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Melatonin on hypothyroidism and gonadal development in rats: a review.

ABSTRACT: We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid disorders due to iodine deficiency affect about 740 million people worldwide. Hypothyroidism is a thyroid dysfunction characterized by hypometabolism of the gland, with reduced or physiologically normal T3 and T4 serum levels, and high TSH level. This disorder occurs mainly in adult women in the reproductive phase, with a prevalence of 2% among the world's female population, with profound repercussions on gestation and fetal formation. During the gestational period, the thyroid is initially stimulated by high concentrations of human chorionic gonadotrophin; thus, maintaining maternal euthyroidism during pregnancy and lactation is fundamental for fetal growth and development. Besides, the hormones produced by this gland are involved in the formation of various organs, such as the skin, brain and gonads. Hypothyroidism is associated with several menstrual abnormalities, anovulation and hyperprolactinemia, resulting in a high rate of abortions, premature births, placental rupture, and weight-related neonatal deficits. In addition, there are studies showing that hypothyroidism can affect ovarian morphology (number of ovarian follicles) and testicular morphology (changes in the testicular-lumen epithelium). Melatonin is a hormone known to modulate the estrous cycle and pregnancy, and studies show that the exogenous application of melatonin increased T4 levels in female rats and controlled the decrease in T3 serum levels, reverting the sigs of hypothyroidism.

SUBMITTER: Albuquerque YML

PROVIDER: S-EPMC7558891 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Melatonin on hypothyroidism and gonadal development in rats: a review.

Albuquerque Yuri Mateus Lima de YML Silva Welma Emídio da WED Souza Francisco de Assis Leite FAL Teixeira Valéria Wanderley VW Teixeira Álvaro Aguiar Coelho ÁAC

JBRA assisted reproduction 20201006 4

We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid disorders due to iodine deficiency affect about 740 million people worldwide. Hypothyroidism is a thyroid dysfunction characterized by hypometabolism of the gland, with reduced or physiologically normal T3 and T4 serum levels, and high TSH level. This disorder occurs mainly in adult women in the reproductive phase, with a prevalence of 2 ...[more]

PMID: 32945645

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Project description:The goose industry represents a significant sector within the broader waterfowl industry in China, with early gonadal development playing a pivotal role in enhancing population productivity. Melatonin plays a crucial role in regulating early gonadal development, but the molecular mechanism underlying the effect of melatonin as a regulator remains unclear. In this study, the relationship between melatonin and egg production performance in Jilin white goose was first established, then, an in Ovo injection of melatonin in goose embryos on the embryonic day 12 (E12) was performed to evaluate the impact of melatonin on the gonadal development in Jilin white goose. The results showed that the in Ovo injection of melatonin increased the expression of FOXL2 in the gonads while decreasing the expression of CYP19A1. Transcriptome analyses revealed that a total of 1184 differentially expressed genes were screened in Jilin white goose embryonic gonads among the two comparison groups. These DEGs were enriched in Gene Ontology (GO) terms related to the microtubule cytoskeleton, cytoskeleton, cell adhesion, and biological adhesion and the KEGG enrichment analysis suggested that the DEGs were mainly enriched in "MAPK signaling pathway", "Wnt signaling pathway", "Calcium signaling pathway", "Focal adhesion", "Neuroactive ligand-receptor interaction", "Melanogenesis", "mTOR signaling pathway", "ECM-receptor interaction", and "TGF-beta signaling pathway" in the two comparison groups. The protein-protein interaction network analysis (PPI) indicated that selected DEGs, such as PDIA3, ATCB, PKM, PGAM1, NME2, LDHB, and CALM2, were highly related to the regulation of the reproduction system development. Additionally, the expression trends of 4 identified DEGs were validated by RT-qPCR. In conclusion, this study elucidates the potential regulatory role of melatonin in gonadal development in geese, identifying candidate genes involved in early gonadal differentiation and maturation. Furthermore, the findings offer valuable practical implications for the goose industry, providing professionals with scientifically grounded strategies to enhance reproductive efficiency and overall population productivity.

