Effect of paracetamol treatment on maternal care and reproductive outcomes in female rat offspring

2020 ◽  
Vol 32 (18) ◽  
pp. 1311
Author(s):  
Jeberson F. Aleixo ◽  
Marina R. F. Pereira ◽  
Bruno G. Montagnini ◽  
Matheus Junior D. Pereira ◽  
Simone Forcato ◽  
...  
Keyword(s):  
Sexual Development ◽  
Maternal Care ◽  
Wistar Rats ◽  
Reproductive Behaviour ◽  
Female Offspring ◽  
Female Rat ◽  
Anogenital Distance ◽  
Rat Offspring ◽  
Grooming Behaviour ◽  
Plasma Oestradiol

Paracetamol (PAR) is one of the most commonly used drugs by pregnant women because it is considered safe for the mother and fetus. However, PAR is transferred into breast milk and crosses the blood–placental barrier, being present in the progeny during important stages of development. Intrauterine exposure to PAR may decrease the anogenital distance and follicle reserve in female rodent offspring. Therefore, the aim of the present study was to evaluate whether maternal PAR treatment altered the reproductive behaviour of dams and the sexual development of female rat offspring. Pregnant Wistar rats were gavaged daily with 350mg kg−1 day−1 PAR or water during gestation (from Gestation Day (GD) 6 until delivery) or during gestation and lactation (from GD6 until weaning). Maternal PAR treatment had maternal effects (increased grooming behaviour), and resulted in impaired sexual behaviour, decreased follicle reserve and increased plasma oestradiol concentrations in female offspring.

scholarly journals Reproductive physiology, and physical and sexual development of female offspring born to diabetic dams

2012 ◽  
Vol 56 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Raquel Spadotto ◽  
Débora Cristina Damasceno ◽  
Antonio Francisco Godinho ◽  
Elaine Manoela Porto Amorim ◽  
Juliana Elaine Perobelli ◽  
...  
Keyword(s):  
Sexual Development ◽  
Maternal Diabetes ◽  
Female Offspring ◽  
Physical Development ◽  
Reproductive Physiology ◽  
Female Rats ◽  
Histological Evaluation ◽  
Control Group ◽  
Female Rat ◽  
Rat Offspring

OBJECTIVES: The objective of this study was to evaluate physical and sexual development and reproductive physiology in female rat offspring that developed in hyperglycemia conditions in utero and during lactation. MATERIALS AND METHODS: Maternal diabetes was induced in female rats by a single IV injection of streptozotocin before mating. Female offspring development was evaluated by means of the following parameters: physical development; age of vaginal opening and first estrus; weight and histological evaluation of uterus and ovaries; duration of the estrous cycle, sexual behavior, and fertility after natural mating. RESULTS: In the female offspring, maternal diabetes caused delays in initial physical development; diminution in ovary weight and number of follicles; and inferior reproductive performance compared with the control group. CONCLUSIONS: The exposure to hyperglycemia in uterus and during lactation caused delays in physical and sexual development, and affected the reproductive physiology of female rats negatively.

Maternal quercetin intake during lactation attenuates renal inflammation and modulates autophagy flux in high-fructose-diet-fed female rat offspring exposed to maternal malnutrition

2019 ◽  
Vol 10 (8) ◽  
pp. 5018-5031 ◽  
Author(s):  
Shin Sato ◽  
Toshio Norikura ◽  
Yuuka Mukai
Keyword(s):  
Female Offspring ◽  
Female Rat ◽  
Autophagy Flux ◽  
Maternal Malnutrition ◽  
High Fructose Diet ◽  
Rat Offspring ◽  
Low Protein ◽  
High Fructose ◽  
Protein Diets

Quercetin intake during lactation causes long-term alterations in inflammation and autophagy flux in the kidneys of high-fructose-diet-fed adult female offspring exposed to maternal normal- or low-protein diets.

Prenatal Dexamethasone Exposure Induced Alterations in Neurobehavior and Hippocampal Glutamatergic System Balance in Female Rat Offspring

2019 ◽  
Vol 171 (2) ◽  
pp. 369-384 ◽  
Author(s):  
Songqiang Huang ◽  
Wanting Dong ◽  
Zhexiao Jiao ◽  
Jie Liu ◽  
Ke Li ◽  
...  
Keyword(s):  
Glucocorticoid Receptors ◽  
Female Offspring ◽  
Abnormal Behavior ◽  
Control Group ◽  
Female Rat ◽  
Glutamatergic System ◽  
Fetal Origins ◽  
Histone Deacetylase 2 ◽  
Rat Offspring

