Ex-vivo abortifacient activity of Androsace foliosa n-hexane leaves extract on isolated rabbit uterus.

Androsace foliosa is a medicinal herb utilized in different areas of Pakistan for abortifacient, diabetic and liver complications. In the current research, the possible action of the n-hexane leaves extract of the Androsace foliosa on isolated rabbit uterus was examined. Abortifacient activity was examined in the existence of standard antagonist e.g. atropine and salbutamol and a uterine tonic like oxytocin. The isolated rabbit uterus is initially treated with 1mg/kg stilboesterol for 1 complete day. The consequence of oxytocin as uterine contraction agonist was observed. Additionally, antagonists e.g. salbutamol (2µg) and atropine (1-2mg) on the uterine contractile action of the extract were also examined. The A. foliosa n-hexane leaves extract fashion dose correlated amplification in the force of uterine contraction comparable to oxytocin. The drug oxytocin was pragmatic to amplify the uterine contractile action of the extract. Meanwhile pre-treating the tissue with either atropine or salbutamol earlier than administrating the extract indicates the inhibitory action of the drugs on the action of the extract.

Early medical abortion with self-administered low-dose mifepristone in combination with misoprostol.

AIM: The aim of the present study was to investigate the safety and efficacy of low-dose mifepristone combined with self-administered misoprostol for termination of early pregnancy. METHODS: A total of 533 women seeking medical abortion in early pregnancy (≤49 days since the last menstrual period) were divided randomly into hospital- (H-Mis, 250) and self- (S-Mis, 283) administered misoprostol groups. Women in two groups took 100 mg of oral mifepristone in hospital followed by 200 µg of sublingual misoprostol 24 h later in hospital or home. The primary outcome parameter was complete abortion without surgical intervention. Secondary outcomes were uterine bleeding, return of regular menses, side effects and patient acceptability. RESULTS: High rates of complete abortion were observed for both the H-Mis group (243/250; 94.8%) and the S-Mis group (266/283; 94.0%). No significant differences in outcomes (complete abortion/failure rates) or side effects were observed between the two groups. General satisfaction rates were similar for the two groups (H-Mis, 231/250, 92.4%; S-Mis, 263/283, 92.9%; P > 0.05). Higher convenience of administration (H-Mis, 211/250, 84.4%; S-Mis, 270/283, 95.4%; P < 0.05) and privacy protection (H-Mis, 214/250, 85.6%; S-Mis, 267/283, 94.3%; P < 0.05) satisfaction rates were obtained for the S-Mis group than for the H-Mis group. CONCLUSION: Self-administered sublingual misoprostol is as safe and effective as hospital-administered misoprostol following low-dose mifepristone to terminate early pregnancy (≤49 days of amenorrhoea) with fewer side effects.

Abortifacient metapristone (RU486 derivative) interrupts CXCL12/CXCR4 axis for ovarian metastatic chemoprevention.

Recent global epidemiological studies revealed the lower ovarian cancer death from long-term use of oral contraceptives. However, the underlying mechanism of action is not clear. Here, we use the abortifacient metapristone (RU486 derivative) to test the hypothesis that the contraceptives might interrupt CXCL12/CXCR4 chemokine axis to inhibit ovarian cancer metastasis. Metapristone at concentrations (

Functional implications of the utero-placental relaxin (RLN) system in the dog throughout pregnancy and at term.

