Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

Analysis of the endometrial transcriptome at the time of implantation in women receiving a single post-ovulatory dose of levonorgestrel or mifepristone

Abstract Background: Levonorgestrel (LNG) is a progesterone receptor agonist used in both regular and emergency hormonal contraception; however, its effects on the endometrium as a contraceptive remain widely unknown and under public debate. Objective: To analyze the effects of LNG or mifepristone (MFP), a progesterone receptor antagonist and also known as RU-486, administered at the time of follicle rupture (FR) on endometrial transcriptome during the receptive period of the menstrual cycle. Methods: Ten volunteers ovulatory women were studied during two menstrual cycles, a control cycle and a consecutively treated cycle; in this last case, women were randomly allocated to two groups of 5 women each, receiving one dose of LNG (1.5 mg) or MFP (50 mg) the day of the FR by ultrasound. Endometrial biopsies were taken 6 days after drug administration and prepared for microarray analysis. Results: Genomic functional analysis in the LNG-treated group showed as activated the bio-functions embryo implantation and decidualization, while these bio-functions in the T-MFP group were predicted as inhibited. Conclusions: The administration of LNG as a hormonal emergency contraceptive resulted in an endometrial gene expression profile associated with receptivity. These results agree on the concept that LNG does not affect endometrial receptivity and/or embryo implantation when used as an emergency contraceptive.

Effects of melatonin and prolactin in reproduction: review of literature / Efeitos da melatonina e da prolactina na reprodução: revisão de literatura.

Summary The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

Resumo A glândula pineal é responsável pela produção do hormônio melatonina (MEL), sendo aceita como a glândula reguladora da reprodução em mamíferos. A prolactina (PRL) também exibe atividade reprodutiva em animais, em resposta ao fotoperíodo. Sabe-se que as concentrações de PRL são elevadas durante o verão e baixam durante o inverno, ocorrendo o oposto com os níveis do hormônio melatonina nessas estações. Nos mamíferos placentários, tanto a melatonina quanto a prolactina influenciam a implantação, que é considerada o ponto crítico da gravidez, pois o sucesso da gestação requer o desenvolvimento de uma interação sincronizada entre o endométrio e o blastocisto para o desenvolvimento da placenta. Sabe- -se ainda que os níveis de PRL durante a gestação são essenciais para a manutenção da gravidez, pois esse hormônio induz o corpo lúteo a produzir progesterona, além de estimular a implantação do blastocisto, mantendo a prenhez e o desenvolvimento placentário. Em contrapartida, tem-se demonstrado também que os níveis de melatonina no plasma aumentam durante a gestação, atingindo valores elevados no fim desse período, sugerindo que esse hormônio desempenhe um importante papel na manutenção da gestação. Dessa forma, fica claro que o tratamento com prolactina ou melatonina interfere nos processos responsáveis pelo desenvolvimento e pela manutenção da gestação.

Antifertility effect of Melia azedarach Linn. (dharek) seed extract in female albino rats.

In the present study, the effect of oral administration of Melia azedarach Linn. (dharek) seed extract on fertility index, uterine weight and various histological and biochemical parameters of uterus were studied in the adult cyclic Wistar rats. Average number of embryos and implantation losses in the pregnant animals treated with dharek seed extract was also studied. The extract was prepared using a flash evaporator at 35 degrees C and dissolved in olive oil to prepare doses on per kg body weight basis. The results indicated a reduction in fertility index and average number of embryos in mated rats treated with the dharek extract. Pre-implantation, post-implantation and total prenatal mortalities were increased in rats treated with dharek seed extract during early (D1-D7) and late (D7-D18) stages of gestation period at doses of 5, 10 and 20 mg kg(-1) body wt day(-1). Histological studies showed a significant reduction in myometrial thickness, uterine gland diameter, luminal diameter of uterine glands and luminal epithelial cell height in rats treated with dharek seed extract at 1mg kg(-1) body wt day(-1) for 18 days. Pits and folds in luminal epithelial, mitotic activity in luminal and glandular epithelial cells of uterus were observed to be absent. Biochemically, a significant increase in protein and glycogen contents was observed. Thus, in conclusion, the application of this plant extract in rodent control programme may help to elevate the socioeconomic status of the society.

