Effect of vaginally administered (Ala(8,13,18))-magainin II amide on the morphology of implantation stage endometrium in the rhesus monkey (Macaca mulatta).

Intravaginal administration of an anti-microbial agent, (Ala^8,13,18)-magainin II amide, during blastocyst implantation inhibits pregnancy establishment in a dose-related manner in the rhesus monkey (Macaca mulatta). In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (Group 1; N = 5) and test agent (magainin, 0.5 mg/animal; Group 2; N = 6) on cycle day 20. Endometrial tissue samples were collected on Cycle Day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17β, progesterone, and chorionic gonadotrophin in peripheral circulation were determined, which revealed that two monkeys in Group 1 were pregnant while no animals were pregnant in Group 2. Endometrial morphology, however, revealed histologic evidence of pregnancy in three out of the six magainin-treated animals. It appears that intra-vaginal administration of magainin II amide had a marginal effect on the implantation stage endometrium and the initiation of the implantation process in the rhesus monkey.     

Anti-nidatory effect of vaginally administered fumagillin in the rhesus monkey

In the present study, fumagillin, which is an antibiotic with potent angiostatic activity secreted from Aspergillus fumigatus was administered intravaginally during peri-implantation stage in the rhesus monkey and its effects on ovarian function, blastocyst implantation and pregnancy outcome in the rhesus monkey were investigated. Female monkeys (n = 18) showing normal menstrual cycles were vaginally inserted with tampons containing fumagillin (0 mg/animal in group 1; 1 mg/animal in group 2; 2 mg/animal in group 3; 4 mg/animal in group 4) on cycle day 20 of the mated treatment cycle, and these were removed on day 26 of the treatment cycle. Pregnancy was found to occur in animals treated with 1 mg and 2 mg fumagillin. However, animals treated with 4 mg fumagillin remained non-pregnant along with decreased (p <0.001) concentration of progesterone in circulation during the luteal period compared with that in normal, non-mated, ovulatory cycle.     

Effect of vaginally administered (Ala)-magainin II amide on the morphology of implantation stage endometrium in the rhesus monkey (Macaca mulatta)

Intravaginal administration of an anti-microbial agent, (Ala^8,13,18)-magainin II amide, during blastocyst implantation inhibits pregnancy establishment in a dose-related manner in the rhesus monkey (Macaca mulatta). In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (Group 1; N = 5) and test agent (magainin, 0.5 mg/animal; Group 2; N = 6) on cycle day 20. Endometrial tissue samples were collected on Cycle Day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17β, progesterone, and chorionic gonadotrophin in peripheral circulation were determined, which revealed that two monkeys in Group 1 were pregnant while no animals were pregnant in Group 2. Endometrial morphology, however, revealed histologic evidence of pregnancy in three out of the six magainin-treated animals. It appears that intra-vaginal administration of magainin II amide had a marginal effect on the implantation stage endometrium and the initiation of the implantation process in the rhesus monkey.     

A multiparametric study of the action of mifepristone used in emergency contraception using the Rhesus monkey as a primate model