Relaxin (RLN) is a key hormone of pregnancy in mammals best known for its involvement in connective tissue remodeling. In the domestic dog, placental RLN is the only known endocrine marker of pregnancy. However, knowledge is sparse regarding the spatio-temporal expression of RLN and its receptors (RXFP1 and RXFP2) in the canine uterus and placenta. Here, their expression was investigated in the pre-implantation uterus and utero-placental compartments (UtPl) at selected time points during gestation: post-implantation, mid-gestation, and at normal and antigestagen-induced luteolysis/abortion. Immunohistochemistry with newly generated, canine-specific antisera, in situ hybridization and semi-quantitative PCR were applied. In compartmentalization studies, placental and endometrial RLN increased continuously toward prepartum. The placental RXFP1 was time-related and highest during post-implantation and decreased together with RXFP2 at prepartum luteolysis. The endometrial levels of both receptors did not vary greatly, but myometrial RXFP2 decreased from mid-gestation to prepartum luteolysis. Antigestagen treatment resulted in suppression of RLN in UtPl and decreased RXFP1 and RXFP2 in the uterus. The placental RLN was localized mainly in the cytotrophoblast. Additionally, RXFP1 stained strongly in placental endothelial cells while RXFP2 was found mainly in maternal decidual cells. Uterine staining for all targets was found in epithelial cellular constituents and in myometrium. Finally, besides its endocrine functions, RLN seems to be involved in auto-/paracrine regulation of utero-placental functions in dogs in a time-dependent manner. New insights into feto-maternal communication was provided, in particular regarding the localization of RXFP2 in the maternal decidual cells, implying functional roles of RLN during the decidualization process.

A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients.

In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches.

"In patient" medical abortion versus surgical abortion: patient's satisfaction.

OBJECTIVE: To compare patients' satisfaction with medical and surgical abortion, implementing the Italian guidelines on medical abortion entailing an "in patient" procedure. METHODS: A total of 1832 pregnant chose between surgical (vacuum aspiration) or medical abortion (mifepristone p.o. followed after 3 days by sublingual misoprostol) and expressed their expected satisfaction on a visual analog scale (VAS). A total of 885 women chose surgical and 947 medical abortion. The primary end-point was satisfaction VAS score 20 days after the procedure. Secondary end-points were: difference between pre- and post-abortion VAS score; difference in satisfaction VAS scores according to parity and previous abortion; incidence of side effects. RESULTS: VAS score was high in each group but significantly higher for the 1-day surgical than for the 3-day medical abortion procedure (7.9 ± 1.0 versus 7.2 ± 1.2; p < 0.0001). In the surgical group the VAS score increased after the treatment (6.9 ± 1.6 versus 7.9 ± 1.0, p < 0.0001), while it decreased in the medical group (7.5 ± 1.0 versus 7.2 ± 1.2; p < 0.0001). Multiparous women reported higher satisfaction with medical abortion; women with a previous abortion preferred surgical abortion. CONCLUSIONS: Both procedures are considered satisfactory by the patients. Performing medical abortion as a 3-day "in patient" procedure, decreased women's satisfaction scores from their baseline expectations.

Unsafe abortion in rural Tanzania - the use of traditional medicine from a patient and a provider perspective.

BACKGROUND: The circumstances under which women obtain unsafe abortion vary and depend on the traditional methods known and the type of providers present. In rural Tanzania women often resort to traditional providers who use plant species as abortion remedies. Little is known about how these plants are used and their potential effect. METHODS: Data were obtained among women admitted with incomplete abortion at Kagera Regional Hospital during the period January - June, 2006. The women underwent an empathetic interview to determine if they had experienced an unsafe abortion prior to their admission. In all 125/187 women revealed having had an unsafe abortion. The women identified as having had an unsafe abortion underwent a questionnaire interview where information about abortion provider and abortion method used was obtained through open-ended questions. To get more detailed information about the traditional methods used to induce abortion, in-depths interviews and focus group discussions were performed among traditional providers and nurses. Finally, the plant specimen's effectiveness as abortion remedies was assessed through pharmacological analyses. RESULTS: Among women admitted with incomplete abortions, 67% had had an unsafe abortion. Almost half of the women who had experienced an unsafe abortion had resorted to traditional providers and plant species were in these cases often used as abortion remedies. In all 21 plant species were identified as potential abortion remedies and analysed, 16 of the species were found to have a uterine contractive effect; they significantly increased the force of contraction, increased the frequency of contractions or did both. CONCLUSION: Unsafe abortion is common in rural Tanzania where many women use plant species to terminate an unwanted pregnancy. The plants have a remarkable strong uterine contractive effect. To further understand the consequences of unsafe abortion there is a need for further analyses of the plants' potential toxicity and mutagenicity.

