Verbena officinalis is widely used by women for maintaining general health and treating various gynaecological disorders during pregnancy. A case report has indicated that the consumption of V. officinalis induced an abortifacient effect. Hence, this study aimed to investigate the prenatal developmental toxicity of this plant according to OECD guideline (no. 414). A total of 50 pregnant female rats (dams) were distributed into five groups (n = 10); 500 mg/kg 1000 mg/2000 mg/kg and 3000 mg/kg of V. offcinalis extracts and the fifth group served as a normal control. All dams received their respective oral single daily treatment from the 6th to the 20th day of gestation. Maternal clinical toxicity signs, body weight and weight gain were recorded. Caesarean sections were performed on day 21 to evaluate embryo-foetal developmental toxicity. For dams, ovaries were harvested and weighed. The number of corpora lutea, implantation sites, and resorptions were recorded. No mortality was observed in dams, but their body weight gain was significantly reduced particularly in dams treated with 2000 and 3000 mg/kg V. officinalis. Asymmetrical distribution of implantation sites and embryos were observed. Embryo-fetotoxicity retardation was observed as evident by the decrease in foetal weight, head cranium, tail length, and higher incidence in the pre-and post-implantation loss. Some foetal skeleton abnormalities such as incomplete ossification of skull, sternebrae, and metatarsal bones were observed in foetuses of the 2000 and 3000 mg/kg V. officinalis-treated dams. LC/MS analysis identified the major constituents including geniposidic acid, tuberonic acid glucoside, luteolin 7, 3'-digalacturonide, iridotrial and apigenin. The glycosylated flavonoids such as apigenin and luteolin could be responsible for the reported prenatal developmental toxicity. In conclusion, the use of V. officinalis during pregnancy is not safe indicating evidence-based toxic effects on the reproductive performance of dams and dose-dependent risk potentials to the foetuses.
Traditionally Plumbago rosea L. is used as an abortifacient in the Southeast Asian region. Methanolic root extract of a local species of Plumbago rosea L. was studied to evaluate its traditional antifertility claim. Interestingly, it was found to possess dose related inhibitory effect on uterine contractile responses elicited by oxytocic agents on isolated uteri of pregnant and pseudo-pregnant rats. Furthermore, it was found to possess significant (p < 0.05) fetotoxic activity along with mild abortive potential in pregnant mice when given orally at high doses (400 and 800 mg kg(-1)) once daily for ten days starting from day 10 of gestation. The results derived indicated possible presence of utero-active compound (s) in this plant that inhibited oxytocic agents induced uterine motility. Moreover, pronounced fetotoxic and mild abortifacient potentials observed at higher doses in pregnant mice might support its accredited traditional use to avoid unwanted pregnancy.
A malignancy discovered in pregnancy is often difficult to manage; the optimal maternal therapy has to be balanced with the fetal well-being. Generally, the cancer is managed as though the patient is not pregnant. For the various site-specific cancers, surgery is the main modality of treatment; this should be individualized. Chemotherapeutic agents are highly teratogenic in the first trimester, with some adverse effects when used after 12 weeks' gestation. The overall survival rate for pregnancy-associated breast cancer is poor; the reasons for this are discussed. For cervical cancer, delivery by caesarean section appears to be the method of choice, with significantly better survival rates compared with those who deliver vaginally. Other gynaecological and non-gynaecological malignancies are discussed.
The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.