Mifepristone is a potent agent used in emergency contraception (EC). In the present study, we examined the contraceptive efficacy of mifepristone used in EC and then, using the model of mifepristone-based EC, we investigated its mechanism of action in the rhesus monkey. Sexually mature females were allowed to cohabitate with male animals from 1600 to 900 h of any one day of days 8–17 of cycle without (Group I; N = 6) and with a single dose of mifepristone (Group II, N = 31, 25 mg per animal, subcutaneous) 72 h postcoitus. Blood samples from all animals of Groups I and II were used to determine the concentrations of estradiol (E), progesterone (P) and chorionic gonadotrophin in peripheral circulation for retrospective analysis of the days of ovulation and blastocyst implantation. Four out of six animals (66.6%) in Group I became pregnant, while all 31 monkeys in Group II failed to establish pregnancy along with marginal changes in serum concentrations of E and P. In the second part of the study, animals were subjected to the same experimental protocol followed by collection of endometrial tissue samples on cycle day 22 from animals of both Group I (n = 6) and Group II (n = 24). Endometrial samples were subjected to morphological analysis including mitotic index, immunohistochemistry for vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), transforming growth factor β1, estradiol receptor (ER), progesterone receptor (PR), proliferating cell nuclear antigen, placental protein 14 (PP 14) and detection of apoptosis by terminal nick end labeling method followed by histometric analysis. The results were retrospectively analyzed between the two groups on the basis of the day of treatment after ovulation: early luteal phase (days 0–3 postovulation) and mid-luteal phase (days 4–7 after ovulation). Mifepristone used in EC in the present study resulted in general loss of functional integrity of epithelial compartment characterized by loss of secretory maturation, increased apoptosis and higher degree of degeneration along with decreased expression of VEGF, LIF, PP14 and ER, while PR level increased as compared to control samples. The vascular compartment appeared to be compromised along with affected morphological features and decreased expression of VEGF, LIF, ER and PR following the administration of mifepristone. It appears that mifepristone used in EC alters the physiological homeostasis in epithelial and vascular compartments of implantation stage endometrium rendering it hostile to blastocyst implantation. Furthermore, the degree to which the endometrial function is affected largely depends on the day of mifepristone treatment in a parameter-specific manner resulting in a higher degree of degenerative changes in samples obtained from animals who received mifepristone during mid-luteal phase of cycles.     

Embryo transfer in the dromedary camel (Camelus dromedarius) using non-ovulated and ovulated, asynchronous progesterone-treated recipients

The aim of the present study was to investigate the use of exogenous progesterone and equine chorionic gonadotrophin (eCG) in non-ovulated and ovulated, asynchronous dromedary camel recipients being prepared for an embryo transfer programme. The uteri of 12 mated donor camels were flushed non-surgically 7 days after ovulation and 42 embryos were recovered. In Experiment 1, 16 embryos were transferred non-surgically to recipients on Day 3 or 4 after ovulation (ov+3 and ov+4, respectively). Each recipient received a daily dose of 75 mg, i.m., progesterone-in-oil from 2 days before embryo transfer until 6 days after ovulation. Thereafter, the progesterone dose was reduced to 50 mg on Day 7 and finally to 25 mg day(-1) on Days 8 and 9. Nine of 16 recipients (56%; ov+3, n=4; ov+4, n=5) became pregnant compared with none of eight non-progesterone treated controls, into which embryos were transferred on Day 4 after ovulation. In Experiment 2, 18 non-ovulated recipients received 75 mg, i.m., progesterone-in-oil daily from 3 days before until 12 days after non-surgical transfer of a Day 7 blastocyst, at which time pregnancy was diagnosed by ultrasonography. All pregnant recipients continued to receive 75 mg progesterone-in-oil daily for a further 6 days, when each camel received 2000 IU, i.m., eCG. Progesterone treatment was then reduced to 50 mg day(-1) and, when a follicle(s) ≥1.3 cm in diameter were present in the ovaries, each animal received 20 μg buserelin to induce ovulation. Once the corpora lutea had developed, progesterone treatment was reduced to 25 mg day(-1) for a final 3 days. Fourteen of 18 recipients (78%) became pregnant and seven of these (50%) remained pregnant after eCG treatment. Of the seven pregnancies that were lost, two were lost before eCG treatment, two did not respond to eCG treatment and three responded to eCG treatment and ovulated, but lost their pregnancies 6-8 days after the last progesterone injection.     