The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta.

STUDY QUESTION: What is the effect of letrozole on the expression of steroid receptors in the placentae in cases of termination of pregnancies? SUMMARY ANSWER: The expression of estrogen receptor-α (ERα) and progesterone receptor (PR) transcripts, as well as ERα protein, in placentae was suppressed by letrozole pretreatment in second trimester termination of pregnancy. WHAT IS KNOWN ALREADY: There have been no data in the literature on the effect of letrozole in termination of human pregnancies. STUDY DESIGN, SIZE, DURATION: This study is part of a clinical randomized trial in which 50 subjects were recruited and 44 placentae were collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women (n = 50) requesting second trimester abortion between 12 and 20 gestational weeks were randomized to receive either letrozole or placebo pretreatment for 3 days before administration of vaginal misoprostol. Placentae were collected from both groups of women after the abortion. Total RNA from the frozen placenta samples was extracted and subjected to real-time RT-PCR analysis of ERα and estrogen receptor-ß (ERß), PR and glucocorticoid receptor (GR) transcripts. Immunohistochemical studies of ERα, ERß, PR and GR expression, as well as Ki67 and PCNA staining for proliferation, were performed. TUNEL assays were performed to determine the extent of apoptosis. MAIN RESULTS AND THE ROLE OF CHANCE: Real-time RT-PCR demonstrated that the median ERα {3.900 [95% confidence interval (CI): -0.643-8.443] in the letrozole group versus 4.714 (95% CI: 1.776-7.652) in the control group; P = 0.005} and the median PR [0.701 (95% CI: 0.333-1.069) in the letrozole group versus 1.774 (95% CI: 1.07-2.478) in the control group; P = 0.003] were significantly lower in the letrozole group compared with the control group. Furthermore, ERα protein levels, in both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells, were significantly reduced [H-score of 113 (95% CI: 103-119) in the letrozole group versus 217 (95% CI: 214-290) in the control group, in syncytiotrophoblasts; 100 (95% CI: 98-105) in the letrozole group versus 210 (95% CI: 200-286) in the control group, in cytotrophoblasts; P = 0.004], while the expression levels of ERß, PR, GR, PCNA, Ki67 and TUNEL were not significantly different between the two groups. LIMITATIONS, REASONS FOR CAUTION: Only the placentae from the second trimester termination of pregnancy were collected in this study. Information from first trimester terminations is still lacking. WIDER IMPLICATIONS OF THE FINDINGS: The results shed some light on the mechanism of action of letrozole pretreatment in termination of pregnancies. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the GRF/RGC and CRCG grants of the University of Hong Kong. TRIAL REGISTRATION NUMBER: HKClinicalTrials.com with trial number HKCTR-695.

Efficacy of Ginkgo biloba on vaginal estrous and ovarian histological alterations for evaluating anti-implantation and abortifacient potentials in albino female mice.