Progesterone therapy administered 24 hours before embryo transfer in ICSI cycle improves embryo implantation and pregnancy in women with Luteal Phase Defect

Ovulation induction by human menopausal gonadotrophin [HMG] results in temporal luteal phase defect. Luteal support therapies are required to support embryo implantation in stimulated cycle especially in luteal phase defect infertile women. The objective of the present study was to investigate the clinical significance of progesterone, aspirin and HCG on human embryo implantation in women with luteal phase defect following ICSI and embryo transfer [ET]. The female patients were divided into six groups depending on the type of the luteal support protocols [LSP]. Group 1 [No= 54], received 10 mg oral progesterone [P], group 2 [No= 35] received P plus HCG, group 3 [No= 59] received P plus HCG plus oral aspirin, group 4 [No= 47] received vaginal P administered 24 hours before embryo transfer plus oral aspirin, group 5 [No= 40] received vaginal P administered 12 hours after embryo transfer plus oral aspirin and group 6 [No= 46] received intramuscular P plus oral aspirin. The LSP were continued for at least 12 weeks, when the B-HCG test was positive, [tested two weeks after embryo transfer]. Statistical analysis of the clinical data showed no significant differences between the LSP in regard to patient's age, body mass index [B/M2], basal FSH/LH ratio and estradiol concentration at the day of HCG injection. The ICSI rate, percentages of embryos developed in vitro, and the numbers of the transferable quality embryos were similar in all groups [P>0.05]. The pregnancy rate was significantly higher [P < 0.05], in group 4 compared to other groups [38.66% versus 24.51%[G I], 22.53% [G 2], 28.66% [G 3], 25% [G 5], 21.60% [G 6]. The percentages of viable fetal sac development per patient were 31.49 [17/54] in G 1, 42.86 [15/35] in G 2, 49.16 [29/59] in G 3, 59.58 [28/47] in G 4, 32.50 [13/40] in G 5, and 34.79 [16/46] in G 6. The percent of viable gestation sac was significantly higher in group 4 compared to other groups [P < 0.05]. The administration of 400 mg /day vaginal progesterone 24 hours before ET and 100 mg/day aspirin five days after ET results in significant improvements in pregnancy and embryo implantation rates and development of viable fetuses in luteal phase defect infertile women undergoing ICSI-ET

Effect of low-dose aspirin therapy on implantation rate in women undergoing in-vitro fertilization cycles

To determine the effect of low-dose aspirin on ovarian response, implantation and pregnancy rates in patients undergoing in-vitro fertilization [IVF] cycles. We performed a randomized analysis of 145 infertile women with a mean +/- SD age of 29.6 +/- 4.47 years who underwent cyles of IVF. Patients received 100 mg of aspirin [n=72] or placebo [n=73] daily. This study was conducted in Royan Institute, Tehran, Iran from April 2002 to January 2004. Aspirin was started on the 21st of their preceding menstrual cycle and it was continued until menstruation or a negative pregnancy test. Pregnant women received the medication until 12 weeks of pregnancy. The main outcome measures were number of follicles >/= 15mm, number of oocytes retrieved, serum E2 levels, cancellation rate, Ovarian Hyperstimulation Syndrome [OHSS] occurrence, number of embryos transferred, and implantation and pregnancy rates. There were statistically significant differences between the treatment group and the control group in the number of follicles [7.4 +/- 4.1 versus 9.0 +/- 4.8] and OHSS occurrence [5.6% versus 23.3%] but not in the other measures. The addition of aspirin low dose [100 mg/daily] to the standard long protocol for oocyte retrieval did not improve implantation and pregnancy rates in unselected patients undergoing IVF cycles

