Pre- and postimplantation embryotoxic effects of zinc dimethyldithiocarbamate (Ziram) in the rat

Zinc dimethyldithiocarbamate (Ziram) was administered to pregnant CD rats by tube during the first 5 days of pregnancy (preimplantation study, 0, 25, 50, and 100 mg/kg) or during the organogenetic period (teratogenic study, 0, 12.5, 25, 50, and 100 mg/kg). All females were sacrificed on Day 21 of gestation. Their reproductive status was recorded and live fetuses were examined for external, visceral, and skeletal malformations. In the preimplantation study the only observed embryotoxic effect was a reduced fetal weight at 50 and 100 mg/kg dose level. The teratogenic study revealed a slight dismorphogenic effect of Ziram at 100 mg/kg; embryofetotoxic effects appeared at 25 mg/kg dose level and higher. Maternal toxicity was evident at all tested doses.     

米非司酮抗着床作用的实验研究

抗孕激素米非司酮皮下注射给药,对大白鼠抗着床作用随剂量增加而增强,妊娠第一天单次给药半数有效量DE_(50)为5mg/kg,完全抗着床剂量为10mg/kg,同一剂量分次给药其抗着床效果优于单次给药。     

Effect of intrauterine administration of antiprostaglandin drugs on implantation in the rat

Three antiprostaglandin drugs, acetylsalicylic acid, indomethacin and ibuprofen, were administered intraluminally at different doses to pregnant rats on Day 4 of pregnancy. It was observed that ibuprofen administered at a dose of 400 micrograms inhibited implantation in all rats. Ibuprofen when administered at a lower dose of 100 or 200 micrograms on Day 4 of pregnancy or at a dose of 400 micrograms on Day 3 or 5 of pregnancy did not exert such an antiimplantation effect. Acetylsalicylic acid and indomethacin also induced, but to a lesser extent, an antiimplantation effect when administered at a dose of 400 micrograms on Day 4 of pregnancy.     

Anordiol produces pregnancy loss in the rat--via the embryo or via the uterus?

Anordiol, the dihydroxylated metabolite of anordrin, is an antiestrogen with estrogenic activity that is known to inhibit fertility. The following study was conducted to determine the mechanism of this antifertility effect. Anordiol was administered orally to rats, prior to implantation, on Day 2 of pregnancy. Control animals were treated with the vehicle only. The effectiveness of the agent in terminating pregnancy was determined on Day 14 of pregnancy. Anordiol was 100% effective in abolishing pregnancy at a dose of 0.6 mg/Kg. Administration of smaller doses resulted in a decreased number of implanting embryos, in a dose-dependent manner. An additional dose of anordiol on Day 3 of pregnancy yielded similar results. To determine whether pregnancy impairment by anordiol is exerted via the embryo or via the uterus, reciprocal embryo transfers were performed. Day 5 blastocysts were transferred into the uteri of pseudopregnant rats. In one set of experiments, the donor rats were treated with anordiol, and in the second set the recipient rats were treated. The results indicate that the effects of anordiol administration are exerted via the embryo as well as the uterus.     

Efficacy of various locally applied chemicals as contragestational agents in rats.