Ginkgo extract, EGb 761 is known as a vasoregulatory variable for the conventional reproduction therapy. EGb 761 was orally administered in 0 (control), 3.7, 7.4, and 14.8 mg/kg bw/day for 28 days (thereafter mated with normal fertile male), from day 1 to day 7 of pregnancy or from the 10th to 18th day of pregnancy, respectively. Vaginal smears were performed daily. On 20th day of pregnancy, the females were killed by cervical dislocation and their kidneys, liver, brain, placenta, spleen and ovaries were removed and weighed. The ovaries were prepared for histological examinations, and then ovarian follicles were counted. Maternal toxicity, estrous cycle, reproductive hormones, ovarian follicle counts, resorption index, implantation index, fetal viability and fetuses, and placenta mean weights were evaluated. There was a dose-dependent ovarian toxic effect of EGb 761. Ovarian follicle counts, resorption index, implantation index, fetal viability were significantly reduced in 14.8 mg/kg bw/day dose. Treatment with 14.8 mg/kg bw/day EGb 761 induced disruption of estrous cycle and caused maternal toxicity, in addition to fetal toxicity. Therefore, the data obtained indicate that Ginkgo biloba extract at 14.8 mg/kg bw/day dose level exhibit toxic effect on reproductive cyclicity and could have anti-implantation and abotifacient properties in female mice.

Efficacy of cloprostenol or aglepristone at 21-22 and 35-38 days of gestation for pregnancy termination in queens.

The objective of this study was to evaluate the efficacy of cloprostenol (CLO) or aglepristone (ALI) for pregnancy termination in queens at 21-22 and 35-38 days of gestation. Two experiments (EXP) were carried out to accomplish this aim. Thirty-seven 12- to 14-month-old mixed breed queens were used in a randomized design. At oestrus, queens were housed for mating with a tom, and pregnancy was confirmed by transabdominal ultrasonographic examination (US). On days 21-22 of pregnancy (EXP1) or 35-38 of pregnancy (EXP2), queens were divided into three groups (G). Queens in G1 received ALI (10 mg/kg, sc; EXP1, n = 6; EXP2, n = 6) on two consecutive days. Queens in G2 received CLO (5 µg/kg, sc; EXP1, n = 6; EXP2 = 7) on three consecutive days. Queens in G3 received 1 ml of saline solution (PLA, sc; EXP1, n = 6; EXP2 = 6). After treatment, females were monitored daily by US during for 10 days and weekly until the end of gestation. In EXP1, pregnancy was terminated in (6/6, 100%), (0/6, 0%) and (0/6, 0%), for the ALI, CLO and PLA groups, respectively (p < 0.001). In EXP2, pregnancy was terminated in (6/6, 100%), (1/7, 14%) and (0/6, 0%) for the ALI, CLO and PLA groups, respectively (p < 0.001). In both EXP, after CLO administration, animals vomited and were depressed for 30 min; but no side effects were observed in the animals in the ALI group. In conclusion, the results from this study indicate that three injections of CLO are not effective, but two injections of ALI are effective to induce abortion in queens at 21-22 or 35-38 days of pregnancy.

Clinical Update on Uses for Mifepristone in Obstetrics and Gynecology.

Importance: Mifepristone (RU-486) is a selective progesterone receptor modulator that has antagonist properties on the uterus and cervix. Mifepristone is an effective abortifacient, prompting limitations on its use in many countries. Mifepristone has many uses outside of induced abortion, but these are less well known and underutilized by clinicians because of challenges in accessing and prescribing this medication. Objectives: To provide clinicians with a history of the development of mifepristone and mechanism of action and safety profile, as well as detail current research on uses of mifepristone in both obstetrics and gynecology. Evidence Acquisition: A PubMed search of mifepristone and gynecologic and obstetric conditions was conducted between January 2018 and December 2021. Other resources were also searched, including guidelines from the American College of Obstetricians and Gynecologists and the Society of Family Planning. Results: Mifepristone is approved by the Food and Drug Administration for first-trimester medication abortion but has other off-label uses in both obstetrics and gynecology. Obstetric uses that have been investigated include management of early pregnancy loss, intrauterine fetal demise, treatment of ectopic pregnancy, and labor induction. Gynecologic uses that have been investigated include contraception, treatment of abnormal uterine bleeding, and as an adjunct in treatment of gynecologic cancers. Conclusions and Relevance: Mifepristone is a safe and effective medication both for its approved use in first-trimester medication abortion and other off-label uses. Because of its primary use as an abortifacient, mifepristone is underutilized by clinicians. Providers should consider mifepristone for other indications as clinically appropriate.

