Disruption of deiodinase type 2 in zebrafish disturbs male and female reproduction

Thyroid hormones are crucial mediators of many aspects of vertebrate life, including reproduction. The key player is the biologically active 3,5,3’-triiodothyronine (T3), whose local bio-availability is strictly regulated by deiodinase enzymes. Deiodinase type 2 (Dio2) is present in many tissues and is the main enzyme for local T3 production. To unravel its role in different physiological processes, we generated a mutant zebrafish line, completely lacking Dio2 activity. Here we focus on the reproductive phenotype studied at the level of offspring production, gametogenesis, functioning of the hypothalamic–pituitary–gonadal axis and sex steroid production. Homozygous Dio2-deficient zebrafish were hypothyroid, displayed a delay in sexual maturity and the duration of their reproductive period was substantially shortened. Fecundity and fertilization were also severely reduced. Gamete counts pointed to a delay in oogenesis at onset of sexual maturity and later on to an accumulation of oocytes in mutant ovaries due to inhibition of ovulation. Analysis of spermatogenesis showed a strongly decreased number of spermatogonia A at onset of sexual maturity. Investigation of the hypothalamic–pituitary–gonadal axis revealed that dysregulation was largely confined to the gonads with significant upregulation of igf3, and a strong decrease in sex steroid production concomitant with alterations in gene expression in steroidogenesis/steroid signaling pathways. Rescue of the phenotype by T3 supplementation starting at 4 weeks resulted in normalization of reproductive activity in both sexes. The combined results show that reproductive function in mutants is severely hampered in both sexes, thereby linking the loss of Dio2 activity and the resulting hypothyroidism to reproductive dysfunction.

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17β-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract

Clinical Science ◽

10.1042/cs1010485 ◽

2001 ◽

Vol 101 (5) ◽

pp. 485-491 ◽

Cited By ~ 7

Author(s):

Toshikazu SANO ◽

Gen HIRASAWA ◽

Junji TAKEYAMA ◽

Andrew D. DARNEL ◽

Takashi SUZUKI ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Sex Steroids ◽

Enzyme Assay ◽

Biological Significance ◽

Biologically Active ◽

Sex Steroid ◽

Human Gastrointestinal Tract ◽

Colon And Rectum ◽

Tissue Specimens

The 17β-hydroxysteroid dehydrogenases (17βHSDs) play an important role in the regulation of intracellular levels of biologically active sex steroid hormones in various human tissues. To date, eight distinctive 17βHSD enzymes have been cloned and characterized in humans. Among these isoenzymes, 17βHSD type 2 (17βHSD2) catalyses the conversion of testosterone into androstenedione and/or oestradiol into oestrone in various tissues, and it has thus been suggested to be involved in the biological inactivation of these sex steroids. The human gastrointestinal tract and liver are considered as the principle sites of inactivation and metabolism of various forms of orally administered sex steroids. We therefore examined 17βHSD2 expression and activity in human adult non-pathological gastrointestinal tract in order to clarify further the biological significance of this enzyme. A total of 80 specimens (40 from males and 40 from females) of normal oesophageal, stomach, duodenal, ileal, colonic and rectal tissues were examined for immunohistochemistry. Altogether, 17 tissue specimens were used for enzyme assay, and eight for RNA analysis. 17βHSD2 activity was detected in the stomach, duodenum, ileum, colon and rectum. 17βHSD2 mRNA was most abundant in the small intestine. 17βHSD2 immunoreactivity was localized almost exclusively to the absorptive epithelium, which may be involved in the inactivation of excessive endogenous and exogenous active sex steroids. Results from the present study thus suggest that the human gastrointestinal tract is an important sex steroid metabolizing organ in humans.

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Population dynamics of Sesarma rectum (Crustacea: Brachyura: Grapsidae) in the Ariquindá River mangrove, north-east of Brazil

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315411000130 ◽

2011 ◽

Vol 91 (7) ◽

pp. 1395-1401 ◽

Cited By ~ 4

Author(s):

Daniela da Silva Castiglioni ◽

Paloma Joana Albuquerque de Oliveira ◽

Josivan Soares da Silva ◽

Petrônio Alves Coelho

Keyword(s):

Sex Ratio ◽

Sexual Maturity ◽

Carapace Width ◽

Reproductive Activity ◽

Reproductive Period ◽

Size Class ◽

Adult Males ◽

North East ◽

Class Frequency ◽

Autumn And Winter

This study was carried out in order to provide basic information on the population ecology of the crab Sesarma rectum in the Ariquindá River mangrove, Tamandaré, State of Pernambuco, Brazil. The population was analysed with regard to the following aspects, in particular: the size-class frequency distribution of carapace width (CW), mean body size (CW) of males and females, morphological sexual maturity, sex-ratio, reproductive period, and recruitment. Samples were collected monthly from April 2008 through to March 2009; the crabs were collected manually, with a capture effort by one person for 30 minutes, during low tide. The specimens obtained were measured for CW, length of the propodus of males, and abdomen width of females; and the sex and ovigerous condition were noted. Altogether, we obtained 511 specimens (132 juvenile and 137 adult males, and 171 juvenile and 71 adult females, of which 32 were ovigerous). The median CW of males (16.15 mm) was significantly larger than that of females (13.82 mm) (P < 0.05). The size at morphological sexual maturity was 15.73 mm in males and 16.71 mm in females. The sex-ratio for the total of specimens analysed was 1.11:1 (male:female) (P > 0.05). The sex-ratio by size-class showed an anomalous pattern, with a greater abundance of males in the larger size-classes. The reproductive period was continuous and the highest frequency of ovigerous females was recorded in the spring and summer. The major pulse of recruitment occurred during autumn and winter, which is related to greater reproductive activity during the warmer months of the year.