Project description:A method to mitigate or possibly eliminate reproduction in farmed fish is highly demanded. The existing approaches have certain applicative limitations. So far, no immunization strategies affecting gonadal development in juvenile animals have been developed. We hypothesized that autoimmune mechanisms, occurring spontaneously in a number of diseases, could be induced by targeted immunization. We have asked whether the immunization against specific targets in a juvenile zebrafish gonad will produce an autoimmune response, and, consequently, disturbance in gonadal development. Gonadal soma-derived factor (Gsdf), growth differentiation factor (Gdf9), and lymphocyte antigen 75 (Cd205/Ly75), all essential for early gonad development, were targeted with 5 immunization tests. Zebrafish (n = 329) were injected at 6 weeks post fertilization, a booster injection was applied 15 days later, and fish were sampled at 30 days. We localized transcripts encoding targeted proteins by in situ hybridization, quantified expression of immune-, apoptosis-, and gonad-related genes with quantitative real-time PCR, and performed gonadal histology and whole-mount immunohistochemistry for Bcl2-interacting-killer (Bik) pro-apoptotic protein. The treatments resulted in an autoimmune reaction, gonad developmental retardation, intensive apoptosis, cell atresia, and disturbed transcript production. Testes were remarkably underdeveloped after anti-Gsdf treatments. Anti-Gdf9 treatments promoted apoptosis in testes and abnormal development of ovaries. Anti-Cd205 treatment stimulated a strong immune response in both sexes, resulting in oocyte atresia and strong apoptosis in supporting somatic cells. The effect of immunization was FSH-independent. Furthermore, immunization against germ cell proteins disturbed somatic supporting cell development. This is the first report to demonstrate that targeted autoimmunity can disturb gonadal development in a juvenile fish. It shows a straightforward potential to develop auto-immunization-based technologies to mitigate fish reproduction before they reach maturation. However, the highly variable results between treatments and individuals suggest significant optimization should be performed to achieve the full potential of this technology.

Project description:BackgroundIt is unclear whether the offspring of subclinical hypothyroidism (SCH) pregnant rats still have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect of early L-T4 intervention on the heart development of offspring of SCH pregnant rats and its possible molecular mechanism.MethodsEighty female Wistar rats were randomly divided into Sham group (placebo control), SCH group, LT4-E10 group (L-T4 treatment started on the 10th day of gestation), and LT4-E13 group (L-T4 treatment started on the 13th day of gestation). Each group was further divided into E16 (16th day of gestation), E18 (18th day of gestation), P5 (5th day postnatal day), and P10 (10th day postnatal day) subgroups. The levels of serum TT4 and TSH, the ratio of heart weight to body weight of offspring rats, the expression of metabolic enzymes, and the histopathology of cardiomyocytes were determined. To elucidate the effects of L-T4 on cardiac development of offspring of SCH pregnant rats, the expression levels of GATA4, Nkx2-5 and proteins involved in BMP4/Smad4 signaling pathway were detected by immunohistochemistry, real time quantitative polymerase chain reaction and Western blotting to elucidate the molecular mechanism of L-T4 regulating the heart development of the offspring of SCH pregnant rats.ResultsCompared with Sham group, serum TSH was significantly increased in SCH pregnant rats. Moreover, early L-T4 intervention significantly reduced the levels of serum TSH. Compared with the offspring in the SCH group, early L-T4 intervention significantly increased the heart weight, heart weight to body weight ratio, the activities of succinate dehydrogenase (SDH), Na+/K+-ATPase and Ca2+-ATPase, but reduced myocardial cell shrinkage and nuclear staining, hyperemia/congestion and vacuolar degeneration. In addition, early L-T4 intervention not only significantly increased the mRNA and protein expression of Gata4 and Nkx2-5, but also increased the protein expression involved in BMP4/Smad4 signal pathway in myocardium of the offspring of SCH pregnant rats.ConclusionsEarly L-T4 intervention can regulate the cardiac development of the offspring of SCH pregnant rats by activating BMP4/Smad4 signaling pathway and increasing the expression of Gata4 and Nkx2-5 proteins.