Abstract Epidemiological investigations have suggested that periodic use of dexamethasone during pregnancy is a risk factor for abnormal behavior in offspring, but the potential mechanism remains unclear. In this study, we investigated the changes in the glutamatergic system and neurobehavior in female offspring with prenatal dexamethasone exposure (PDE) to explore intrauterine programing mechanisms. Compared with the control group, rat offspring with PDE exhibited spatial memory deficits and anxiety-like behavior. The expression of hippocampal glucocorticoid receptors (GR) and histone deacetylase 2 (HDAC2) increased, whereas histone H3 lysine 14 acetylation (H3K14ac) of brain-derived neurotrophic factor (BDNF) exon IV (BDNF IV) and expression of BDNF decreased. The glutamatergic system also changed. We further observed that changes in the fetal hippocampus were consistent with those in adult offspring. In vitro, the administration of 0.5 μM dexamethasone to the H19-7 fetal hippocampal neuron cells directly led to a cascade of changes in the GR/HDAC2/BDNF pathway, whereas the GR antagonist RU486 and the HDAC2 inhibitor romidepsin (Rom) reversed changes caused by dexamethasone to the H3K14ac level of BDNF IV and to the expression of BDNF. The increase in HDAC2 can be reversed by RU486, and the changes in the glutamatergic system can be partially reversed after supplementation with BDNF. It is suggested that PDE increases the expression of HDAC2 by activating GR, reducing the H3K14ac level of BDNF IV, inducing alterations in neurobehavior and hippocampal glutamatergic system balance. The findings suggest that BDNF supplementation and glutamatergic system improvement are potential therapeutic targets for the fetal origins of abnormal neurobehavior.

Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring

1995 ◽  
Vol 132 (6) ◽  
pp. 765-770 ◽  
Author(s):  
B Díaz López ◽  
MD Colmenero Urquijo ◽  
ME Díaz Rodriguez ◽  
A Arce Fraguas ◽  
A Esquifino Parras ◽  
...  
Keyword(s):  
Sexual Development ◽  
Female Offspring ◽  
The Other ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Prolactin ◽  
Melatonin Treatment ◽  
Control Male ◽  
Rat Offspring ◽  
Old Rats

Díaz López B, Colmenero Urquijo MD, Díaz Rodriguez ME, Arce Fraguas A, Esquifino Parras A, Marín Fernández B, Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring. Eur J Endocrinol 1995;132:765–70. ISSN 0804–4643 Sexual development of female and male rat offspring of control, pinealectomized (PIN-X) or melatonin (MEL 2 50 μg/100 g body wt)-treated mother rats during pregnancy was studied. Newborns were studied at the following phases of sexual development: neonate (5 days old), infantile (15 days old), juvenile (25 and 30 days old) and pubertal phase (55 days). In female offspring, MEL treatment during pregnancy significantly increased plasma luteinizing hormone (LH) in 15- and 25-day-old rats; however, at the end of the prepubertal period (30 days) the concentration of plasma LH decreased significantly as compared to control rats. This hormonal pattern was different from that observed in offspring of control and PIN-X rats, which had low LH levels at 25 days of age and higher LH levels at 30 days of age. Follicle-stimulating hormone (FSH) did not vary significantly among the three groups. Plasma prolactin levels were affected by PIN-X of the mother, showing significantly higher levels in the 5-day-old offspring than in the controls; plasma prolactin levels were also affected by MEL treatment of the mother, producing hyperprolactinemia in the 30-day-old female offspring. In male offspring, sexual development in control male rats progressed rapidly with significantly increased LH and FSH levels at 25 and 30 days compared to those measured during the neonatal and infantile periods. Pinealectomy of the mother induced the following modifications: in 5-, 15- and 30-day-old male rats, decreased LH levels were measured relative to the other two groups studied in 5- and 25-day-old rats, significantly lower FSH levels than in the control rats were recorded. However, in 5- and 15-day-old rats, significantly higher prolactin levels than in control rats were measured. Melatonin injections during pregnancy decreased FSH levels at 5, 25, 30 and 55 days as compared to the control males. Also, MEL increased LH levels in 25-day-old rats and significantly decreased prolactin levels in 15- and 55-day-old rats as compared to the other two groups. These results indicate that the mother's pineal gland and MEL treatment can act on fetal development and influence the postnatal ontogeny of the hormones involved in the neuroendocrine–reproductive axis in developing rats. The effect of MEL was apparent during pubertal stages of the offspring, while the effect of PIN-X was more apparent during the juvenile period of the young rats. Beatriz Díaz López, Dpt. Biología Funcional, Arca Fisiología, Fac, Medicina, Universidad de Oviedo, 33006-Oviedo, Spain

Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure

2007 ◽  
Vol 292 (5) ◽  
pp. R1926-R1933 ◽  
Author(s):  
Xing-Hai Yao ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Adult Female ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Female Offspring ◽  
Female Rat ◽  
Glucose Transporter 4 ◽  
Insulin Resistant ◽  
Rat Offspring

Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g·kg−1·day−1 by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCζ. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCζ in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKCζ phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.