Test agents were selected because of previous evidence of contragestationaal activity when administered systemically or because of known local effects which would be likely to cause endometrial changes having an adverse effect on pregnancy. A group of virgin female Sprague-Dawley rats were treated on Day 3 of pregnancy (preimplantation) and another group on Day 7 of pregnancy (postimplantation). Injections of .05 ml were made directly into the lumen of each uterine horn. Sodium chloride .9% was used on 1 side and the test agent on the other side. Implantation sites were counted before injections on Day 7. The number of corpora lutea indicated the expected number of conceptions of those injected on Day 3. On Day 15 rats were sacrificed and corpora lutea, viable conceptuses, and absorption sites were counted. Ethanol at 100, 80, 70, and 63% was a highly effective contragestational agent when given on Day 3. Formaldehyde 7-.5% was also highly effective when given on Day 3 but higher concentrations produced maternal toxicity and death. Silver nitrate, iodine, rivanol, cyclizine, urea, and 17beta-bromoacetoxy-19-nortestosterone produced no maternal toxicity but were all effective in reducing the number of viable fetuses. Prostaglandin (PGF2alpha), indomethacin, and ergonovine had no observable effect on preimplantation embryos. Methotrexate reduced survival when injected on Day 3 and more so when given on Day 7 but a systemic toxic effect was also noted. When injected on Day 7 all of the compounds except methotrexate were markedly less effective. Survival of fetuses in the control horns varied from 50% to 100%. Ethanol produced sloughing and necrosis but the endometrium appeared to be normal after 96 hours. Fecundity had not returned after 4-5 estrous cycles. The other compounds produced no histologically evident long-lasting effects. Superficial endometrial damage seemed to be the mechanism of action of compounds that were effective on Day 3. The discrepancies noted between results obtained and the documented efficiency of PGF2alpha and of urea as abortifacients in humans raises the question of the suitability of the rat as a model for predicting abortifacient activity in humans. However, the action of these 2 substances may be different in later gestational phases.     

Pregnancy and lactation modulate maternal splenic growth and development of the erythroid lineage in the rat and mouse

Maternal physiology changes dramatically during the course of gestation and lactation to meet the needs of the developing fetus and newborn. In the present study, we examined the influence of pregnancy and lactation on growth and erythroid gene expression patterns of the maternal spleen. Holtzman Sprague-Dawley rats and CD-1 mice were killed at various stages of gestation and post partum. We observed pregnancy dependent increases in spleen weight and spleen DNA content in both the rat and mouse. In the rat, spleen size was greatest at the end of pregnancy and regressed post partum. In contrast, mouse spleen size peaked by gestational Day 13 and regressed to its non-pregnant weight before parturition. Pregnancy dependent changes in the size of the spleen were primarily due to an increase in red pulp. Maternal spleen expression of erythroid-associated genes (erythroid Krüppel-like factor, erythroid 5-aminolevulinate synthase-2, beta-major globin) was influenced by pregnancy and lactation. A pregnancy dependent increase in erythroid progenitors was also observed. In summary, the demands of pregnancy and lactation cause marked adaptations in the maternal spleen. The maternal spleen increases in size and exhibits an expansion of the erythroid lineage.     

Blastocidal and contraceptive actions by an extract and compounds from endod (Phytolacca dodecandra)

An extract consisting primarily of the saponins derived from the Endod plant (Phytolacca dodecandra), three purified trisaccharides derived from the extract, and a synthetic disaccharide were tested for antifertility activity on Days 1, 4, and 6 of pregnancy. Known quantities of the crude extract or purified compounds were injected into one of the two uterine horns of rats, and the contralateral horn served as a control. Separate control groups received physiological saline in one of the two horns. Vaginal smears were routinely observed each morning, and the presence of vaginal sperm determined Day 1 of pregnancy. Then, intrauterine injections were performed by surgery on Days 1, 4, and 6 of pregnancy. Treatment with proper dose levels of the crude saponin extract, lemmatoxin, and oleanoglycotoxin-A was found to be capable of preventing pregnancy or reducing the embryonic count on all three days. Lemmatoxin-C-C' was also tested on Day 1 and found effective at proper dose levels. On Days 1 and 4, oleanolic acid cellobioside had little or no effect on pregnancy when injected in utero at doses up to 1,000 μg. Endod extract caused substantially lower decreases in surface tension of water than Nonoxynol-9, yet showed 5 to 10 times the antifertility activity when administered on Day 1. To test whether a substance acted on the uterine horn to prevent implantation, Endod extract was injected on Day 1 into one of two uterine horns at a high level, sufficient to prevent pregnancy on the treated side. When the oviducts were flushed the third day after mating, 4 out of 5 rats had embryos on the treated side which were in similar stages of development as on the untreated side. Under the conditions of these experiments, there was no obvious damage to the uterine endometrium observed histologically due to treatment with purified compounds. It is suggested that this or related classes of compounds may be useful as abortifacients during early stages of pregnancy.     