Project description:IntroductionThe reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin's effects on the reproductive system, there is conflicting information regarding melatonin synthesis modulation in hypothyroidism. The objective of this study was to investigate the modulation of plasma melatonin levels and gene expression of Aanat and Asmt in the pineal gland and gonads of rats with hypothyroidism at different times of the day.MethodsFemale and male Wistar rats were divided into control and hypothyroid groups. Hypothyroidism was induced using propylthiouracil (PTU) for 15 days, rats were euthanized six hours after lights on (ZT6), before lights off (ZT11.5), and six hours after lights off (ZT18). Free thyroxine (FT4) and melatonin were quantified in plasma, and gene expressions of melatonin synthesizing enzymes (Aanat and Asmt) were measured in pineal and sexual organs (testis and ovary). Also, morphological analysis was performed in sexual organs.ResultsThe results reveal some disparities between the sexes. Hypothyroidism reduced antral and primary follicles in the ovary, and reduced the weight of testis, epididymis, and prostate. In relation to gene expression, we observed a reduction in Aanat expression in the pineal gland during the light phase (ZT6), and in males, this reduction occurred during the dark phase (ZT18). Regarding Asmt expression, there was a decrease in females also during the dark phase (ZT18). In the gonads, there was an increase in expression in both sexes at ZT11.5. Additionally, it was interesting to observe the association between FT4 levels and Asmt expression in the gonads.ConclusionsThis study showed that acute hypothyroidism can affect components of the melatonergic system in gonads, particularly gene expression of melatonin synthesis enzymes (Aanat and Asmt) contributing to changes in reproduction organs during disease progression. These findings enhance our understanding of melatonin synthesis in the reproductive system during hypothyroidism, showing distinct responses in male and female rats, and suggest that hypothyroidism affects the circadian rhythmicity of melatonin synthesis in a sex-dependent manner.

Project description:ImportancePrevious work demonstrated postoperative hypothyroidism adversely affects wound healing in salvage laryngectomy. Currently, no studies have evaluated the association between wound healing and hypothyroidism in patients undergoing salvage oropharyngectomy.ObjectiveThe primary objective was studying hypothyroidism and other factors associated with oropharyngocutaneous fistula development and fistula requiring reoperation within 30 days after salvage oropharyngectomy.DesignRetrospective cohort study.SettingTertiary academic center.ParticipantsAll patients who underwent salvage oropharyngectomy for recurrent or second primary oropharyngeal squamous cell carcinoma between 2001 and 2017 after radiation or chemoradiation. Patients with no preoperative thyroid-stimulating hormone (TSH) values were excluded.ExposuresSalvage oropharyngectomy for recurrent or second primary oropharyngeal squamous cell carcinoma.Main outcomes measuresThe principle explanatory variable was postoperative hypothyroidism, defined as TSH greater than 5.5 mIU/L. Univariate, bivariate, and binary logistical regression multivariate analysis was performed.ResultsFifty-three patients met inclusion criteria, 37.7% of patients developed hypothyroidism, 18.9% developed a fistula, and 9.4% required an operation to manage the fistula. Postoperative fistula rate was 35% among hypothyroid patients, which was significantly greater than among euthyroid patients (9.1%; P = .03). A fistula requiring reoperation occurred in 20% of hypothyroid patients compared with that of euthyroid patients (3%; P = .061). In a multivariate analysis, postoperative hypothyroid patients were at a 9.5-fold increased risk of developing a fistula [95% confidence interval (CI) 1.6-57.0, P = .013]. Additionally, postoperative hypothyroid patients were at 13.6-fold increased risk for development of a fistula requiring reoperation (95% CI 1.2-160.5, P = .038).Conclusions and relevancePostoperative hypothyroidism in patients who underwent salvage oropharyngectomy can predict fistula development and fistula requiring operative management. This study supports the treatment of hypothyroidism after surgery to reduce wound complications.

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Melatonin on hypothyroidism and gonadal development in rats: a review.

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Melatonin on hypothyroidism and gonadal development in rats: a review.

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