Effects of Meloxicam on Implantation and Parturition of Rat

Meloxicam, a selective cyclooxygenase-2 preferential inhibitor, was studied for its anti-implantation and parturition effects on pregnant rats. Regarding the effect of meloxicam on implantation, rats were dosed orally by 7.5 and 10 mg/kg/day from day 1 through 3 or from day 3 through 5 of gestation, respectively. While for the parturition effect, rats were dosed orally by the above doses from day 20 through 22 of gestation. The results of implantation experiments showed that the number of implantation sites was significantly decreased in all treated groups in a dose- and time-dependent manner. Whereas the number of resorption sites were significantly increased in all meloxicam treated groups. On the other hand, the results of parturition experiments indicated that meloxicam significantly prolonged the duration time of delivery in a dose-dependent manner. Further, significantly less viable fetuses and pups were delivered per female treated with meloxicam. In conclusion, the results indicate that meloxicam exhibited potential effect on implantation and parturition processes of pregnant rats

Study of anti-fertility effect of lemon seeds (Citrus limonum) in female albino mice.

Among the citrus species, Citrus-limonum is native of North West region of India. The petroleum ether, alcoholic and aqueous extracts of Citrus-limonum (lemon) seeds were investigated for anti-fertility effect in female albino mice. The extracts were administered orally for 7 days after insemination (i.e. post-ovulatory test). The control group received 4% gum acacia. The animals were examined for implantation sites on 10th day of pregnancy and the number of pups delivered at term for each group was recorded. The alcoholic extract showed significant anti-fertility effect as compared to petroleum ether and aqueous extracts. The alcoholic extract was subjected for fractionation and the fractions were again tested for their anti-fertility effect. The fraction of ethyl-acetate (12-25 fractions) showed most encouraging anti-fertility activity. In second part of the study, the alcoholic extract and its ethyl-acetate fraction (12-25 fractions) were subjected to evaluation of their mechanism of action and it was found that their principal mode of action is as an anti-zygotic agent. Withdrawal of the test drug, resulted in complete restoration of fertility. Thus the ethyl-acetate fraction (12-25 fractions) of alcoholic extract of lemon seeds exerted reversible anti-fertility effect in female mice by virtue of its anti-zygotic action.

possible role of nitric oxide [NO] in ovarian steroidogenesis, ovulation and implantation in the rat

Evaluation of the effects of nitric oxide [NO] on the ovarian functions including ovulation and steriodogensis [serum 17-beta estradiol and progesterone concentrations] and to verify if nitric oxide is an essential mediator in embryonic implantation in the rat. Fifty female albino rats devided into 2 major groups, group [1] and group [2]: group [I] consisted of thirty prepubertal female rats injected with 5IU pregnant mare's serum gonadotropin [PMSG] intraperitoneal [I.P.], followed after 48h by I.P. injection of 5IU human chorionic gonadotropin [hCG], this group was further subdivided into 3 subgroups each of ten rats: Group IA saline treated group served as control, group IB [L-NAME treated group], group IC [L-NAME + sodium nitroprusside [SNP] treated group] both groups injected I.P. in a single dose. Twenty four hour later, blood samples were collected to measure levels of serum total nitrite, progesterone and 17 beta estradiol concentration then both ovaries removed and weighted, the ratio of ovarian weight / total body weight was obtained, number of ovarian and graafian follicles rupture sites were assessed as well. Group II consists of 20 mature pregnant rats divided into 2 sub groups [IIA, IIB] on the third day of pregnancy both uterine horns were exposed and [L-NAME] was injected [Group IIA] and [L-NAME+SNP] in the second [group IIB] into one of the uterine horns, animals allowed to recover on the eighth day of pregnancy, gravid uteri were dissected out and inspected for implantation sites. In group I [hCG] administration after [PMSG] in prepubertal rats produce superovulation. Injection of [L-NAME] [I.P.] after [PMSG] and [hCG] administration, showed a significant reduction in serum total nitrite concentration, serum progesterone and estradiol were elevated, also there was a decrease in ovarian and graafian follicles rupture sites. Ovarian weight was decreased although body weight was not changed indicating the specific effect of NO on ovarian tissue. NO generator [SNP], reverse the inhibitory action of L-NAME on the serum total nitrite levels, ovulatory process and the stimulatory action on steriodogensis as no significant difference was detected in ovarian and graafian follicles rupture sites, ovarian weight, serum progesterone and estradiol concentration compared to control group. In group II: administration of L-NAME on the third day of pregnancy significantly reduced the implantation sites. Coadministration of [SNP] with [L-NAME] showed that SNP reversed the anti-implantation effect of L-NAME. [1] Nitric oxide plays an important role in the regulation of steriodogensis and ovulation. This is evident as after injection of [NOS] inhibitor [L-NAME] there was reduction in the number of both ovarian and graafian follicles rupture sites. Also decrease in ovarian weight and ovarian/body weight ratio was observed. Level of serum 17 beta estradiol and progesterone were elevated, the reversal of these effects by coadministration of a [NO] donor SNP plus L-NAME was present. [2] Nitric oxide is involved in embryonic implantation as inhibition of NOS by L-NAME led to and implantation failure where as co-treatment with [SNP] abolished this inhibitory effect

