scholarly journals Effects of Maternal Exposure to Lamotrigine during Pregnancy on Gonadal Toxicity in Fetus Rats

2020 ◽  
Vol 9 ◽  
pp. 1557
Author(s):  
Hoda Aryan ◽  
Shabnam Movassaghi ◽  
Amir Ghasemi ◽  
Roksana Darabi

Background: Lamotrigine is one of the newest antiepileptic drugs that is used as one of the most common treatments in pregnancy. Since the investigation of the teratogenic effects of lamotrigine is very limited and there is no report of its teratogenic effects on fetal gonads, we aimed to investigate the teratogenic effects of lamotrigine on embryonic gonads. Materials and Methods: This study was performed on nine female Wistar female rats (8 weeks, weighing 180-200 mg). At first, the animals were inspected regularly by the preparation of vaginal smear and in the estrus phase in separate cages of mating, and after observing the vaginal plaque, were randomly divided into three groups (n=3). Control group did not receive any treatment.  In the lamotrigine group (20mg/kg), and the vehicle group (same volume of normal saline) were injected intraperitoneally from days 8 to 13 of pregnancy. On day 20, animals were anesthetized by sodium pentobarbital (40 mg/kg), and embryos were extracted through laparotomy. First, fetuses were weighed, and their height (crown-rump length) was measured. Then the gonads of the fetuses were removed and, stained with H & E, and examined by optical microscope. Results: Our results showed that in the lamotrigine group, the number of seminiferous tubules and Sertoli cells in the male embryos and the number of oocytes in the female embryos decreased significantly compared to the control and vehicle groups (P≤0.05). Conclusion: The results of this study showed that treatment with 20 mg/kg lamotrigine in mothers during pregnancy could cause damage to fetal gonads. [GMJ.2020;9:e1557]

2015 ◽  
Vol 6 (2) ◽  
pp. 67-72
Author(s):  
Manizheh Karami ◽  
Fatemeh Lakzaei ◽  
MohammadReza Jalali Nadoushan

ABSTRACT Background and objective Polycystic ovary syndrome (PCOS) can be induced in Wistar rats by over production of nitric oxide (NO). This study evaluated the efficacy of naloxone on the breeding characteristics of rats suffering from nitric oxide induced PCOS. Materials and methods Twenty-four female Wistar rats(200–250 gm) were kept as virgin under standard conditions. They were divided into four groups (n = 6). One group of the animals received L-arginine (50 mg/kg) intraperitoneally (i.p.) for 9 days/once a day. Another group was administered naloxone hydrochloride (0.4 mg/kg, i.p.) prior to injection of L-arginine. The third group was injected solely naloxone. Control group received saline solution (1 ml/kg, i.p.). After the treatments, all female rats were coupled with the intact males. They were then separated by observation of vaginal plaques; it was considered as day 0 of pregnancy. Eventually, they were operated on days 18 to 19 of the gestation to collect the animals’ ovaries. The samples were studied for pathological evidence. The fetal number and weight along with the fetal crown-rump length (CRL) were measured. Results The ovaries obtained from the L-arginine treated group had large cysts with thickened granulosa cell layer in contrast to those of the control or naloxone treated rats (p < 0.0001). The number of fetus though showed a decrease in the L-arginine treated rats (3 ± 1), but the fetal weight or fetal CRL did not change (p > 0.05). Conclusion This study may clearly illustrate the polycystic characteristics in the L-arginine treated group. It may particularly display the breeding efficacy of naloxone in rats with PCOS. How to cite this article Karami M, Lakzaei F, Nadoushan MRJ. Naloxone Breeding Effectiveness in Rat Suffering from Nitric Oxide-induced Polycystic Ovary Syndrome. Int J Infertil Fetal Med 2015;6(2):67-72.


