Effects of hyperthyroidism and diabetes mellitus on spermatogenesis in peri- and post-pubertal mice

IntroductionDiabetes and thyroid dysfunction often co-exist. One autoimmune disorder always invites another and it has been reported that such co-morbid ailments always become detrimental to the health of the patients.Materials and methodsIn our previous work, we elucidated the interactions of diabetes and hypothyroidism on testicular development and spermatogenesis. However, the present study illuminates the interface between diabetes and hyperthyroidism, where 16 ICR pregnant primiparous mice were used and subsequently 48 male pups were randomly selected (n=12/group) and separated into 4 groups: control (C), diabetic (D), diabetic + hyperthyroidism (DH) and hyperthyroidism (H).ResultsComputerized sperm analyses showed significant reductions in count by 20% and increases of 15% in D and H animals, respectively, vs. controls. However, rapid progressive sperm motility was significantly lower only in D (30%) compared with C mice. Our histomorphometric investigation depicted damaging effects on testicular and epididymal tissues; the stroma adjacent to the seminiferous tubules of the D mice revealed edematous fluid and unstructured material. However, in the epididymis, germ cell diminution contraction of tubules, compacted principal and clear cells, lipid vacuolization, atypical cellular connections, exfoliated epithelial cells, and round spermatids were conspicuous in DH mice.DiscussionCollectively, our experiment was undertaken to ultimately better recognize male reproductive disorders in diabetic-hyperthyroid patients

Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats

It is assumed that nitric oxide synthase and nitric oxide are involved in the regulation of female reproduction. This study aimed to assess the roles of nitric oxide synthase (NOS) in follicular development. The endothelial NOS (eNOS) inhibitor L-NAME, inducible NOS (iNOS) inhibitor S-Methylisothiourea (SMT) and NOS substrate L-arginine (L-Arg) were used in the NOS inhibition models in vivo. Neonatal female rats were treated with phosphate buffer saline (PBS, control), L-NAME (L-NG-Nitroarginine Methyl Ester, 40 mg/kg), SMT (S-Methylisothiourea, 10 mg/kg), L-NAME + SMT, or L-Arg (L-arginine, 50 mg/kg) via subcutaneous (SC) injection on a daily basis for 19 consecutive days, with the samples being collected on specific postnatal days (PD5, PD10, and PD19). The results indicated that the number of antral follicles, the activity of total-NOS, iNOS, neuronal NOS (nNOS), and eNOS, and the content of NO in the ovary were significantly (p < 0.05) increased in the L-Arg group at PD19, while those in L + S group were significantly (p < 0.05) decreased. Meanwhile, the ovarian expression in the L-Arg group in terms of p-AKT, p-FoxO3a, and LC3-II on PD19 were significantly (p < 0.05) upregulated, while the expressions of PTEN and cleaved Caspase-3 were (p < 0.05) downregulated as a result of NOS/NO generation, respectively. Therefore, the results suggest that NOS is possibly involved in the maturation of follicular development to puberty via the PI3K/AKT/FoxO3a pathway, through follicular autophagia and apoptosis mechanisms

The Engrailed-1 Gene Stimulates Brown Adipogenesis

As a thermogenic organ, brown adipose tissue (BAT) has received a great attention in treating obesity and related diseases. It has been reported that brown adipocyte was derived from engrailed-1 (EN1) positive central dermomyotome. However, functions of EN1 in brown adipogenesis are largely unknown. Here we demonstrated that EN1 overexpression increased while EN1 knockdown decreased lipid accumulation and the expressions of key adipogenic genes including PPARγ2 and C/EBPα and mitochondrial OXPHOS as well as BAT specific marker UCP1. Taken together, our findings clearly indicate that EN1 is a positive regulator of brown adipogenesis

Journal of Semiconductors

Abstract: A continuous-time 7th-order Butterworth Gm-C low pass filter (LPF) with on-chip automatic tuning circuit has been implemented for a direct conversion DBS tuner in 0.35 µm SiGe BiCMOS technology. The filter's −3 dB cutoff frequency f 0 can be tuned from 4 to 40 MHz. A novel on-chip automatic tuning scheme has been successfully realized to tune and lock the filter's cutoff frequency. Measurement results show that the filter has −0.5 dB passband gain, +/-5% bandwidth accuracy, 30 nV/Hz 1/2 input referred noise, −3 dBVrms passband IIP3, and 27 dBVrms stopband IIP3. The I/Q LPFs with the tuning circuit draw 13 mA (with f 0 = 20 MHz) from 5 V supply, and occupy 0.5 mm 2

Role of phosphodiesterase in cyclic AMP signaling in cultured rat granulosa cells

Inactivation of the cyclic nucleotide signal in granulosa cells depends on a complex array of cyclic nucleotide phosphodiesterases (PDE). In order to examine the role of PDE in cyclic AMP (cAMP) signaling in granulosa cells, the present study examined the expression of PDE4D proteins and regulation of cAMP-PDE activities in cultured rat granulosa cells. The results of immunoblot analyses showed that two predominant PDE4D subtypes of approximately 80 and 70 kDa appeared when immature rat granulosa cells were treated with FSH. However, these two new subtypes presumed to be PDE4D proteins were not influenced by treatments of DETA/NO, cGMP and PKB inhibitor, LY294002. Immature rat granulosa cells treated with medium alone displayed low cAMP-PDE activity throughout 48 h of culture while those treated with FSH (2 ng·mL–1) showed a marked increase in cAMP-PDE activity between 6 and 12 h of culture, followed by a decline. The findings from the present study indicate that the increased cAMP-PDE activity by FSH is mainly related to the changes of PDE4D protein levels. However, the inhibitory effects of NO on cAMP accumulation in rat granulosa cells are not via the increased cAMP-PDE activity