Uptake and distribution of Cd in the ovaries, adrenals, and pituitary in pseudopregnant rats: effect of Cd on progesterone serum levels

Pseudopregnant (PSP) rats were treated with 3.5 or 7.0 mg/kg body wt of CdCl2 on Day 1 of PSP sc. In the lower dose Cd content of the ovaries (luteal and nonluteal tissues), adrenals, pituitary, and blood on Days 1, 2, 5, 8, 10, and 12, and in the higher dose that of luteal and nonluteal tissue on Days 2 and 5 of PSP were determined with atomic absorption spectrophotometry. A rapid incorporation into the corpora lutea was measured on Day 1 and Day 2 of PSP followed by a decrease of Cd content toward the end of PSP whereas the nonluteal tissue, adrenals, and pituitary accumulated Cd gradually until the fifth to 10th day, respectively. Progesterone (P) serum levels were measured with RIA in the blood collected daily from the jugular vein following administration of 3.5 to 7.0 mg/kg body wt of CdCl2 sc on Day 1 or Day 8 of PSP. The serum levels of P remained unchanged when CdCl2 was administered on Day 1 of PSP; however, 7.0 mg/kg body wt CdCl2 given on Day 8 of PSP induced a significant decrease in serum levels of P. It is supposed that the regressing luteal tissue is more sensitive to the toxic effects of Cd than the developing one.     

Tamoxifen and RU39411 synergize with mifepristone to produce preimplantation pregnancy loss by increasing embryo transport (rat)

Tamoxifen is a non-steroidal antiestrogen that possesess antagonistic as well a agonistic properties, while RU39411 is an antiestrogen that is known to possess only antagonistic properties. These steroid antagonists were administered orally to rats, with or without mifepristone, an antiprogestational agent, prior to implantation on Day 2 of pregnancy. The status of pregnancy was assessed on Day 14. Low doses of tamoxifen reduced litter size and weight and inducing embryonic absorption in some animals; a dose of 0.25 mg/Kg prevented pregnancy in all animals. RU39411 also had a dose-dependent effect on pregnancy, but a higher dose (0.5 mg/Kg) was required to achieve the same degree of pregnancy prevention. Addition of mifepristone to both antiestrogens had a synergistic effect on reducing litter size and weight.

To determine the mechanism by which antiestrogens terminate pregnancy in rats, oviducts and uteri of treated rats were examined for the presence of embryos on Day 3 and 4 of pregnancy, times when most embryos would be expected to be in the oviducts. Most of the embryos of the treated animals were found in the oviducts on Day 3 of pregnancy. By Day 4, only a few embryos were still present in oviducts. These observations suggest acceleration of embryo transport by Day 4 of pregnancy. There was no accumulation of embryos in the uterus. Since acceleration of embryo transport through the reproductive tract in rat is induced by low doses of estrogens, it is likely that the agonistic action of tamoxifen is responsible for pregnancy prevention in these experiments. The fact that RU39411 also prevents pregnancy by a similar mechanism suggests that this estrogen antagonist also has some estrogen agonist effects on the oviduct. The fact that both antiestrogens also affected embryo weight could suggest the action of the antihormones on other mechanisms controlling embryo development.     