Anti-angiogenic activity of BIM (bio-immunomodulator).

Angiogenesis and immune suppression are the two important factors responsible for embryo implantation and development of tumor. Therefore, disruption of angiogenesis and upliftment of immune function is essential for control of tumor growth as well as to regulate the activity of post coital contraceptives. BIM is an immunomodulatory cytokine obtained from rodent bone marrow that showed anti-implantation and anti-tumor activities. It also improved T/B cell and monocyte macrophage functions. In this communication the anti-angiogenic property of BIM is demonstrated in pregnant rat model. BIM induced disintegration of uterine myometrium and blood vessels. No implantation was observed compared to control. It is proposed that depending upon the physiological condition of the host BIM could modulate host immune function and exert its anti-angiogenic effect.

Effect of vaginally administered fumagillin on immunohistochemical distribution of leukemia inhibitory factor, interleukin 6, transforming growth factor beta and vascular endothelial growth factor in implantation stage endometrium of 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 histological examination and immunohistochemical localization for LIF, IL-6, TGF-beta and VEGF. Concentrations of estradiol-17 beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From the serum profiles of the hormones, 2 monkeys in group 1, and 1 monkey in group 2 appeared pregnant. However, endometrial morphology revealed histological evidence of pregnancy in 3 out of 6 fumagillin-treated animals. Histometric analysis of immunohistochemical staining in epithelial, stromal and vascular compartments revealed that per cent areas occupied by immunoprecipitate for the cytokines studies did not change in epithelial and stromal compartments, except that for TGF-beta which was higher (P < 0.05) in epithelial compartment in group 2. No change was observed in immunoprecipitation areas for IL-6 in epithelial, stromal and vascular compartments. On the other hand, changes (P < 0.05) for LIF, TGF-beta and VEGF were evident in the vascular compartment. It is possible that disparate responses observed in glandular, stromal and vascular compartments in implantation stage endometrium following fumagillin treatment actually caused from associated decline in progesterone concentration in peripheral circulation. It is also possible that fumagillin, an angiostatic agent, affects the synthesis and secretion of cytokines primarily in the vascular compartment of implantation stage endometrium, and thereby manifests differential responses in epithelial, stromal and vascular compartments.