Target-oriented anti-implantation approaches for pregnancy interception: experiences in the rhesus monkey model

Blastocyst implantation is a critical process in the establishment of pregnancy in eutherian mammals and requires a harmonious symbiosis between the developing conceptus and the differentiating maternal uterus. A better understanding of this symbiotic relationship will provide novel approaches and interventions for realizing anti-implantation strategies for effective fertility regulation and reproductive health care management. We have been using the rhesus monkey (Macaca mulatta) as a nonhuman primate model to this end. In the present study, the process of progesterone-mediated regulation of endometrial receptivity for blastocyst implantation has been targeted by the use of mifepristone as an emergency contraceptive agent. Furthermore, based on cell-specific, temporal and spatial distribution of vasotropic cytokines and mediators in the "receptive" and periimplantation periods, the pregnancy interceptive potentials of (a) monoclonal antibody (MAb) to leukemia inhibitory factor (LIF); (b) inhibitors of nitric oxide synthase [e.g., N6-nitro-l-arginine (l-NAME) and aminoguanidine]; and (c) MAb to vascular endothelial growth factor (VEGF) were examined. LIF is a progesterone-responsive pleiotropic cytokine that functions as a proinflammatory cytokine, together with interleukins 1 and 6, during the process of implantation-placentation in primates, and its immunoneutralization with MAb resulted in inhibition (p<.04) of pregnancy establishment in the rhesus monkey. However, timed administration of l-NAME or aminoguanidine failed to inhibit blastocyst implantation in a significant manner. Also, no synergistic antinidatory action of antiprogestin combined with l-NAME was detected in the rhesus monkey. The application of MAb to VEGF during the periimplantation period, on the other hand, led to significant (p<.04) prevention of pregnancy without influencing steroid hormone levels in the circulation. Our data lend support to the hypothesis that VEGF is essential for pregnancy establishment and that trophoblast-derived VEGF, acting via its specific receptors Flt-1 and KDR, is necessary for blastocyst implantation. The use of cDNA-based expression arrays followed by differential display analysis has provided preliminary understanding of the nature of gene cluster networks operative in the receptive endometrium of potential conception cycles in the rhesus monkey. This knowledge may, in the future, lead to further innovative anti-implantation strategies for targeted pregnancy interception.     

Effect of vaginally administered fumagillin on the morphology of implantation stage endometrium in the rhesus monkey

Intravaginal administration of an anti-angiogenic agent, fumagillin, during blastocyst implantation, inhibits pregnancy establishment in a dose-related manner in the rhesus monkey. In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial tissue samples were collected on cycle day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From serum profiles of hormones, two monkeys in group 1, and one animal in group 2 appeared pregnant. Endometrial morphology revealed histologic evidence of pregnancy in three of six fumagillin-treated animals, while other three fumagillin-treated animals showed degenerative changes in glands and venules along with marked extravasation. It is possible that the function of corpus luteum was affected by fumagillin treatment resulting in inadequate progesterone production (p <0.05), and consequent inadequate endometrial secretory preparation and receptivity, as revealed from decline in apical movement of vacuoles (p <0.05) and increase (p <0.05) in extravasation of red cells and leukocytes.     

Anti-nidatory effect of vaginally administered (Ala8,13, 18)-magainin II amide in the rhesus monkey

The hypothesis that timed application of a potent anti-microbial, anti-tumor agent like magainin peptides can inhibit blastocyst implantation was examined in the present study using the rhesus monkey as the primate model. Incidence of pregnancy, vaginal bleeding patterns, serum levels of progesterone, estrogen and monkey chorionic gonadotropin were examined following vaginal administration of (Ala8,13,18)-magainin II amide, a synthetic analogue of magainin 2, via tampon during days 20 to 26 of mated cycles. Implantation occurred in two out of three animals following administration of 0.25 mg magainin, while administration of 0.5 mg (Ala8,13,18)-magainin II amide resulted in inhibition of implantation in all females with no change in lengths of treatment cycles, and subsequent cycles. It appears from the present study that, besides being a local microbicidal agent, intravaginal administration of (Ala(8,13,18))-magainin II amide is a potential anti-implantation strategy for intercepting pregnancy.     

