scholarly journals Maternal Vitamin D Deficiency Programs Reproductive Dysfunction in Female Mice Offspring Through Adverse Effects on the Neuroendocrine Axis

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1535-1545 ◽  
Author(s):  
Cari Nicholas ◽  
Joseph Davis ◽  
Thomas Fisher ◽  
Thalia Segal ◽  
Marilena Petti ◽  
...  

Abstract Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function.

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Lucy Pritchard ◽  
Mary Hickson ◽  
Stephen Lewis

AbstractVitamin D (vitD) deficiency is the most common nutritional deficiency worldwide. Most patients are treated with oral vitD capsules (either vitD2 or vitD3). A few studies have reported equal efficacy of buccal spray vitD. This is a new formulation that is absorbed via the oral mucosa into the systemic circulation, bypassing the gastrointestinal route. The main objective of this systematic review was to identify RCT evidence for the comparative effectiveness of buccal spray versus oral vitD on serum 25-hydroxyvitaminD [25-OHD] concentrations and any adverse effects of buccal spray vitD. We have published an a priori protocol using Joanna Briggs Institute (JBI) methodology (PROSPERO CRD42018118580). A three-step search strategy to identify RCTs was conducted, which reported serum 25-OHD concentrations from five databases from 2008–2018. Retrieved abstracts were screened; included papers imported into JBI SUMARI and assessed for study quality (GRADE) by two authors. Meta-analysis was planned. Three RCTs met our inclusion criteria. Due to heterogeneity of studies, meta-analysis was not possible. In a RCT crossover study, mean serum 25-OHD concentrations were significantly higher in patients with malabsorption syndrome (n = 20) on 1000IU buccal spray + 117.8%(10.46, 95%CI6.89,14.03ng/ml) vs.1000IU oral vitD3 + 36.02%(3.96, 95%CI2.37, 5.56ng/ml) at 30days (p < 0.0001). Mean serum 25-OHD were also significantly higher in healthy adults (n = 20) on buccal spray + 42.99%(7.995, 95%CI6.86,9.13ng/ml)vs.oral vitD3 + 21.72%(4.06, 95%CI3.41,4.71ng/ml) at 30days (p < 0.0001). In another RCT crossover study, ANCOVA revealed no significant difference in the mean and SD change from baseline total 25-OHD concentrations in adults (n = 22) on 3000IU buccal spray vs. 3000IU oral vitD3 + 44%,26.15 (SD17.85) vs. + 51%,30.38 (SD17.91)nmol/l, respectively;F = 1.044, adjusted r20.493,p = 0.313 at 4 weeks. In a RCT, 800IU buccal spray was equally effective as 750IU oral vitD3 in children with neurodisabilities(n = 24) at 3 months. Both groups had a significant increase in 25-OHD; 11.5 ng/ml(median8–19) to 26.5(13.6–39)ng/ml and 15.5ng/ml(8–20) to 34.5(22–49)ng/ml, respectively (z = 150;p < 0.0001). The overall certainty of evidence was very low to moderate. No adverse effects were reported. The evidence from these studies suggests that 800IU-3000IU doses of buccal spray vitD3 given daily may be an effective alternative as oral vitD3 in obtaining short-term haematological responses in serum 25-OHD concentrations. Buccal spray vitD3 may be a useful alternative for patients with intestinal malabsorption or dysphagia. Future research should compare buccal spray VD3 to intramuscular injections and confirm these findings in well-designed trials.


2017 ◽  
Vol 312 (4) ◽  
pp. R485-R491 ◽  
Author(s):  
Elizabeth F. Sutton ◽  
Heinrich E. Lob ◽  
Jiunn Song ◽  
YunWei Xia ◽  
Scott Butler ◽  
...  

Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes.


2017 ◽  
Vol 9 (2) ◽  
pp. 208-214 ◽  
Author(s):  
P. Nuñez ◽  
T. Fernandez ◽  
M. García-Arévalo ◽  
P. Alonso-Magdalena ◽  
A. Nadal ◽  
...  

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9–16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.


2019 ◽  
Vol 35 (4) ◽  
pp. 314-323 ◽  
Author(s):  
Toyohito Tanaka ◽  
Toshinari Suzuki ◽  
Akiko Inomata

Previous studies reported that piperonyl butoxide (PBO) induces adverse effects on exploratory behaviour in male mice. However, no consistent effects of PBO treatment were observed in female mice. This study aimed to evaluate PBO’s neurobehavioral effects in female mice. Female mice were exposed to PBO through diet to provide levels of 0 (control), 0.025%, 0.1%, and 0.4% from 5 to 12 weeks of age, and selected behavioural parameters were measured. The average female body weight showed no significant effect from PBO treatment through the experimental periods. Regarding multiple-T water maze performance at 10 weeks of age, no significant effect caused by PBO treatment was observed. Exploratory behaviour examination of 8-week-old female mice indicated that the average speed declined in a significant dose-related manner, and the longitudinal pattern indicated a significant difference between the control and high-dose groups. For exploratory behaviour examination at 11 weeks of age, the total exploration distance shortened in a significant dose-related manner, and the average speed declined similarly. These longitudinal patterns showed significant differences between the control and high-dose groups. The PBO dose levels in this study produced several adverse effects on exploratory behaviour in female mice.


2021 ◽  
Author(s):  
Eva Guilloteau ◽  
Patrice COLL ◽  
Zhuyi LU ◽  
Madjid DJOUINA ◽  
Mathieu CAZAUNAU ◽  
...  

Abstract Background Emerging data indicate that prenatal exposure to air pollution may lead to higher susceptibility to several non-communicable diseases. Limited research has been conducted due to difficulties in modelling realistic air pollution exposure. In this study, pregnant mice were exposed from gestational day 10 to 17 to an atmosphere representative of a 2013 pollution event in Beijing, China. Intestinal homeostasis and microbiota were assessed in both male and female offspring during the suckling-to-weaning transition. Results Sex-specific differences were observed in progeny of gestationally-exposed mice. In utero exposed males exhibited decreased villus and crypt length, vacuolation abnormalities, and lower levels of tight junction protein ZO-1 in ileum. They showed an upregulation of absorptive cell markers and a downregulation of neonatal markers in colon. Cecum of in utero exposed male mice also presented a deeply unbalanced inflammatory pattern. By contrast, in utero exposed female mice displayed less severe intestinal alterations, but included dysregulated expression of Lgr5 in colon, Tjp1 in cecum, and Epcam, Car2 and Sis in ileum. Moreover, exposed female mice showed dysbiosis characterized by a decreased weighted UniFrac β-diversity index, a higher abundance of Bacteroidales and Coriobacteriales orders, and a reduced Firmicutes/Bacteroidetes ratio. Conclusion Prenatal realistic modelling of an urban air pollution event induced sex-specific precocious alterations of structural and immune intestinal development in mice.


Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route


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