Acute toxic effects of an isolate of moniliformin-producingFusarium oxysporum and purified moniliformin on rats

An isolate ofFusarium oxysporum (MT-6) was obtained from pasture soil in New Zealand in 1987. The isolate was grown on rice and fed to rats in a ratio of 50% and 10% of a complete diet. All rats died within 16 hr and showed mild intestinal and thymic hemorrhage. The major identifiable toxin was moniliformin found at a concentration of 9 mg/g in the rice culture. Purified crystals of moniliformin fed to rats at concentrations of 8, 5 and 3 mg/g of rat diet caused hemorrhaging in the intestines and death of 3 of 3 rats within 16 hr. Dietary concentrations of 2.5 and 2 mg/g of moniliformin killed 2 of 3 rats and concentrations of 1.5 and 1 mg/g killed 1 of 3 rats. No lesions were observed in 3 groups of 3 rats fed a diet containing 0.75, 0.5 or 0.25 mg/g of moniliformin. Intragastric intubation of moniliformin caused hemorrhage of the small intestine and death in 5 of 5 rats at each concentration of 100, 80, 60 and 40 mg/kg body weight and death of 4 of 5 rats at 20 mg/kg. No observable toxic effects were observed in groups of 5 rats each receiving 10, 5 and 2.5 mg of moniliformin/kg body weight.     

Delayed implantation induced by fadrozole hydrochloride in rats

The effect of aromatase inhibitors on the implantation process is not well known. This study examined the anti-implantation action in rats of a nonsteroidal aromatase inhibitor of high specific activity, fadrozole hydrochloride (Fad). Continuous subcutaneous infusion of Fad at 300 microg/day from Day 1 (the day of sperm detection) through Day 7 of pregnancy using a mini-osmotic pump was found to delay the initiation of implantation by 1 or 2 days with no negative effects on embryonic viability. The Fad treatment delayed preimplantation embryo development and zona shedding by embryos. The treatment also delayed the period of maximum sensitivity to a decidualizing stimulus (intraluminal infusion of sesame oil) by 2 days. The results show that continuous treatment with Fad has multiple anti-implantation effects in rats.     

Contraceptive and hormonal properties of the stem bark of Dysoxylum binectariferum in rat and docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction

BACKGROUND: This study was aimed to investigate the pregnancy interceptive activity of the stem bark of Dysoxylum binectariferum Hook. f. administered during the pre- and peri-implantation periods and immediately after implantation by oral route in adult female Sprague-Dawley rats. STUDY DESIGN: Ethanolic extract and its fractions were administered to female rats on Days 1-10, Days 1-7, Days 1-5 or Day 1 postcoitum by oral route. At autopsy on Day 12, the number and status of corpora lutea and implantations were recorded. For estrogenic activity, ovariectomized immature rats received the test extract or the vehicle once daily for 3 days and at autopsy on Day 4, uterine weight and status of vaginal opening and extent of vaginal cornification were recorded. For antiestrogenic activity, the extract was administered along with ethinyl estradiol. Docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction, to estrogen receptor (ERalpha) was conducted using AutoDock 3.0.5 on a Linux workstation. RESULTS: The ethanolic extract intercepted pregnancy in rats at a daily dose of 500 mg/kg on Days 1-7 postcoitum. On fractionation, the activity was localized in the chloroform fraction, which inhibited pregnancy in all females at the 35-mg/kg dose on Days 1-7, at the 50-mg/kg dose on Days 1-5 or at the single 300-mg/kg dose on Day 1 postcoitum. Chromatography of this fraction yielded an alkaloid, rohitukine, which prevented pregnancy at the 10-mg/kg dose administered on Days 1-7 but was partially (45%) effective at this dose when administered during the entire preimplantation period and ineffective even at 10 times this dose when administered only on Day 1 postcoitum, except that there was a significant reduction in implantation number in pregnant females. While the active chloroform soluble fraction was devoid of any estrogen agonistic or antagonistic properties, a mild uterotropic effect without induction of premature opening of vagina or cornification of vaginal epithelium was observed in rohitukine at the 10-mg/kg dose. Rohitukine, with an almost similar molecular size (mol. wt. 305) as 17beta-estradiol, fits ideally into the hydrophobic pocket of ER. While it does not appear to simultaneously interact with GLU353, ARG394 and HIS524 as estradiol to elicit frank estrogenic response, different conformations of the ligand or its metabolite(s) might acquire geometry with phenolic groups at C-3', C-5 and C-7 positions disposed in a fashion to interact with active site(s) of ER, which might be responsible for its contraceptive and/or weak uterotropic effects. The absence of a basic side chain directed toward the antiestrogen binding site (ASP351) on the receptor appears to be responsible for the lack of any estrogen antagonistic activity. CONCLUSIONS: Findings demonstrate the antifertility activity of the ethanolic extract of D. binectariferum, its chloroform soluble fraction and rohitukine. Efforts are being made to enhance the anti-implantation activity of rohitukine by structural modifications.     