Irisin对肥胖大鼠子宫内膜功能的影响

目的：观察鸢尾素（Irisin）对肥胖大鼠子宫内膜功能的影响。方法：选用成年雌性SD大鼠,采用高脂饲料建立肥胖模型;正常组给予正常饮食。将造模成功大鼠随机分为肥胖模型组（16只）和Irisin组（16只）,另设对照组（16只）。其中,Irisin组腹腔注射重组Irisin[100 ng/（g·d）×14 d],肥胖模型组和对照组腹腔注射生理盐水,并于注射前后记录大鼠体质量。后于动情期内合笼,于大鼠妊娠D5、D10天每组各处死8只大鼠,记录妊娠率及平均胚泡着床数,观察子宫内膜组织形态;检测大鼠子宫内膜白血病抑制因子（LIF）、整合素αvβ3蛋白及mRNA的表达。结果：Irisin组经腹腔注射Irisin 14 d后,大鼠体质量低于肥胖模型组,差异有统计学意义（P=0.035）。肥胖模型组平均胚泡着床数比对照组和Irisin组低,差异有统计学意义（均P＜0.05）。对照组大鼠子宫内膜宫腔饱满,胚胎发育好;肥胖模型组大鼠子宫腔间隙较大,胚胎发育不良;Irisin组大鼠子宫腔接近闭合,胚胎发育良好。肥胖模型组子宫内膜LIF、αvβ3的蛋白表达量和mRNA含量比对照组和Irisin组低,差异有统计学意义（均P＜0.05）。结论：Irisin可通过增加子宫内膜LIF、αvβ3的表达,从而改善肥胖大鼠子宫内膜容受性。     

Effect of chemical sympathectomy and adrenergic agonists on the fertility of mice.

These experiments were designed to determine whether the adrenergic nerves present in the mouse oviduct are required for normal fertility and whether alpha and beta adrenergic agonists could modify fertility. Female hybrid mice were placed with fertile males. The presence of a vaginal plug was considered Day 1 of pregnancy. From Days 1-5 the mice were given 1 of the following drugs injected intraperitoneally 2 times a day: oxymetazoline hydrochloride, methoxamine hydrochloride, salbutamol sulphate, or isoproterenol hydrochloride. Controls received only the diluent. All were sacrificed on Day 12 of pregnancy and the number of fetuses recorded. Another group of mice received 6-hydroxydopamine hydrobromide in .1 ml of diluent intraperitoneally daily in doses from 8 mg/kg on Day 1, 12 mg/kg on Day 2, 15 mg/kg on Day 3, and 40 or 60 mg/kg on Day 4. Mice were mated on Day 5 and sacrificed on Day 19 when fetuses were counted. To determine completeness of denervation other animals so treated were sacrificed on Day 7 and the ovaries and oviducts studied. An 80% reduction in uptake of tritiated metaraminol in oviducts and ovaries was shown while fluorescence microscopy indicated that the oviducts and ovaries were essentially completely adrenergically denervated. The 6-hydroxydopamine pretreatment did not affect the fertility of the mice. Denervation of peripheral tissue was only partial. Of the drugs tested (oxymetazoline, methoxamine, salbutamol, and isoproterenol) only oxymetazoline at the highest dose levels had any effect on fertility. It was concluded that the presence of a functional adrenergic innervation is not necessary for normal ovulation or ovum transport and that only the long-acting potent alpha agonist oxymetazoline affected mouse fertility.     