2021 ◽  
Vol 14 (3) ◽  
pp. 1267-1279
Author(s):  
Dharmender Sharma ◽  
Gurinder Kaur Sangha

Traditional therapeutic procedures using antioxidant-rich fruits and vegetables have been in vogue for the development of evidence-based biomarkers for assessing reproductive health. Present investigation was designed to study the antioxidative potential of broccoli sprouts aqueous extract (BE), against ovarian toxicity in female rats induced by triazophos (TZ). In the experimental setup, six groups of rats were formed; Control (group 1), BE (group 2), TZ (group 3), and also BE+TZ groups such as BE1 (group 4), BE2 (group 5) and BE3 (group 6) groups. Body weight was weekly recorded of all the rats, while vaginal smear was observed daily during 30 days experiment. After sacrifice, oxidative stress (OS) biomarkers levels viz; catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and lipid peroxidation (LPO) were determined along with histopathological and apoptotic observation. Results revealed differentially modified changes in OS biomarkers as CAT, SOD, GR, GPx, and GST, while LPO levels were significantly improved with broccoli supplementation compared to TZ group rats. Plasma progesterone and estradiol levels were also restored along with improved ovarian histoarchitecture among all BE+TZ treated rats. Reduced apoptotic granulosa cells with reduced atresia and normal ovarian surface epithelium height were also observed with BE treatment. BE exerts multi-mechanistic protective effects against TZ induced ovarian toxicity which is attributable to its antioxidant and protective actions.


2018 ◽  
Vol 27 (6) ◽  
pp. 515-522 ◽  
Author(s):  
Atilla Karateke ◽  
Recep Dokuyucu ◽  
Hatice Dogan ◽  
Tumay Ozgur ◽  
Zeynel Abidin Tas ◽  
...  

Objective: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. Methods: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. Results: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). Conclusion: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.


Author(s):  
M. P. Soltys ◽  
H. V. Rudyk ◽  
V. M. Gunchak ◽  
B. V. Gutyi

The effect of ‘Vitosept’ drug, based on sodium hypochlorite solution with high purity, obtained in a specially developed membraneless flow electrolyzer, on the embryotoxic and teratogenic properties in rats was investigated. To determine the embryotoxic effect of ‘Vitosept’ on the development of white rats offspring of the 1st generation, control and three experimental groups (G1, G2, G3) were formed from pregnant females. The females of the control group with a blunt probe were injected daily for 30 days with 5 ml of isotonic sodium chloride solution, and experimental ones with 5 ml of ‘Vitosept’ drug with different concentration of high purity sodium hypochlorite: Group I (G1) — 50 mg/l; Group II (G2) — 100 mg/l; Group III (G3) — 500 mg/l. The animals were observed. During the observation the condition and behavior of the females, the dynamics of body weight change, duration of pregnancy, and the course of birth were monitored. The results of the experiment were recorded after the slaughter of pregnant females (20th day of pregnancy) and in the postnatal period of development of the offspring. Studies have shown that the use of different concentrations of the drug ‘Vitosept’ in rats for 30 days before and during pregnancy has no embryotoxic and teratogenic effects. According to the indicators of the total, pre- and postimplantation lethality of embryos, there were no reliable changes in the structure and morphometry of internal organs and tissues in 20-day-old fetuses, and their development corresponded to the terms of pregnancy. There was no significant difference between the fertility of female rats in the test and control groups. The average number of fetuses per female was within 9 animals. The rats obtained from the females of the experimental groups were viable and did not lag behind in growth and development compared with the control animals, which generally characterizes the studied drug ‘Vitosept’ as non-toxic, lacking embryotoxic and teratogenic action


2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Tatiana V. Palatova ◽  
Alla B. Bucharskaya ◽  
Anna V. Medvedeva ◽  
Elena S. Voronina ◽  
Svetlana S. Pakhomy ◽  
...  