Inhibition of sperm migration, fertilization and implantation in rats by precoital intrauterine administration of gossypol or nonoxynol-9

The effects of precoital intrauterine administration of Gossypol, Nonoxynol-9 or p-Aminobenzamidine on reproductive function were investigated in rats. The drugs were instilled in one uterine horn in the evening of proestrus prior to caging with a fertile male. The opposite side was similarly treated with the vehicle and served as control. Animals were killed in the morning following mating to assess the number of spermatozoa at the site of fertilization or on days 2-3 of pregnancy to determine the proportion of penetrated oocytes or on day 12 to count implanted embryos. Gossypol 0.05 to 5 mg or Nonoxynol-9 0.1 - 10 microliter reduced the number of spermatozoa reaching the ampullae and the number of penetrated oocytes in a dose-dependent fashion. At the highest dose both compounds prevented pregnancy exclusively in the treated side. p-Aminobenzamidine at a dose of 10 mg failed to affect the proportion of penetrated eggs found on days 2 or 3 of pregnancy. The results indicate that the rat bioassay is suitable to screen agents that can affect sperm function or viability since it can discriminate between drugs and doses and disclose differential effects upon sperm migration and fertilizing capacity.     

The effects of high fat feeding during one cycle of reproduction consisting of pregnancy, lactation and recovery on body composition and fat pad cellularity in the rat

The changes in adipose depot weight, cell size, cell number and body composition during pregnancy, lactation and recovery were studied in Osborne-Mendel rats fed standard or high fat diets. Rats were killed on day 21 of pregnancy, after 21 days of lactation, and after 21 or 22 days of a postlactational recovery period. Nonpregnant control groups were killed at the beginning and at the conclusion of the experimental period. The high fat-fed, mated group was always fatter than similarly treated animals fed standard diets throughout pregnancy and lactation. However, by the end of the recovery period, carcass composition of the animals fed high fat or standard diets and the nonpregnant groups were not statistically different. The weight of the parametrial, retroperitoneal and subscapular depots was higher in the high fat-fed animals at the end of the recovery period, and in the latter two pads, this increase was statistically significant. Thus, despite the extensive lipid mobilization that occurs during lactation, the high fat-fed animals appear to be predisposed to postpartum obesity.     

One cycle of reproduction consisting of pregnancy, lactation or no lactation, and recovery: effects on carcass composition in ad libitum-fed and food-restricted rats

Groups of nine ad libitum-fed and food-restricted Osborne-Mendel rats weighing between 200 and 220 g at mating were killed on day 21 of pregnancy, day 21 of lactation and day 21 of the postweaning recovery period. Restricted rats were fed 70% of the mean daily ad libitum intake. Groups of nine ad libitum-fed animals, not permitted to suckle their young, were killed on day 21 postpartum and day 21 of the recovery period. Groups of nine nonpregnant rats of comparable initial body weight were killed at appropriate times to serve as advancing age and growth controls. Changes in carcass composition were determined in each group at the end of the pregnancy, lactation and recovery periods. Carcass fat was elevated in the nonlactating group on day 21 postpartum compared to lactating animals and nonpregnant controls. At the end of the study, carcass weight was highest in the ad libitum-fed lactating group. This was due to increased carcass water and not to increased carcass fat. In fact, carcass fat was significantly reduced in the ad libitum-fed lactating group compared to nonpregnant controls. During the recovery period, the absolute increase in carcass fat was greater in the restricted group than in the ad libitum-fed group. The data indicate that 1) pregnancy followed by no lactation results in an increase in carcass fat content and 2) the postweaning recovery period is marked by a tendency to increase carcass fat even in food-restricted rats.     