Network pharmacology-based study on immunomodulatory mechanism of danggui-yimucao herb pair for the treatment of RU486-induced abortion.

ETHNOPHARMACOLOGICAL RELEVANCE: The Danggui-Yimucao herb pair (DY) is a classic combination in Chinese herbal formulas, consisting of the root of Angelica sinensis (Oliv.) Diels and the aerial parts of Leonurus japonicus Houtt. DY first appeared in "Zhulinsi fuke mifang" in the Jin Dynasty, and it has a long history as a drug for the treatment of abortion. However, its underlying immunomodulatory mechanisms involved are still unclear. AIM OF THE STUDY: In this study, network pharmacology and pharmacological experiments were used to explore the role and mechanism of DY in the treatment of medical abortion. MATERIALS AND METHODS: Network pharmacology was used to establish the relationship between the components of DY and abortion-related targets, and to enrich important pathways and biological process for verification. ELISA was used to assess progesterone levels. Flow cytometry was used to detect the degree of differentiation of Th1/Th2 cells. Immunohistochemical methods and qPCR were used to measure the expression levels of T-bet, GATA-3 and IL-4. RESULTS: Through the prediction analysis of network pharmacology, we found that key pathway for DY treatment of abortion, such as anemia, pelvic infection, immune disorders, and coagulation disorders, was Th1/Th2 cell differentiation pathway. The pharmacological results revealed that DY greatly corrected the imbalance of Th cell subsets in abortion mice, significantly inhibited the differentiation of Th2 cells, and resulted in an increase in the Th1/Th2 ratio. In addition, the concentration of progesterone in the serum of mice after abortion was significantly reduced. We also found that DY upregulated spleen T-bet and downregulated IL-4 gene expression in mice. Besides, immunohistochemical results showed that DYE could up-regulate T-bet but inhibit GATA-3 expression. CONCLUSIONS: Our results showed that after RU486-induced abortion, progesterone and Th1/Th2 paradigm were disordered in mice, but DY could make mice recover more quickly, which indicated that DY had great development value in immunoregulation.

CyPPA, a positive modulator of small-conductance Ca(2+)-activated K(+) channels, inhibits phasic uterine contractions and delays preterm birth in mice.

Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca(2+)-activated potassium channels (K(Ca)2), specifically isoforms K(Ca)2.2 and 2.3, may control these contractions through negative feedback regulation of Ca(2+) entry. We tested whether selective pharmacologic activation of K(Ca)2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both K(Ca)2.2 and K(Ca)2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the K(Ca)2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective K(Ca)2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC(50) 5.33 ± 0.09, 4.64 ± 0.03, 4.72 ± 0.10, respectively), all contractions were abolished between 30 and 60 µM. Blunted contractions were associated with CyPPA depression of spontaneous Ca(2+) events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F(2α) did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial K(Ca)2.2/2.3 channels effectively suppresses Ca(2+)-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies.

Defining reality: the potential role of pharmacists in assessing the impact of progesterone receptor modulators and misoprostol in reproductive health.

Medical abortion is increasingly heralded as an ideal method for decreasing maternal mortality in health-care resource-deprived areas and as an answer to the shrinking pool of physicians willing to perform abortions. The advent of progesterone receptor modulators (PRMs) and the recent approval by the Food and Drug Administration of ella (ulipristal) as an emergency contraceptive put pharmacists in the center of abortion controversy. Pharmacists, worldwide, need to be aware of the controversy surrounding the introduction of PRMs, particularly with regard to the effect on health policy, their mechanism of action, associated adverse events, and common off-label uses. Once understood, genuine opportunity exists for pharmacists to serve a fundamental role in positively shaping public health policy.

Partial foetal retention following aglepristone treatment in a bitch.