Dose-related actions of GnRH II analog in the cycling rhesus monkey

INTRODUCTION: Gonadotropin-releasing hormone (GnRH) II expression, specific high-affinity receptors for GnRH II and its potent bioactivity in human and baboon tissues led us to hypothesize that GnRH II is a bioactive peptide in primates. We recently demonstrated the contraceptive activity of GnRH II analog in rhesus monkeys. In the present experiment, we extended those studies to the dose-related action of this analog on parameters of luteal function and conception. METHODS: GnRH II analog (0-32 microg/day) or saline was administered via osmotic minipumps for 6 days (Days 1-6 postovulation) to regularly cycling rhesus monkeys mated with fertile males around the time of ovulation. Cycle dynamics was monitored through circulating luteinizing hormone, progesterone and estradiol. Pregnancy was determined by circulating chorionic gonadotropin concentrations. RESULTS: Progesterone production (Days 3-11) was significantly less (p<.05) for animals treated with 2, 4 or 8 microg/mL GnRH II analog than for controls, yet with higher doses of GnRH II analog (i.e., 16 or 32 microg/day), luteal progesterone was not different from that of saline-treated controls. The length of the luteal phase in all treated groups was similar to that of controls. In 18 animals mated at the time of ovulation and then treated with GnRH II analog (2-32 microg/day), no pregnancies resulted. In saline-treated controls, five of eight animals (62.5%) became pregnant. Thus, the contraceptive activity of this GnRH II analog did not correlate with luteal progesterone inhibition. CONCLUSIONS: These data demonstrate a dose-related action of GnRH II analog on luteal progesterone and establish the contraceptive activity of 2-32 microg/day GnRH II analog administered postovulation.     

Investigation on some biochemical parameters and effect of hormonal treatment in anoestrous dairy cows with cystic ovarian follicle

ObjectiveTo investigate some blood biochemical parameters in anoestrous dairy cows with cystic ovarian follicles (COF) during the first two months post partum and the effect of hCG-PGF2_α -GnRH treatment on their reproductive response.MethodsThe investigation was performed on 20 lactating Holstein cows, divided into two groups: control group (n=8) and treated group (n=12). All animals had cystic ovarian follicles, detected during the two consecutive transrectal ultrasound examinations at 7-day interval. Blood samples from each animal were collected on the day of second ultrasonography (Day 0) and subjected to a hormonal and biochemical analysis. Treated cows were subjected to another ultrasound examination on day of prostaglandin injection and the presence of corpus luteum was recorded. The control animals were not treated, while the treated group received 1 500 IU hCG on day 0, PGF2_α 500 mg on day 7 and 100 μg GnRH 48 hours latter. Eighteen hours after GnRH administration animals bearing corpus luteum on Day 7 were artificiallly inseminated. The last ultrasound examination was made forty days after start of the threapy. On the base of the obtained results, cumulative oestrous activity, cumulative ovulation rate, pregnancy rate and COF persistence were determined.ResultsThe blood analysis in the both groups on Day 0 showed significantly (P<0.05) lower mean concentration of progesterone, glucose and inorganic phosphate compared to the reference range values for cyclic dairy cows. Cumulative oestrous activity (91.7%) and cumulative ovulation rate (75.0%) were considerably higher (P<0.05) in treated group than control group, whereas the cystic follicle persistence (25.0%) was lower (P<0.05) in the treated group than control group.ConclusionsThe present study confirmed the thesis for low blood levels of glucose and inorganic phosphate in cows presenting cystic ovarian follicles. It also indicated significant improvement of cumulative oestrous activity and ovulation rate in animals subjected to hCG-PGF2_α -GnRH administration than non-treated animals. The used hormonal protocol could decrease cystic ovarian follicle persistence in dairy cows.     

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.     

Histomorphometry and expression of Cdc47 and caspase-3 in hyperthyroid rat uteri and placentas during gestation and postpartum associated with fetal development

