

Enzyme induction in Streptomyces hydrogenans. V. Characterization of testosterone-17 beta-dehydrogenase and its induction by steroids]

Testosterone 17beta-dehydrogenase can be enriched from Streptomyces hydrogenans. The enzyme dehydrogenizes testosterone with Km=13muM and estradiol-17beta with Km=21muM to the corresponding 17-ketoderivatives. NAD forms NADH with Km=125muM. The enzyme is strongly inhibited by androstandione and 17alpha-methyltestosterone. The Ki for 17alpha-methyltestosterone is 18muM. The enzyme activity increases with increasing pH up to alkali-mediated denaturation at about pH 10. The optimum temperature is at 45 degrees C. If Streptomyces hydrogenans is cultivated in the absence of steroids, the specific activity of testosterone 17beta-dehydrogenase in the cytosol of the microorganisms amounts to 10 mU/mg protein, and increases up to 10-fold if the cells are cultivated in the presence of certain steroids. Testosterone, alpha-dihydrotestosterone, beta-dihydrotestosterone, estradiol-17beta, and 17alpha-methyltestosterone are very effective inducers. Thus, for the first time, the ability of estradiol-17beta to induce an enzyme synthesis in a microorganism is shown. The steroid-dependent induction is inhibited by testosterone acetate and rifamycin SV. Cyproterone, however, does not decrease the testosterone-dependent enzyme induction of testosterone 17beta-dehydrogenase.     

Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.     

Studies on anabolic steroids. 9. Tertiary sulfates of anabolic 17 alpha-methyl steroids: synthesis and rearrangement.

A simple and convenient method has been developed to prepare sulfates of anabolic 17 beta-hydroxy-17 alpha-methyl steroids. The sulfates of methandienone, 17 alpha-methyltestosterone, mestanolone, oxandrolone, and stanozolol were prepared. Different A-ring functions were not affected under the sulfation condition. The buffered hydrolyses of these sulfates provided the 17-epimers of the original steroids and 17,17-dimethyl-18-nor-13(14)-ene steroids, presumably via the 17-carbocations.     

Relationship of length of uterus in prepubertal pigs and number of corpora lutea and fetuses at 30 days of gestation

Relationships of the length of the uterus at one reproductive stage to the length at other stages and the effect on potential litter size were determined. In Experiment 1, the length of the uterus was measured in situ at 20, 60, or 100 days of age at laparotomy with 20 gilts in each of the three age groups. Forty days after the initial measurement, the uterus was again measured in situ, gilts were ovariectomized and hysterectomized, and associations among uterine measurements at the two different stages were determined. Correlations between uterine length in situ and between uterine length and weight 40 days later were all greater than 0.75 (P < 0.001). The length of one uterine horn increased from 13.9 cm at 20 days of age to 36.7 cm at 140 days of age (P < 0.01). In Experiment 2, 66 gilts were unilaterally hysterectomized and ovariectomized (UHOX) at 150 days of age and the ovary was weighed. Length of the one horn was measured in 36 gilts. At 10 days after first estrus, the length of the remaining uterine horn was measured at laparotomy and corpora lutea were counted in 53 gilts. In 15 of the 53 gilts the remaining uterine horn was removed to obtain uterine weights. At the second or third estrus, 38 gilts were mated and at Day 30 of gestation, 31 gilts were pregnant. The gilts were killed, and the length of the uterus measured and corpora lutea (CL) and fetuses were counted. The length of one uterine horn at 150 days of age was 70 cm with a range of 47–110 cm. At 10 days after first estrus, length had increased to a mean of 141 cm with a range of 86–194 cm and at 30 days of gestation the mean was 244 cm with a range of 186–311 cm. There were 12.2 CL at first estrus, which was not different from 12.4 CL at the second or third estrus. The mean number of fetuses in one horn at 30 days of gestation was 9.5 with 77% prenatal survival. Length of uterine horn at 150 days of age was correlated with uterine horn length (r = 0.56, P < 0.001) at 10 days after first estrus and number of live fetuses (r=0.39, P<0.05) at 30 days of gestation. At Day 10 after first estrus, uterine length was not correlated with the number of CL, whereas at Day 30 of gestation, the number of CL and uterine length were correlated with the number of live fetuses in those gilts with below the mean number of live fetuses, but not in those gilts with above the mean of live fetuses. The number of live fetuses (r=0.66, P < 0.001) and fetal survival (r=0.63; P < 0.001) were correlated with uterine horn length in pregnant UHOX gilts. Length of the prepubertal uterus gives an indication of postpubertal length and the potential litter size in pigs.     