Morphometrie study of GnRH analogue, HMG and HCG effects on infrastructure of human endometrial glandular epithelium in early luteal phase

GnRH analogue, HMG and HCG administration are common protocol for ovulation induction in assisted reproductive technology [ART]. Since implantation rate in stimulated ART cycles is lower than unstimulated cycles and as endometrium plays an important role in embryo receptivity, effect of this protocol on the ultrastructure of human endometrial glandular epithelium was studied at LH 4 [embryo transfer time]. In this research endometrial biopsies were obtained from fertile women as well as infertile women who had undergone this protocol at LH 4. Quantitative and qualitative studies on endometrial glandular epithelium was performed by transmission electron microscopy [TEM] and morphometry and the results were statistically compared between the two groups. Qualitative results revealed presence of nuclear channel system [NCS], sub vacuole of glycogen and giant mitochondria [GM] in both groups. Similarly, in quantitative analysis, the volume fractions [Vv] of glycogen, mitochondria and rough endoplasmic reticulum to cell and also the Vv of euchromatin to nucleus were statistically not different [P> 0.05]. These results suggest that ovulation induction by GnRH analogue, HMG and HCG are not associated with advanced endometrial development and consequently, embryo transfer at this stage [before advanced endometrial development which occurs normally at LH 7 to LH 10] may cause a lower rate of implantation

Effect of human follicular fluid on implantation of mouse embryo

Prevention of implantation is considered as one of the suitable methods for contraception or interception. Therefore during this study the effect of human follicular fluid [FF] on mouse implantation was evaluated. The results obtained during this study show that FF contains enzymes and upon incubation with mouse uterine tissue, results in delimitation of epithelium. This effect was inhibited by heat inactivation or addition of EDTA to FF. In vivo uterine wash with follicular fluid on days 3,4,5 and 6-post mating prevents implantation and therefore significantly reduces implantation and pregnancy rate. However uterine wash on day 7 post mating with FF had no effect on implantation and pregnancy rate. On day 3,4,5,6 and 7 with Ham's 10 as control had no effect on implantation or pregnancy rate. Addition of EDTA also prevented the in vivo effect of FF, suggesting that the active agent present in FF is likely to be a metalloprotoinase which inactivates with heat and addition of EDTA. Taking into consideration the fact that FF does not affect the pregnancy of the next cycles, thus the FF or its active agent can be considered as good interceptive agent for prevention of pregnancy rate

Effect of dexamethasone on implantation and pregnancy in albino rats.

Administration of 3 mg/kg body weight of dexamethasone from day 1 or 3 to 7 of pregnancy did not prevent implantation in albino rats. But the same dose when administered from day 8 to 11 resulted in complete abortion / resorption in all rats. Administration of 2 mg / kg body weight of dexamethasone from day 8 to 11 of pregnancy held no effect on the foetal survival. The results indicate that a high dose of dexamethasone does not affect implantation but the same dose affects the more advanced stages of pregnancy.

Anti-implantation effect of a bone-marrow cytokine-BIM.

Successful implantation of blastocyst is dependent upon a cytokine induced localized immunosuppression at uterus. BIM, a bone marrow secreted bio-immunomodulator (BIM) has been observed to have positive immunomodulatory activity in immunosuppressed cases. As pregnancy is associated with immunosuppression upregulation of the suppressed immune system by injection of BIM (conc. 0.08 microg/g b.wt once in rats b.wt. <150 gm or 0.2 microg/g b.wt thrice in rats weighing > 160 gm) is believed to prevent implantation. The anti-implantation action of BIM is probably mediated via mononuclear cells at site of uterus, the effect is reversible and a single dose did not affect the estrous cycle. Multiple dose of BIM however, produce prolonged diestrous and this is probably an autonomic phenomena.

Effect of CDRI-85/287, a potent antiimplantation agent on uterine endometrial dimensions and peroxidase levels in rat.

CDRI compound 85/287 a potent estrogen antagonist and antiimplantation agent in rat was studied to elucidate its mechanism of action. In ovariectomized rats 85/287 treatment antagonized estrogen stimulated uterine volume density, eosinophil leucocyte infiltration, stromal mitotic cell number and peroxidase activity. In parallel experiments in pregnant rats, uterine peroxidase activity also decreased significantly as compared to controls on day 5 post-coitum. The results show that 85/287 exerts its antiimplantation activity by inhibition of responses to estradiol action.