Postcoital ingestion of the aqueous extract of Erythrina falcata Benth prevents pregnancy in the mouse

AIM: We examined whether the aqueous extract of Erythrina falcata, reputed to be a contraceptive in Peruvian folklore, could prevent pregnancy in the mouse. METHODS: Female mice on Day 1 of pregnancy were given aqueous extract of E. falcata or tap water (control) orally for 4 days. On Day 4 of pregnancy, animals were killed and the embryos were flushed from oviducts and uterus to examine their developmental stage, cell number, mitotic index and micronuclei frequency. Other mice were killed on Day 12 of pregnancy to determine the number of implantation sites. RESULTS: Ingestion of E. falcata diminished the percentage of embryos that progressed to blastocyst stage, reduced the cell number and mitotic index, and increased the micronuclei frequency of early embryos. The number of implantation sites was also reduced in females treated with E. falcata. CONCLUSION: The aqueous extract of E. falcata, ingested during early pregnancy, disturbs preimplantation embryo development and implantation in the mouse. These results provide the first experimental evidence of the contraceptive properties of the aqueous extract of E. falcata.     

Pregnancy interceptive activity of the roots of Calotropis gigantea Linn. in rats

OBJECTIVE: We conducted this study to evaluate the pregnancy interceptive activity of the roots of Calotropis gigantea Linn. in colony-bred adult Sprague-Dawley rats when administered during the preimplantation and/or peri-implantation periods. METHODS: The ethanolic extract of the roots of C. gigantea Linn. and its hexane, chloroform, n-butanol-soluble and n-butanol-insoluble fractions were administered to rats on Day 1, Days 1-5, Days 1-7 or Days 5-7 postcoitum. Rats from the control group received an equal volume of the vehicle (Tween 80 in glass distilled water) only. At autopsy on Day 10 postcoitum, the final body weight and number as well as status of the corpora lutea and implantations in each animal were recorded. For estrogen agonistic and antagonistic activities, 21-day-old immature rats ovariectomized 7 days earlier were treated orally with the test agent or the vehicle for 3 days. In the case of estrogen antagonistic activity, the rats also received 0.05 mg/kg of 17alpha-ethinyl estradiol for 3 days. At autopsy 24 h after the last treatment, uterine fresh weight was taken and premature opening of the vagina as well as the extent of vaginal cornification, if any, were recorded. RESULTS: The ethanolic extract of the roots of C. gigantea Linn. exhibited 100% pregnancy interceptive activity in rats when administered as a single oral dose of 100 mg/kg on Day 1 postcoitum. The extract also exhibited 100% efficacy at the dose of 12.5 mg/kg when administered in the Days 1-5 and 1-7 postcoitum schedules. When administered during the peri-cum-early postimplantation period (i.e., Days 5-7 postcoitum at 250 mg/kg), most of the implantations showed signs of resorption. On fractionation, the chloroform fraction showed 100% activity at 100 mg/kg in the single-day (Day 1 postcoitum) schedule, whereas the hexane, n-butanol-soluble and n-butanol-insoluble fractions were found to be inactive at this dose. At autopsy on Day 10 postcoitum, 7-25% loss in body weight was recorded at the minimum effective contraceptive dose (MED) in rats treated with the ethanolic extract as well as its chloroform-soluble fraction on Days 1-7, 1-5 and 1 postcoitum, in comparison with the 6-7% increase in body weight observed in vehicle control rats. There was however no mortality in any of the treatment groups. The active ethanolic extract and its chloroform fraction were devoid of any estrogen agonistic or antagonistic activity at their respective MEDs in the ovariectomized immature rat bioassay. Efforts are being made to isolate the active principles devoid of effect on body weight. CONCLUSIONS: The findings suggest the potential for developing products of this plant as contraceptives for human use and welfare. In addition, characterization of the agents responsible for body weight decrease and evaluation of their mechanism of action and safety profile, with or without contraceptive efficacy, might have added advantage for the management of obesity.     