In two different experiments, the effects of hyperthyroidism on the histomorphometry and expression of Cdc47 and caspase-3 were evaluated in the uteri and placentas during gestation and postpartum. Fetal development was also evaluated during gestation. In the first experiment, 36 adult female Wistar rats were divided into two groups of 18 animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed at 7, 14 and 19 days of gestation. Uteri and placentas were weighed and subjected to histomorphometric and immunohistochemical evaluation to determine the expression of Cdc47 and caspase-3. Ovaries were also evaluated for weight and subjected to morphometric analysis. Fetuses were quantified and weighed individually. In the second experiment, 12 adult female Wistar rats were divided into two groups of six animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed 2 days postpartum. Uteri were evaluated in the same way as for the first experiment. Hyperthyroidism increased ovulation and conception rates without disturbing the size and viability of the fetuses. In the pregnant uteri, hyperthyroidism did not change the thickness of the layers or the expression of Cdc47 and caspase-3. However, in the placentas, hyperthyroidism increased the medium diameter of trophoblast cells, as well as the thickness and the expression of Cdc47 of spongiotrophoblast cells, at 14 days of gestation. During uterine involution, hyperthyroidism significantly increased the expression of Cdc47 and reduced the expression of caspase-3 in the uterine layers. In conclusion, hyperthyroidism increased the conception rate because of an ovulation gain, induced significant placental changes during pregnancy and, in the uterus, increased Cdc47 expression and decreased caspase-3 expression after parturition.     

Embryo transfer in the dromedary camel (Camelus dromedarius) using asynchronous, meclofenamic acid-treated recipients

A total of 40 (Day 7) embryos were recovered from the uteri of 10 superovulated camels. Recipient camels (n = 30) were prepared by injection with 20 (1/4)g of the gonadotrophin-releasing hormone analogue buserelin (i.v.) to induce ovulation and then treatment with 1 g meclofenamic acid (a prostaglandin synthetase inhibitor), orally, once on Day 7 and twice daily on Days 8 and 9 after ovulation and thereafter at a dose of 1 g day(-1) until 8 days after embryo transfer. Embryos were transferred into recipients on Day 8 (n = 10), Day 10 (n = 10) or Day 12 (n = 10) after ovulation and another 10 embryos were transferred into untreated recipients on Day 8 after ovulation as controls. In addition, serum samples from all recipient camels were recovered daily throughout the period of meclofenamic acid administration and for a further 7 days after treatment had ceased and were assayed for progesterone concentrations. Results showed that whereas only one of 10 of the control group of recipients (10%) was diagnosed pregnant, a total of eight of 10 Day 8 (80%), six of 10 Day 10 (60%) and seven of 10 Day 12 (70%) recipients were diagnosed pregnant by ultrasonography 12 days after the embryo had been transferred. Subsequently, however, four pregnancies were lost when the conceptus was aged between 22 and 60 days, but this is not considered above the early fetal mortality rate expected in camels after natural mating or after transferring camel embryos to untreated recipients. Serum progesterone concentrations remained elevated, above 2 ng mL(-1), throughout the period of meclofenamic acid administration in all recipient camels; thereafter, concentrations remained above 2 ng mL(-1) in pregnant animals, whereas in non-pregnant camels concentrations had declined to baseline values (<1 ng mL(-1)) within 3 days of the end of the treatment period. In conclusion, treatment of recipient camels with meclofenamic acid reduced the need for tightly timed synchrony between donor and recipient because pregnancies were established in recipients that had ovulated as much as 5 days ahead of the donor.     

Effect of systemic progesterone concentration on the expression of progesterone-responsive genes in the bovine endometrium during the early luteal phase

Increasing evidence indicates an association between the concentration of systemic progesterone during the early luteal phase of the oestrous cycle and embryo survival rate in cattle. We examined the relationship between the concentration of systemic progesterone on Days 4 to 8 post-ovulation and expression of progesterone receptor (PGR), oestrogen receptor +/- (ESR1) and retinol-binding protein (RBP) mRNA in the bovine endometrium. Heifers were blood sampled from the day of ovulation (Day 0) to Day 8 post-ovulation. On Day 4, animals were divided into low progesterone control (LC) and high progesterone control (HC) groups based on their plasma progesterone concentrations. Half of each group was supplemented with exogenous progesterone resulting in two further groups, low progesterone supplemented (LS) and high progesterone supplemented (HS). Endometrial tissues were recovered from all groups on Day 6 or Day 8 and gene expression was analysed following Northern blotting. Increasing progesterone concentrations were associated with decreased PGR and ESR1 expression. Duration-dependent effects of progesterone supplementation on ESR1 were evident and there was an effect of systemic progesterone concentrations between Day 0 and Day 4 on the expression of RBP at Days 6 and 8. Such progesterone-responsive changes in uterine gene expression are likely to affect embryo development.     