Lack of dominant lethality in mice following 1-bromopropane treatment

1-Bromopropane (1-BP) is widely used in spray adhesives, precision cleaner, and degreaser. This study was conducted to investigate the potential of 1-BP to induce dominant lethality in mice. 1-BP was orally administered to males at doses of 300 and 600 mg/kg for 10 days before mating. Cyclophosphamide was used as a positive control (PC), which was administered intraperitoneally to males at 40 mg/kg for 5 days. The vehicle control (VC) group received corn oil only. Thereafter, males were mated with untreated females during six sequential mating periods of a week each. Males were sacrificed at the end of mating and so were the pregnant females on days 15-17 of gestation. Clinical signs, gross findings, mating index, gestation index, the numbers of corpora lutea, implantations, live fetuses, resorptions and dead fetuses, pre- and post-implantation losses, and dominant lethal mutation rate were examined. There were no treatment-related changes in clinical signs, gross findings, mating index, gestation index, number of corpora lutea and implantations, pre-implantation loss, live fetuses, resorptions, dead fetuses, post-implantation loss at any 1-BP doses tested. In the PC group, there were no treatment-related changes in mating index, gestation index, number of corpora lutea, and dead fetuses. However, a decrease in the number of implantations and an increase in pre-implantation loss were observed during the first 2 weeks as compared to those of the VC group. No treatment-related changes were observed in the third to sixth weeks. Increases in resorptions, fetal deaths and post-implantation loss, and a decrease in the number of live fetuses were observed in the first 3 weeks of the PC group compared to those of the VC group. However, no treatment-related changes were observed during the forth to sixth weeks. An increase in dominant lethal mutation rate was observed in 1-3 weeks of mating of the PC group, but there was no significant difference in 1-6 weeks of mating of the 1-BP treatment groups. In conclusion, 1-BP did not induce dominant lethality in mice. These results are in agreement with the report of Saito-Suzuki et al., demonstrating that no dominant lethality of 1-BP was observed in Sprague-Dawley rats.     

Effects of exogenous steroids on androgen receptors in fetal guinea pig brain

We treated pregnant guinea pigs on Day 50 of gestation with 10 mg testosterone propionate (TP), obtaining fetuses 2, 4, 8, or 18 h later as well as after 5 days of treatment. In a second group of pregnant guinea pigs, dihydrotestosterone propionate (DHTP), estradiol benzoate (E2B), progesterone (P), or cortisol was given 2 h before obtaining fetuses. Although TP treatment elevated fetal serum T (p less than 0.05), brain cytosolic androgen receptor (ARc) content was unchanged in fetuses of either sex. In female fetuses, nuclear androgen receptors (ARn) increased 10-fold in medial-basal hypothalamus (MBH) and preoptic area (POA) at 2 and 4 h (respectively) after treatment, while fetal male ARn content was unchanged. Maternal injection of other steroids (E2B, P, or cortisol, but not DHTP) significantly increased these hormones in the fetus 2 h later (p less than 0.05). Only androgens affected fetal androgen receptor (AR) content. While TP increased ARn in female MBH, DHTP decreased ARc in fetal anterior pituitary of both sexes. In this latter case, a metabolite of DHT may mediate the effects. We conclude that T crosses the guinea pig placenta and activates ARn in POA and MBH of female fetuses; male ARn appear to be maximally occupied by endogenous T. Steroids of other classes do not induce AR responses in fetal guinea pig brain. These AR changes may represent an initial cellular mechanism in brain sexual differentiation.     

Relationship between the appearance of preantral follicles in the fetal ovary of Antarctic minke whales (Balaenoptera bonaerensis) and hormone concentrations in the fetal heart, umbilical cord and maternal blood

The present study aimed to determine the relationship among changes in the number of preantral follicles and concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P4), androstenedione (A) and estradiol-17beta (E2) in the fetal heart, umbilical cord and maternal blood. Primordial follicles had already appeared in a 20 cm fetus and primary follicles were observed in a 50 cm fetus. In a 70 cm fetus, the number of primordial and primary follicles increased rapidly and secondary follicles were present. The concentrations of LH and FSH did not change between 20 cm and 160 cm in fetal length. When the fetal length became > 70 cm, serum levels in the fetus, umbilical cord and mothers, and E2 levels in umbilical cord increased synchronously (p < 0.05). These results showed increases in the number of preantral follicles in the Antarctic minke whale fetal ovary along with fetal growth during the early gestation period. These findings suggest that the change in preantral follicles was associated with changes in the concentration of steroids in early gestation periods. The changes in steroid concentrations in the fetal and umbilical cord blood and the increased number of preantral follicles were coincident at around 70 cm in fetal length, whereas the growth and differentiation of primordial and primary follicles appeared to be independent of FSH and LH.