Objective: he aim of the study was to determine the influence of maternal sodium valproate (SVP) on neonatal neuroendocrine (hypothalamic-pituitary-adrenal; HPA)-cytokines and oxido-inflammatory axes. Methods: Pregnant rats (Rattus norvegicus) were orally administered (by gavage) SVP (50 mg/kg) from gestation day (GD) 8 to lactation day (LD) 21. Results: The elevation in serum corticotropin-releasing hormone (CRH), corticosterone, and adrenocorticotropic hormone (ACTH) levels was highly significant at postnatal days (PNDs) 14 and 21 in both dams and neonates of the maternal SVPtreated group relative to those in the control group. However, hypercortisolism (cortisolemia) was highly significant in neonates at both PNDs 14 and 21 while in dams, it was not significantly increased at LD 14 but was at LD 21. This disruption caused adverse effects on maternal food consumption and maternal/neonatal body weight. The maternal SVP treatment resulted in higher levels of neonatal serum adrenaline, noradrenaline, neuropeptide Y (NPY), tumor necrosis factor-alpha (TNF-α), leptin, interleukins (IL-1β, IL-17, IL-4, IL-6 & IL-2), transforming growth factor-beta (TGF-β), and prostaglandin E2 (PGE2), and lower levels of neonatal serum growth hormone (GH), insulin growth factor-1 (IGF-1) and adiponectin at both PNDs. This administration also induced the oxidative stress in neonatal cerebrum and cerebellum at both tested PNDs via the production of free radicals (malondialdehyde; MDA & nitric oxide; NO) and reduction of antioxidant parameters (glutathione; GSH, superoxide dismutase; SOD & catalase; CAT). Conclusion: Maternal SVP treatment stimulated neonatal stress-brain (HPA) axis, resulted in an oxido-inflammatory state, and disrupted the neuroendocrine-cytokines axis, and generally neonatal health.

Thyroid hormones (THs) are involved in the programming of early prenatal period . Moreover, adipokines [leptin (LEP), resistin (RETN), adiponectin (ADP), inflammatory cytokines [interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)], and chemokines ] play an important role during the fetal development and early life [12,32,33]. THs also control the actions of LEP [8,9], interferon-γ [38], ADP [8,9,39], 26], and growth factors [8,28,32,33,35,40,41] by non-genomic mechanisms. Alternatively, LEP, ADP, and TNF-ɑ modulate the functions of thyroid axis and insulin sensitivity [8]. Also, adipokines can regulate the hypothalamic-pituitary-thyroid axis (HPTA), thermogenesis, body weight, basal metabolic rate and appetite [42]. The nuclear receptors such as thyroid receptors (TRs), peroxisome proliferator-activated receptor-α (PPARα), and liver X receptor (LXR) are vital for the triiodothyronine (T3) regulation of cholesterol metabolism and transcription of lipogenic and lipolytic genes [42]. In white adipose tissue (WAT), the expression and secretion of ADP was decreased throughout the pregnancy [13,43]. Moreover, the expression of LEP and RETN was observed in the developing placenta [44] with reducing the insulin level [45]. Also, the coordination in the secretion these cytokines is involved in the availability of energy during the gestation [46].On the other hand, hyperleptinemia was noticed in hypothyroid state [47,48] due to the degradation of leptin [8,14,17,28,49], or stimulation the HPTA in rats [8,14,17,28], canine and human [48,49]. Also, a reduction in the body weight due to the disturbance in the actions of THs, leptin, adiponectin may reflect the decline in the general health during the development [8,17,28,[50][51][52][53]. In hypothyroidism, LEP and ADP caused a dyslipidemia [54], particularly atherogenic dyslipidemia [55]. In parallel, Tsuji et al. [56] stated that there are links between the fetoplacental insufficiency, THs alterations, and immunosuppression. This state might be associated with the cardiovascular dysfunctions [57]. This reduction results from the disruption of the HPTA, the energy expenditure and cytokine networks [8,12,28], and inducing oxidative stress [58], and cell death [59]. Thus, any disorders in the thyroid-adipokines axis might alter the fetoplacental communications. This can inhibit the passage of maternal nutrients to fetuses and delay the critical development. Further additional studies are needed to detect the signaling of this axis during the gestation in human and animals. Conflict of InterestThe author declares that no competing financial interests exist.

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Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

Rapid CommunicationNormal thyroid functions are required during the perinatal development . During the last years, antiepileptic drugs (AEDs) such as sodium valproate (VPA) [40][41][42], phenobarbital(PB) [40], carbamazepine (CBZ) [43], phenytoin (PHT) [40] and lamotrigine (LTG) [41,44] . This may be due to CBZ blocked the voltage-dependent sodium channels [60], and decreased the density [61,62] and permeability of these channels during the early developmental period [63]. These disturbances might be attributed to the imbalance in the maternofetal THs-axis (hypothyroidism) as suggested by Ahmed et al. [29]. This might influence, generally, on the health of the fetuses depending on the degree of the maternofetal hypothyroidism and fetal THbrain dysfunctions.On the other hand, the skeletal anomalies were found in fetuses of rats after the maternal exposure to GBP or VPA (Singh et al., 2014). However, these anomalies were more significant in VPA than GBP. In humans and animals, the teratogenic effects of GBP such as delayed ossifications and skeletal deformations are inconsistent and inconclusive due to the environmental and molecular mechanisms, GBP doses, route and time of administration, animal species and sex type [64][65][66]. Importantly, the fetal skeletal system is more sensitive to GBP during organogenesis in different animal models such as rats [67], mice [68,69] and chick [70]. GBP or VPA can cross the placenta and accumulate in several fetal organs delaying the osteogenesis and chondrogenesis [71][72][73][74][75][76][77]. These variations might be attributed to GBP or VPA can alter the maternofetal mineral and trace elements [78]. In rats, the maternal exposure to 400 mg VPA significantly reduced the level of zinc (Zn, critical for the organogenesis) in both dams and their embryo's [79]. The deficiency in Zn [67,79] and fluctuation in the concentration of GABA (γ-aminobutyric acid) neurotransmitter [66]might be caused skeletal teratogenicity. Thus, Zn may play an important role in the calcification and bone mineralization during the organogenesis [68,69,80]. However, extrapolation of animal investigations to clinics should be importantly scrutinized.On the basis of these data, it can be concluded that the administration of AEDs may cause dysfunctions in the communication between dams and their fetuses, and in the developmental thyroid-brain axis. These effects might depend on the concentration and period of administration of AEDs, and sex type and developmental period of animal species. Additional studies are necessary to clarify the potential associations with human health. Future examinations are needed to explore whether the effect of maternal AEDs on the developmental neuroendocrine system (THs-brain axis) and the cytokines markers play a role in modifying the signaling pathways related to the cellular proliferation and cell death during the perinatal period. Conflict of InterestThe author declares that no competing financial interests exist. Rapid Communication iMedPub Journals