Win 32,729, a new, potent interceptive agent in rats and rhesus monkeys

Win 32,729 [(2 alpha, 4 alpha, 5 alpha, 17 beta)-4,5-epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane-2-carbonitrile] is an orally active interceptive agent in rats and rhesus monkeys (M mulatta). A single oral dose of 48 mg/kg terminated gestation when given on Day 10 of pregnancy. When given orally for up to 5 days to pregnant monkeys, it terminated pregnancy in 26 of 34 animals at a dose of 50 mg/monkey (ca 7 mg/kg), in 18 of 24 at a dose of 100 mg/monkey (ca 14 mg/kg) and in all 6 at 250 mg/monkey (ca 35 mg/kg). It did not inhibit ACTH-stimulated glucocorticoid production at 50 mg/monkey but did at a dose of 250 mg/monkey. This preferential gonadal inhibition was not evident in rodents. While in most cases five oral medications of 50-100 mg were required to terminate gestation in 50-day pregnant monkeys, a single subcutaneous medication with 250 mg was also effective, terminating pregnancy in 7 of 7 monkeys.     

Effects of conceptus and conceptus secretory products on uterine development in the pig

Pregnant gilts (n = 6) were subjected to surgery on Day 3 of pregnancy and uterine horns, within gilts, were assigned to either (1) ligation 15 cm below the uterotubal junction (REST) or (2) ligation proximal to the uterine body (NONREST). On Day 15 of pregnancy gilts were hysterectomized and length and weight of both uterine horns were recorded. NONREST uterine horns were longer (P less than .05) than those of REST, but weights were similar. Conceptuses from the REST uterine horns were retarded in development. Morphometric analysis of surface (SE) and glandular (GE) epithelial cells detected no effect of treatment on height, width, area, nuclear area or percentage of nucleus. Porcine conceptus secretory proteins (pCSP) were obtained from medium in which pig conceptuses, collected on Day 15 of pregnancy, were cultured for 30 h. Culture medium was pooled, dialysed and concentrated by Amicon ultrafiltration for intrauterine infusion. Serum proteins (SP) were obtained from blood collected from a Day 15 pregnant gilt and diluted for intrauterine infusion. Catheters were placed into both uterine horns or cyclic gilts (n = 8) on Day 10 of the oestrous cycle and uterine horns were ligated proximal to the uterine body. Gilts received either oestradiol valerate (E2) (5 mg) or corn oil (CO) on Days 11 and 12. On Days 12-14 each gilt received twice daily infusions of Day 15 pCSP in one uterine horn and SP in the other uterine horn.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine effects of chlorinated hydrocarbons in rhesus monkeys.

After the rhesus monkey was demonstrated to be a suitable model for man in both metabolic and endocrinological studies, effects of hexachlorobenzene (HCB) and polychlorinated biphenyls (PCB) on the pattern of sexual hormones in cycling female rhesus monkeys were investigated. After confirmed ovulation, four adult female rhesus monkeys were treated during the following cycle with 4 mg/kg/day of HCB, and four other monkeys were treated with the same dose of Clophen A 30. Ovulation was blocked in three PCB-treated and one HCB-treated monkeys. Whereas the levels of luteinizing hormone and follicle-stimulating hormone did not seem to be changed directly by the treatment, low estrogen levels were found during the anovulatory cycles. Studies with PCB- and HCB-treated superovulated rats indicated interaction of the chemicals with ovarian steroidogenesis. Altered hepatic steroid metabolism may also cause low estrogen levels in treated animals.