Maternal viral mimetic administration at the beginning of fetal hypothalamic nuclei development accelerates puberty in female rat offspring

2018 ◽  
Vol 96 (5) ◽  
pp. 506-514 ◽  
Author(s):  
Pinar Cakan ◽  
Sedat Yildiz ◽  
Tuba Ozgocer ◽  
Azibe Yildiz ◽  
Nigar Vardi
Keyword(s):  
Viral Infection ◽  
Body Mass ◽  
Time Window ◽  
Critical Time ◽  
Female Offspring ◽  
Poly I:C ◽  
Female Rat ◽  
Pregnant Rats ◽  
Rat Offspring ◽  
Polycytidylic Acid

This study aimed to investigate the effects of maternal viral infection during a critical time window of fetal hypothalamic development on timing of puberty in the female offspring. For that purpose, a viral mimetic (i.e., synthetic double-strand RNA, namely, polyinosinic–polycytidylic acid, poly (I:C)) or saline was injected (i.p.) to the pregnant rats during the beginning (day 12 of pregnancy, n = 5 for each group) or at the end of this time window (day 14 of pregnancy, n = 5 for each group). Four study groups were formed from the female pups (n = 9–10 pups/group). Following weaning of pups, vaginal opening and vaginal smearing was studied daily until 2 sequential estrous cycles were observed. During the second diestrus phase, blood samples were taken for progesterone, leptin, corticosterone, follicle-stimulating hormone, and luteinizing hormone. Maternal poly (I:C) injection on day 12 of pregnancy increased body mass and reduced the time to puberty in the female offspring. Neither poly (I:C) nor timing of injection affected other parameters studied (p > 0.05). It has been shown for the first time that maternal viral infection during the beginning of fetal hypothalamic development might hasten puberty by increasing body mass in rat offspring.

scholarly journals Dopamine Genotype Interacts with Inter-Individual Licking Received on Later-Life Licking Provisioning in Female Rat Offspring

2019 ◽  
Author(s):  
Samantha C. Lauby ◽  
David G. Ashbrook ◽  
Hannan R. Malik ◽  
Diptendu Chatterjee ◽  
Pauline Pan ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Maternal Care ◽  
Early Life ◽  
Later Life ◽  
Human Populations ◽  
Female Rat ◽  
Systematic Analysis ◽  
Dopaminergic Activity ◽  
Rat Offspring ◽  
The Relationship

AbstractIn most mammals, mothers exhibit natural variations in care that propagate between generations of female offspring. However, there is limited information on genetic variation that influences this propagation. We assessed early-life maternal care received by individual female rat offspring in relation to genetic polymorphisms linked to dopaminergic activity, maternal care provisioning, and dopaminergic activity in the maternal brain. We also conducted a systematic analysis of other genetic variants potentially related to maternal behavior in our Long-Evans rat population. We found that dopamine receptor 2 (rs107017253) variation interacted with the relationship between early-life maternal care received and dopamine levels in the nucleus accumbens which, in turn, were associated with later-life maternal care provisioning. We also discovered and validated new variants that were predicted by our systematic analysis. Our findings suggest that genetic variation influences the relationship between maternal care received and maternal care provisioning, similar to findings in human populations.

Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

2019 ◽  
Vol 31 (9) ◽  
Author(s):  
Samantha C. Lauby ◽  
Diptendu Chatterjee ◽  
Pauline Pan ◽  
Patrick O. McGowan ◽  
Alison S. Fleming
Keyword(s):  
Maternal Care ◽  
Female Rat ◽  
Rat Offspring

scholarly journals Protein restriction during pregnancy induces hypertension in adult female rat offspring – influence of oestradiol

2011 ◽  
Vol 107 (5) ◽  
pp. 665-673 ◽  
Author(s):  
K. Sathishkumar ◽  
Rebekah Elkins ◽  
Uma Yallampalli ◽  
Chandra Yallampalli
Keyword(s):  
Adult Female ◽  
Female Offspring ◽  
Protein Restriction ◽  
Intact Protein ◽  
Female Rat ◽  
Pregnant Rats ◽  
Testosterone Levels ◽  
Induced Hypertension ◽  
Plasma Oestradiol

We previously reported that gestational dietary protein restriction in rats causes sex-related differences in development of blood pressure (BP) in the offspring, which is more pronounced in males than in females. As such effects may depend on sex hormones, we investigated the role of oestradiol in the development of hypertension in female offspring of protein-restricted dams. Female offspring of pregnant rats fed normal (20 %) or protein-restricted (6 %) casein diets throughout pregnancy were kept either intact, ovariectomised or ovariectomised with oestradiol supplementation. BP, Plasma oestradiol and testosterone levels, and vascular oestrogen receptor (ER) were examined. BP was significantly higher and plasma oestradiol levels were significantly lower ( − 34 %) in intact protein-restricted female offspring compared to corresponding controls. Further decrease in oestradiol levels by ovariectomy exacerbated hypertension in the protein-restricted females, with an earlier onset and more prominent elevation in BP compared to controls. Oestradiol supplementation in ovariectomised protein-restricted females significantly reversed ovariectomy-induced hypertension but did not normalise BP to control levels. The hypertensive protein-restricted females have reduced vascular ERα expression that was unaffected by ovariectomy or oestradiol replacement. In addition, testosterone levels were significantly higher by 2·4-, 3·4- and 2·8-fold in intact, ovariectomised and oestradiol-replaced protein-restricted females compared to corresponding controls. The present data show that: (1) hypertension in protein-restricted adult female offspring is associated with reduced plasma oestradiol levels; (2) oestradiol protects and limits the severity of hypertension in protein-restricted females and contributes to sexual dimorphism; (3) oestradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ERα receptors and/or increased circulating testosterone levels.

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