Goal — to assess the effect of antenatal hypoxia of various origins on the morphology and reproductive function of the testes of newborn and mature rats in experiment. Material and Methods — In experiments 15 white outbred female rats aged 4 to 10 months with a weight of 200±30 g were used. Laboratory animals were randomly divided into 2 experimental and 1 control groups, 5 females each. The first group underwent normobaric hypoxia throughout pregnancy (21 days). Hypoxia modeling was conducted in accordance with the method of N.N. Karkishchenko (2010). The second group underwent hemic hypoxia during the second and third week of pregnancy, in accordance with the method of L.M. Sosedova (2012). The third (control) group was not exposed to any effect throughout pregnancy. Results — in the testicles of newborn rats of the experimental groups, the decrease of tubule diameter was observed, the increase of stroma area and development of interstitial edema were noted. In the group of hemic hypoxia, a significant decrease in the number of Leydig cells was noted. In the tissues of the testicles of mature rats, who underwent antenatal hypoxia, a decrease of tubule diameter, a significant decrease in the spermatogenesis index and a decrease of spermatogonia number were noted. The developed damage of spermatogenic epithelium in experimental groups of newborns and mature rats was confirmed by marked expression of the apoptosis marker (Bax), weak expression of proliferation markers (Ki-67) and receptor of receptor of fibroblast growth factor (FGFR). Conclusion — in animals with chronic hypoxia of various origins, there is an inhibition of spermatogenesis and a violation of the spermatogenetic function of the testicular seminiferous tubules.


2018 ◽  
Vol 69 (1) ◽  
pp. 140-143
Author(s):  
Gabi Dumitrescu ◽  
Ioan Pet ◽  
Dorel Dronca ◽  
Mirela Ahmadi ◽  
Liliana Petculescu Ciochina ◽  
...  

The reproductive system of the vertebrates - mainly of the adult males -seems to be vulnerable to the action of endocrine disruptors. The aim of this study was to evaluate the effect of octylphenol (OP) on histological structure of testis in NMRI mice. The mice were divided in three groups (5 mice for each group) such as: control group (C - untreated); vehicle group (V - treated with a mixture of ethanol and corn oil 1:10) and experimental group (E � treated with OP in concentration of 160 mg/kg body weight). The solution of OP was prepared in ethanol, administered by subcutaneous injection in the thigh region (1 ml total volume), for seven consecutive days. For histological examination, after slaughtering, the testes were fixed in 10% neutral formalin, embedded in paraffin, sectioned to a thickness of 5 �m and stained with Mallory�s trichrome method. Microscopic analysis reveals in the individuals from the C and V groups, the normal morphology of the seminiferous tubules. In the case of individuals in the E group, treated with OP, in the testicular parenchyma occurs changes consisting in: detachment of the seminiferous tubule epithelium, mild proliferation of germ cells, the presence of apoptotic bodies among the cells of seminal line, diffuse hyperplasia of the Leydig interstitial cells and hypertrophy of the peritubular capillary. Experimental data obtained in this study demonstrated that the treatment with octylphenol induces irreversible changes in the testicular parenchyma with the disruption of spermatogenesis process.


2017 ◽  
Vol 15 (2) ◽  
pp. 186
Author(s):  
Kurnia Agustini ◽  
Dwi Riani Wulandari ◽  
Lestari Rahayu

Fennel fruit (Foeniculum vulgare Mill.) is one of traditional plant medicine known having effects as anti-infl ammatory, analgesic and antioxidant. It also has been reputed to increase milk secretion, promote menstruation, facilitate birth, alleviates the symptoms of the male climacteric andincrease libido. Fennel fruit contains mainly with essential oils, such as anethole. It also contains lignan and flavonoids that are predicted having an estrogen-like eff ect or as phytoestrogen. Phytoestrogen is weak agonists for estrogen and can elicit statistic signifi cantly increases in uterine wet weight, at definite dose, in the uterothrophic bioassay. It is known that estrogen has eff ect on woman’s sexual organ, such as proliferation of uterine, mammary and ovary. The aim of this research was to investigate the estrogenic eff ect of fennel fruit’s ethanolic extract in immature, 19 days old, Wistar female rats. These models represent the climacteric/menopause phase, where estrogen level is very low because in this age, estrogen not yet produced by ovary. The testing animals were divided into fi ve groups, namely normal group, estradiol control group and three level doses of fennel extract (30 mg/200 g BW; 60 mg/200 g BW and 120 mg/200 g BW). The result indicated that start on 60 mg/200 g BW, fennel extract signifi cantly (α=0.05) increased wet weight of uterine. Fennel extract also lengthen the uterine and increased proliferation of uterine, such as uterine diameters, endometrium diameters and uterine thickness on dose 60mg/200gBW and 120mg/200gBW. Analysis of vaginal smear showed vaginal lubrication eff ect, surprisingly start on 60mg/200BW could induce estrous cycle.