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New data on the reproductive activity of Mugil cephalus L. from Algerian coast

Zoology and Ecology ◽

10.35513/21658005.2021.2.7 ◽

2021 ◽

pp. 134-147

Author(s):

Racha Boubekeur ◽

Zouhir Ramdane

Keyword(s):

Sexual Maturity ◽

Gonadosomatic Index ◽

Reproductive Activity ◽

Reproductive Period ◽

Mugil Cephalus ◽

Hepatosomatic Index ◽

High Fecundity ◽

Muscle Tissues ◽

Algerian Coast ◽

Reproduction Activity

The aim of this study was to provide additional insight into the reproductive activity of Mugil cephalus L. along the Algerian coast. All specimens were sampled from local commercial fisheries from January 2017 to January 2018. The reproductive period and the size at first sexual maturity were determined. Our results show that the males reach sexual maturity at smaller lengths (28.8 cm) than females (34.5 cm) and that sex ratio is female-skewed (63% vs 37%). The peak of reproductive activity took place from August to October, and spawning took place in November. Sexual rest occurred during subsequent months with a tendency of fattening from December to April. The seasonal evolution of the gonadosomatic index suggests that M. cephalus breeds from August to October. The analysis of the evolution of hepatosomatic index and Fulton’s K apparently reveal no contribution of liver and muscle tissues to the reproduction activity of this species. The high fecundity estimated could be considered a reproductive strategy to maximise the survival of juveniles.

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Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)

Current Hypertension Reviews ◽

10.2174/1573402116999201209203015 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mayank Chaudhary

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Renin Angiotensin System ◽

Blood Pressure Regulation ◽

Biologically Active ◽

Pressure Regulation ◽

Tissue Remodelling ◽

Critical Pathway

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.

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Biologically active Rep proteins of adeno-associated virus type 2 produced as fusion proteins in Escherichia coli.

Journal of Virology ◽

10.1128/jvi.68.2.797-804.1994 ◽

1994 ◽

Vol 68 (2) ◽

pp. 797-804 ◽

Cited By ~ 60

Author(s):

J A Chiorini ◽

M D Weitzman ◽

R A Owens ◽

E Urcelay ◽

B Safer ◽

...

Keyword(s):

Escherichia Coli ◽

Virus Type ◽

Fusion Proteins ◽

Biologically Active ◽

Adeno Associated Virus ◽

Rep Proteins

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Can We Decrease Epicardial and Pericardial Fat in Patients With Diabetes?

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/10742484211006997 ◽

2021 ◽

pp. 107424842110069

Author(s):

Emir M. Muzurović ◽

Snežana Vujošević ◽

Dimitri P. Mikhailidis

Keyword(s):

Myocardial Dysfunction ◽

Biologically Active ◽

Therapeutic Interventions ◽

Cvd Risk ◽

Fat Deposits ◽

Patients With Diabetes ◽

Calorie Diet ◽

Cv Disease ◽

Secretory Pattern

Diabetes mellitus (DM) is a chronic and complex metabolic disorder and also an important cause of cardiovascular (CV) disease (CVD). Patients with type 2 DM (T2DM) and obesity show a greater propensity for visceral fat deposition (and excessive fat deposits elsewhere) and the link between adiposity and CVD risk is greater for visceral than for subcutaneous (SC) adipose tissue (AT). There is growing evidence that epicardial AT (EAT) and pericardial AT (PAT) play a role in the development of DM-related atherosclerosis, atrial fibrillation (AF), myocardial dysfunction, and heart failure (HF). In this review, we will highlight the importance of PAT and EAT in patients with DM. We also consider therapeutic interventions that could have a beneficial effect in terms of reducing the amount of AT and thus CV risk. EAT is biologically active and a likely determinant of CV morbidity and mortality in patients with DM, given its anatomical characteristics and proinflammatory secretory pattern. Consequently, modification of EAT/PAT may become a therapeutic target to reduce the CV burden. In patients with DM, a low calorie diet, exercise, antidiabetics and statins may change the quantity of EAT, PAT or both, alter the secretory pattern of EAT, improve the metabolic profile, and reduce inflammation. However, well-designed studies are needed to clearly define CV benefits and a therapeutic approach to EAT/PAT in patients with DM.