Hormonal requirement for blastocyst implantation and a new approach for anti-implantation strategy.

There is a growing awareness of a need for developing novel methods of contraceptive technology which should not only be effective in providing protection against conception but also take into consideration the reproductive health issues confronting men and women. This paper considers the process of embryo implantation as one such potential target. The hormonal basis of embryo implantation in primates has been discussed to indicate that progesterone, and not estrogen, from ovarian source is the primary determinant of embryo-endometrial maturation and their synchronization for implantation. Thus, low dose administration of the anti-progesterone, mifepristone, during early luteal phase has been shown to be an effective anti-implantation approach to for fertility control. Furthermore, the dissociation of endometrial-hormonal synchrony at the time of blastocyst implantation following the post-ovulatory mifepristone administration has been shown to be the physiological basis of its anti-implantation effect with undisturbed circulatory hormone profiles and ovarian functions. Further studies are required to appreciate the full potential and to mollify the limitations of this approach.

Luteal phase contraception with mifepristone (RU 486) in the rhesus monkey.

Mifepristone (RU 486), an antiprogesterone, is a promising luteal phase contraceptive agent for human use. However, at present its use is limited by the practical constraint of determining the day of ovulation for an LH + 2 day administration of the drug as indicated from experimental and clinical studies. The aim of the present study was to identify the effective period of luteal phase (luteal phase window) when a single administration of mifepristone would induce antinidatory activity without disturbing menstrual cyclicity and ovulatory pattern in the rhesus monkey. RU 486 (2 mg/kg body weight in benzyl benzoate/olive oil, 1:3) was given to mated monkeys (n = 9) on cycle day 16 in the first treatment cycle (treatment group T1, n = 9), and in the following cycle on cycle day 20 (treatment group T2, n = 8). A single s.c. injection of this antiprogestin during early to midluteal phase (days 1-10 after ovulation, as determined from retrospective analysis of serum concentrations of estrogen and progesterone) provided a one hundred per cent protection against pregnancy, with no apparent side effects. There were no changes in cycle lengths (F = 3.5; P < 0.3), day of ovulation (F = 1.8; P < 0.7) and duration of menses (F = 3.5; P < 0.3) compared with the pre-treatment and post-treatment cycles. Pooled analyses of serum concentrations of estrogen and progesterone during luteal phases of T1 and T2 cycles also showed no variations with those in pre- and post-treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Need of dietary energy at critical implantation time when local ovarian hormones are obligatory for conceptus development.

Role of dietary energy and local ovarian hormones in conceptus development in the rat was evaluated by giving ip injections of estrogen and progesterone under diet restricted and/or dextrose supplemented conditions, using the experimental model of ovarian compensatory hypertrophy. Replacement of estrogen on day 2 and progesterone on day 3 was necessary for conceptus development in the ipsilateral uterine horn after unilateral ovariectomy on day 2. Continuation of progesterone injection up to day 9 improved the percentage of conceptus development. Conceptus development was normal when unilateral ovariectomy was performed after day 2 of pregnancy. Compensatory increases in corpus luteum (CL) volume and the activity of delta 5 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD) in contralateral ovary were observed after unilateral ovariectomy on day 2-4 of pregnancy. However, 70% diet restriction reducing the energy intake (from 90 to 27 kcal/rat/day) abolished the single dose hormone therapy effects in ipsilateral horn conceptus development and also reduced the effects of continued progesterone, percentage of contralateral horn conceptus development, compensatory changes in the CL volume and delta 5 3 beta-HSD activity of the contralateral ovary. However, dietary dextrose supplementation (increasing calorie intake from 27 to 56 kcal/rat/day) significantly improved/restored hormone response for conceptus development, compensatory changes of the CL volume and enzyme activity in contralateral ovary. The results suggest that day 2-3 of pregnancy is the critical time when local ovarian supply of estrogen and progesterone are obligatory for establishment and conceptus development in the rat. During this period adequate mobilizable source of energy is necessary for execution of hormonal message.