Repeated pregnancy without lactation: effects on carcass composition and adipose tissue cellularity in rats

Four groups of Sprague-Dawley rats, 200-225 g, were mated. Two groups of rats were killed after 3 wk of nursing eight pups (PL-1) or no lactation (PNL-1). The remaining two groups went through three cycles of pregnancy/lactation (PL-3) or pregnancy/no lactation (PNL-3) and were then killed for carcass composition analysis. Two virgin groups (CON-1, CON-3) served as age controls and were killed at the appropriate time. There was a gradual reduction in food intake from cycle 1 to cycle 3 for all groups. PL-3 rats ingested significantly more food than PNL-3 rats in pregnancies of cycle 2 and cycle 3. At the end of cycle 1, there was no difference in body weight, carcass weight, fat content and fat cell cellularity in parametrial and subcutaneous fat pads between three groups of rats. However, after three cycles, the PL-3 group had significantly reduced carcass fat content because of a significant reduction in fat cell number. Repeated pregnancy followed by no lactation resulted in greater carcass fat content and fat cell number in the subcutaneous pad than observed in lactating rats, although these increases failed to reach significance when compared with virgin controls. Thus lactation may not only be beneficial to the offspring but also enhances maternal weight loss and prevents obesity in multiparous individuals.     

Importance of uterine expulsion of embryos in the interceptive mechanism of postcoital oestradiol in rats

This study compares the interceptive effectiveness of 1 microgram oestradiol given as a single s.c. injection at 0900 or 1700 hours on Day 1, 2, 3, or 4 of pregnancy in rats. Increasing the interval from ovulation to treatment accelerated the oviducal transport of a larger number of embryos, the majority of which were lost from the genital tract. However, after treatment at 1700 hours on Day 3 the majority of accelerated embryos were retained in the uterus. The number of implanted embryos on Day 14 was equal to the number of eggs remaining in the tract 24 h after treatment. As a consequence, the highest interceptive effectiveness was obtained with treatment given at 1700 hours on Day 2 and at 0900 hours on Day 3 of pregnancy. Accelerated oviducal transport and uterine expulsion of embryos begin to dissociate after Day 2 of pregnancy in the rat. This explains why the most effective treatments to accelerate oviducal transport are not always the most effective to reduce the number of implantations. These data emphasize the importance of retentive and expulsive properties of the uterus for fertility and infertility.     

Optimal levels of nitric oxide are crucial for implantation in mice

This study was performed to clarify the critical role of optimal levels of nitric oxide on fecundity in mice during the implantation period. Mature female pregnant mice were treated with either nitric oxide donor molsidomine (3, 15, 60 mg kg(-1)) or nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-name; 0.3, 1.5, 6 mg kg(-1)) every 12 h, seven times from the night of Day 2 to Day 5 of gestation. They were killed on Day 14 of gestation. Pregnancy rates in each group (n = 22) and the number of live or absorbed fetuses in each mouse was calculated. The pregnancy rates in the experimental group were reduced in a dose-dependent manner. The rate in the control group was 100%, whereas those in the 60-mg molsidomine and 6-mg L-name groups were 40.9 and 31.8%, respectively. Histological analysis of uteri on Day 5 of gestation after treatment with 60 mg molsidomine or 6 mg L-name suggested retarded decidualization of stromal cells or defective function of predecidualized cells. In conclusion, optimal levels of nitric oxide are crucial for endometrial function and embryo implantation.