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Programming of the reproductive axis by hormonal and genetic manipulation in mice

Reproduction ◽

10.1530/rep-18-0054 ◽

2018 ◽

Cited By ~ 2

Author(s):

Susana B Rulli ◽

María Julia Cambiasso ◽

Laura D Ratner

Keyword(s):

Sex Chromosome ◽

Genetic Manipulation ◽

Sex Differentiation ◽

Reproductive Function ◽

Gonadal Steroids ◽

Critical Periods ◽

Female Reproduction ◽

Control Male ◽

Male And Female ◽

The Brain

In mammals, the reproductive function is controlled by the hypothalamic-pituitary-gonadal axis. During development, mechanisms mediated by gonadal steroids exert an imprinting at the hypothalamic-pituitary level, by establishing sexual differences in the circuits that control male and female reproduction. In rodents, the testicular production of androgens increases drastically during the fetal/neonatal stage. This process is essential for the masculinization of the reproductive tract, genitals and brain. The conversion of androgens to estrogens in the brain is crucial for the male sexual differentiation and behavior. Conversely, feminization of the brain occurs in the absence of high levels of gonadal steroids during the perinatal period in females. Potential genetic contribution to the differentiation of brain cells through direct effects of genes located on sex chromosomes is also relevant. In this review, we will focus on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal axis of transgenic mice with persistently elevated expression of the human chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal steroids due to a constant hCG stimulation is able to disrupt the developmental programming of the hypothalamic-pituitary axis in both transgenic males and females. Locally produced estrogens by the hypothalamic aromatase might play a key role in the phenotype of these mice. The “four core genotypes” mouse model demonstrated a potential influence of sex chromosome genes in brain masculinization before critical periods of sex differentiation. Thus, hormonal and genetic factors interact to regulate the local production of the neurosteroids necessary for the programming of the male and female reproductive function.

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Subfertility in androgen-insensitive female mice is rescued by transgenic FSH

Reproduction Fertility and Development ◽

10.1071/rd16022 ◽

2017 ◽

Vol 29 (7) ◽

pp. 1426 ◽

Cited By ~ 2

Author(s):

K. A. Walters ◽

M. C. Edwards ◽

M. Jimenez ◽

D. J. Handelsman ◽

C. M. Allan

Keyword(s):

Androgen Receptor ◽

Litter Size ◽

Ovarian Function ◽

Reproductive Function ◽

Antral Follicle ◽

Female Fertility ◽

Wild Type ◽

Female Reproduction ◽

Androgen Insensitivity ◽

Female Mice

Androgens synergise with FSH in female reproduction but the nature of their interaction in ovarian function and fertility is not clear. In the present study, we investigated this interaction, notably whether higher endogenous FSH can overcome defective androgen actions in androgen receptor (AR)-knockout (ARKO) mice. We generated and investigated the reproductive function of mutant mice exhibiting AR resistance with or without expression of human transgenic FSH (Tg-FSH). On the background of inactivated AR signalling, which alone resulted in irregular oestrous cycles and reduced pups per litter, ovulation rates and antral follicle health, Tg-FSH expression restored follicle health, ovulation rates and litter size to wild-type levels. However, Tg-FSH was only able to partially rectify the abnormal oestrous cycles observed in ARKO females. Hence, elevated endogenous FSH rescued the intraovarian defects, and partially rescued the extraovarian defects due to androgen insensitivity. In addition, the observed increase in litter size in Tg-FSH females was not observed in the presence of AR signalling inactivation. In summary, the findings of the present study reveal that FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility.

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Effects of Melatonin on Peripheral Reproductive Function: Regulation of Testicular GnIH and Testosterone

Endocrinology ◽

10.1210/en.2011-1053 ◽

2011 ◽

Vol 152 (9) ◽

pp. 3461-3470 ◽

Cited By ~ 57

Author(s):

Nicolette L. McGuire ◽

Kristina Kangas ◽

George E. Bentley

Keyword(s):

Expression Patterns ◽

Reproductive Function ◽

Melatonin Receptors ◽

Sex Steroid ◽

European Starlings ◽

Steroid Secretion ◽

Local Inhibition ◽

Gonadotropin Inhibitory Hormone ◽

The Brain

Study of seasonal reproduction has focused on the brain. Here, we show that the inhibition of sex steroid secretion can be seasonally mediated at the level of the gonad. We investigate the direct effects of melatonin on sex steroid secretion and gonadal neuropeptide expression in European starlings (Sturnus vulgaris). PCR reveals starling gonads express mRNA for gonadotropin inhibitory hormone (GnIH) and its receptor (GnIHR) and melatonin receptors 1B (Mel 1B) and 1C (Mel 1C). We demonstrate that the gonadal GnIH system is regulated seasonally, possibly via a mechanism involving melatonin. GnIH/ GnIHR expression in the testes is relatively low during breeding compared with outside the breeding season. The expression patterns of Mel 1B and Mel 1C are correlated with this expression, and melatonin up-regulates the expression of GnIH mRNA in starling gonads before breeding. In vitro, GnIH and melatonin significantly decrease testosterone secretion from LH/FSH-stimulated testes before, but not during, breeding. Thus local inhibition of sex steroid secretion appears to be regulated seasonally at the level of the gonad, by a mechanism involving melatonin and the gonadal GnIH system.

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