Author(s):  
Safeer Abbas ◽  
Razia Iqbal ◽  
Muhammad Zeeshan Butt ◽  
Sadaf Niaz ◽  
Sumbal Haleem ◽  
...  

The present study was designed to assess the teratogenic effects of Chlorantraniliprole on chick embryos (Gallus gallus domesticus). Different doses of commercial Chlorantraniliprole (0.1, 0.5, 1.0 and 1.5µl/1000µl/egg, in four experimental groups B, C, D, and E respectively) were injected into the yolk sac of eggs before incubation. Embryos were recovered at day 12 of incubation. The mortality rate gradually increased from lower to higher doses. A total of twelve morphometric parameters viz., wet body weight, crown rump length, anterior posterior head diameter, eye diameter, beak length, neck length, humor length, radius and ulna length, metacarpus length, femur length, fibula length and metatarsus length were recorded and compared with control group. These quantitative parameters indicated significant (p>0.05) decreases in all treated groups compared to control group. While the qualitative anomalies such as microcephaly, hydrocephaly, edematous swelling, hematoma formation, abnormal body coloration, microphthalmia, deformed beak, agnathia, micromelia, amelia, omphalocele and ectopia cardis were also observed in treated groups as compared to untreated groups. Therefore it is concluded that Chlorantraniliprole has potentially harmful effects on the development of avian embryos even at very low dose concentration. Hence, due to toxicity of this pesticide it can be used with utmost caution.


Author(s):  
T. M. Crisp ◽  
F.R. Denys

The purpose of this paper is to present observations on the fine structure of rat granulosa cell cultures grown in the presence of an adenohypophyseal explant and to correlate the morphology of these cells with progestin secretion. Twenty-six day old immature female rats were given a single injection of 5 IU pregnant mares serum gonadotropin (PMS) in order to obtain ovaries with large vesicular follicles. At 66 hrs. post-PMS administration (estrus indicated by vaginal smear cytology), the ovaries were removed and placed in a petri dish containing medium 199 and 100 U penicillin/streptomycin (P/S)/ml. Under a 20X magnification dissecting microscope, some 5-8 vesicular follicles/ovary were punctured and the granulosa cells were expressed into the surrounding medium. The cells were transferred to centrifuge tubes and spun down at 1000 rpm for 5 mins.


Author(s):  
I.C. Murray

In women, hyperprolactinemia is often due to a prolactin (PRL)-secreting adenoma or PRL cell hyperplasia. RRL excess stimulates the mammary glands and causes proliferation of the alveolar epithelium. Bromocriptine, a dopamine agonist, inhibits PRL secretion and is given to women to treat nonpuerperal galactorrhea. Old female rats have been reported to have PRL cell hyperplasia or adenoma leading to PRL hypersecretion and breast stimulation. Herein, we describe the effect of bromocriptine and consequently the reduction in serum PRL levels on the ultrastructure of rat mammary glands.Female Long-Evans rats, 23 months of age, were divided into control and bromocriptine-treated groups. The control animals were injected subcutaneously once daily with a 10% ethanol vehicle and were later divided into a normoprolactinemic control group with serum PRL levels under 30 ng/ml and a hyperprolactinemic control group with serum PRL levels above 30 ng/ml.


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