This short communication describes the case of partial foetal retention in an 18-month-old female French bulldog following induction of abortion owing to an undesired mating. Abortion was induced with aglepristone administered in two consecutive protocols of a dual injection 1 day apart. After failure of the first treatment to achieve abortion, 15 days later, a second treatment was administered. Delivering of aborted foetus occurred 2 days after the last administration. Five weeks after the abortion, the female showed a weak haemorrhagic vaginal discharge. On ultrasound examination, the presence of uterine wall distension as well as a puppy skull inside the uterus was observed. This clinical case makes clear that although aglepristone is a very reliable drug, follow-up of the female during treatment and in the immediate post-partum is necessary to ensure a good outcome.

Expression and activity of matrix metalloproteinases in the uterus of bitches after spontaneous and induced abortion.

Aim of this study was to determine the intrauterine activity of matrix metalloproteinases (MMP)-2 and -9 after cessation of the local effect of progesterone. For this purpose, pregnancy was terminated in 10 bitches at mid-gestation with the progesterone receptor antagonist aglepristone (10 mg/kg body weight, sc, Alizine®; Virbac, France) at two subsequent days (group IRA = induced resorption/abortion). The IRA group was divided into two subgroups (Group I, n = 5, days 25-35 of pregnancy; group II, n = 5, days 36-45). Five further bitches were introduced with beginning abortion (group SRA = spontaneous resorption/abortion). Seven healthy bitches between day 25 and 45 of gestation served as controls. After ovariohysterectomy at the end of abortion and between days 25 and 45 of gestation, respectively, the distribution and activity of collagenases were investigated by immunohistochemistry and gelatin zymography. At placental sites, MMP-2 activity in the endometrium was significantly lower in IRA groups than in the SRA group (33.7 ± 11.8% and 39.3 ± 5.4% vs 52.2 ± 10.2%, p < 0.05); however, MMP-2 expression was lowest in the control group (control: 21.4 ± 6.3%; p < 0.01) and similarly in the myometrium (controls: 13.1 ± 2.5%; p < 0.05). MMP-9 activity was also lower in the endometrium and myometrium of the control group in comparison to SRA and IRA groups (11.8 ± 3.2%; p < 0.01 and 28.4 ± 32.8%; p < 0.05). At interplacental sites, the amount of active collagenases in the myometrium was significantly lower in the control group. It is concluded that the blockade of the biological progesterone effect was associated with an increase in activity of both collagenases.

Ananas comosus: is the unripe fruit juice an abortifacient in pregnant Wistar rats?

OBJECTIVE: The juice of unripe pineapple (Ananas comosus) was investigated for abortifacient activity in pregnant Wistar rats. METHOD: Animals in Groups A, B, C and D received orally 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the juice, respectively, once daily from day 7 until day 14 of pregnancy. RESULTS: The juice contained tannins, cardenolides, dienolides, cardiac glycoside and flavonoids. The number and weights of live fetuses, number of implantation sites, corpora lutea, computed percent implantation index, resorption index, pre- and post-implantation losses were not significantly (p > 0.05) altered. Neither fetal death, nor provoked vaginal bleeding was observed in the pregnant rats. The maternal weight increased in all the experimental animals with that of the control augmenting least. The 250 and 500 mg/kg body weight dosages increased (p < 0.05) the serum concentrations of progesterone and oestrogen in the pregnant rats. CONCLUSION: The fruit juice of Ananas comosus does not exhibit abortifacient activity in pregnant Wistar rats.

Azadirachta indica A. Juss (neem) as a contraceptive: An evidence-based review on its pharmacological efficiency.

BACKGROUND: Azadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action. PURPOSE: The present review aims to summarize the efficiency of A. indica treatment as a contraceptive. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. RESULTS: A total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 2005 and 2009. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles. CONCLUSION: Although A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive.

Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention.

BACKGROUND: The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. METHODS: Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17ß-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. RESULTS: Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17ß-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. CONCLUSIONS: The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.