Denatonium Benzoate-Induces Oxidative Stress in the Heart and Kidney of Chinese Fast Yellow Chickens by Regulating Apoptosis, Autophagy, Antioxidative Activities and Bitter Taste Receptor Gene Expressions

The sense of taste which tells us which prospective foods are nutritious, poisonous and harmful is essential for the life of the organisms. Denatonium benzoate (DB) is a bitter taste agonist known for its activation of bitter taste receptors in different cells. The aim of the current study was to investigate the mRNA expressions of bitter taste, downstream signaling effectors, apoptosis-, autophagy- and antioxidant-related genes and effector signaling pathways in the heart/kidney of chickens after DB dietary exposure. We randomly assigned 240, 1-day-old Chinese Fast Yellow chicks into four groups with five replicates of 12 chicks and studied them for 28 consecutive days. The dietary treatments consisted of basal diet and feed containing DB (5, 20 and 100 mg/kg). The results revealed that dietary DB impaired (p < 0.05) the growth performance of the chickens. Haemotoxylin and eosin staining and TUNEL assays confirmed that medium and high doses of DB damaged the epithelial cells of heart/kidney and induced apoptosis and autophagy. Remarkably, the results of RT-PCR and qRT-PCR indicated that different doses of DB gradually increased (p < 0.05) mRNA expressions of bitter taste, signaling effectors, apoptosis-, autophagy- and antioxidant- related genes on day 7 in a dose-response manner, while, these expressions were decreased (p < 0.05) subsequently by day-28 but exceptional higher (P < 0.05) expressions were observed in the high-dose DB groups of chickens. In conclusion, DB exerts adverse effects on the heart/kidney of chickens in a dose-response manner via damaging the epithelium of the heart/kidney by inducing apoptosis, autophagy associated with bitter taste and effector gene expressions. Correlation analyses for apoptosis/autophagy showed agonistic relationships. Our data provide a novel perspective for understanding the interaction of bitter taste, apoptosis, autophagy and antioxidative genes with bitter taste strong activators in the heart/kidney of chicken. These insights might help the feed industries and pave the way toward innovative directions in chicken husbandry

Smooth muscle cell-specific TMEM16A deletion does not alter Ca2+ signaling, uterine contraction, gestation length or litter size in micedagger

Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance and parturition; thus identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl- channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found that myometrial cells from TMEM16ASMKO mice generated the same pattern and magnitude in Ca2+ signals upon stimulation with KCl, oxytocin and PGF2alpha compared to the isogenic control myometrial cells. At the uterine tissue level, TMEM16A deletion also did not cause detectable changes in either spontaneous or agonist (i.e. KCl, oxytocin and PGF2alpha)-induced contractions. Moreover, in vivo the TMEM16ASMKO mice gave birth at full term with the same litter size as genetically identical control mice. Finally, TMEM16A immunostaining in both control and TMEM16ASMKO mice revealed that this protein was highly expressed in the endometrial stroma, but did not co-localize with a smooth muscle specific marker MYH11. Collectively, these results unequivocally demonstrate that TMEM16A does not serve as a pacemaking channel for spontaneous uterine contraction, neither does it function as a depolarizing channel for agonist-evoked uterine contraction. Yet these two functions could underlie the normal gestation length and litter size in the TMEM16ASMKO mice

A widely tunable continuous-time LPF for a direct conversion DBS tuner

A continuous-time 7th-order Butterworth Gm-C low pass filter (LPF) with on-chip automatic tuning circuit has been implemented for a direct conversion DBS tuner in 0.35μm SiGe BiCMOS technology. The filter's -3 dB cutoff frequency f0 can be tuned from 4 to 40 MHz. A novel on-chip automatic tuning scheme has been successfully realized to tune and lock the filter's cutoff frequency. Measurement results show that the filter has -0.5 dB passband gain, +/- 5% bandwidth accuracy, 30 nV/Hz~(1/2) input referred noise, -3 dBVrms passband IIP3, and 27 dBVrms stopband IIP3. The I/Q LPFs with the tuning circuit draw 13 mA (with f_0 = 20 MHz) from 5 V supply, and occupy 0.5 mm~2

An asymmetric MOSFET-C band-pass filter with on-chip charge pump auto-tuning

An asymmetric MOSFET-C band-pass filter(BPF)with on chip charge pump auto-tuning is presented.It is implemented in UMC (United Manufacturing Corporation)0.18μm CMOS process technology. The filter system with auto-tuning uses a master-slave technique for continuous tuning in which the charge pump OUtputs 2.663 V, much higher than the power supply voltage, to improve the linearity of the filter. The main filter with third order low-pass and second order high-pass properties is an asymmetric band-pass filter with bandwidth of 2.730-5.340 MHz. The in-band third order harmonic input intercept point(HP3) is 16.621 dBm,wim 50 Ω as the source impedance. The input referred noise iS about 47.455μVrms. The main filter dissipates 3.528 mW while the auto-tuning system dissipates 2.412 mW from a 1.8 V power supply. The filter with the auto-tuning system occupies 0.592 mm~2 and it can be utilized in GPS (global positioning system)and Bluetooth systems