Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms

Zu-bin, HE; Yin, Guochao; Li, Qingdi Quentin; Zeng, Qiongfang; Duan, Jinliang

doi:10.21873/invivo.12531

Cited by 36 publications

(21 citation statements)

References 30 publications

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“…Overall, experimental, and epidemiological evidence suggests that PBDEs may mimic and exacerbate the effects of high fat or high-calorie diet as they stimulate lipid accumulation in the liver, decreased glucose tolerance, and insulin sensitivity. These symptoms resemble diabetic and obesity phenotypes, both contributing to male infertility via multiple mechanisms [102][103][104][105]. Discussion of these mechanisms is beyond the scope of the current review.…”

Section: Metabolic Disruptionmentioning

confidence: 97%

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Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

Arowolo¹,

Pilsner²,

Sergeyev³

et al. 2022

Preprint

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Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

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Section: Metabolic Disruptionmentioning

confidence: 97%

“…Discussion of these mechanisms is beyond the scope of the current review. It is important to mention, however, that metabolic disruption associated with obesity and/or diabetes results in a negative impact on semen parameters, including sperm concentration, motility, viability, and normal morphology [102][103][104][105].…”

Section: Metabolic Disruptionmentioning

confidence: 99%

Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

Arowolo¹,

Pilsner²,

Sergeyev³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The biochemical mechanism underlying the changes in male reproductive capacity caused by DM has been the subject of several clinical and animal research. Endocrine problems, neuropathy, elevated oxidative stress and increased level of advanced glycation end products (AGE) are among them ( 11 , 12 ). As the studies show, diabetes causes considerable oxidative stress in females, which leads to DNA damage.…”

Section: Introductionmentioning

confidence: 99%

A systematic review on the role of melatonin and its mechanisms on diabetes-related reproductive impairment in non-clinical studies

Armandeh

Bameri²,

Haghi‐Aminjan³

et al. 2022

Front. Endocrinol.

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BackgroundDiabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin’s effect on the reproductive system adversely affected by diabetes mellitus (DM).MethodsA comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria.ResultsThe results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis.ConclusionMelatonin exerted a protective action on the impaired reproductive system in in-vivo and in-vitro models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.

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“…The latter results from impaired secretion of trophic hormones for the testes and is characterized by low testosterone coupled with abnormally low LH and FSH levels 16 . The recent studies have attempted to clarify the metabolic‐related testosterone decline in diabetes due to whether testicular, hypothalamus or pituitary defects 15,25 . Hypogonadotropic hypogonadism (HH) is the major form of secondary hypogonadism and previous documents suggested that HH occurs commonly in young and middle‐aged male type 2 diabetes 17,19,26 .…”

Section: Introductionmentioning

confidence: 99%

“…16 The recent studies have attempted to clarify the metabolic-related testosterone decline in diabetes due to whether testicular, hypothalamus or pituitary defects. 15,25 Hypogonadotropic hypogonadism (HH) is the major form of secondary hypogonadism and previous documents suggested that HH occurs commonly in young and middle-aged male type 2 diabetes. 17,19,26 Nearly one-third of American men with type 2 diabetes have low testosterone concentrations along with inappropriately low LH and FSH concentrations.…”

Section: Introductionmentioning

confidence: 99%

The occurrence of hypogonadotropic hypogonadism in Chinese men with type 2 diabetes

Zhou

Tian

Wang

et al. 2022

Clinical Endocrinology

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Context The previous studies showed that hypogonadotropic hypogonadism (HH) occurred commonly in men with type 2 diabetes. However, since all the cohorts tested were from American and European studies, the occurrence of HH/nongonadal illness (NGI) in Chinese populations is unclear. Objective The study aimed to explore the occurrence of HH/NGI in Chinese men with type 2 diabetes. Furthermore, the correlative factors and predictors of hypogonadism were investigated. Design We conducted a cross‐sectional study of 637 Chinese men with type 2 diabetes aged 20–75 years in our clinic. The prevalence of HH/NGI was investigated by measuring serum total testosterone (TT), sex hormone‐binding globulin (SHBG), luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) in the enrolled subjects. Free testosterone (FT) was calculated by using SHBG and TT levels and hypogonadism was defined as TT lower than 10.4 nmol/L and calculated FT (cFT) lower than 0.225 nmol/L. The LH cut‐off value for defining HH/NGI was 9.4 mIU/ml. Results The results suggested that 31.9% of male Chinese type 2 diabetes patients had hypogonadism and 26.5% of subjects in our cohort were determined as HH/NGI. The occurrence of hypogonadism was markedly correlated with body mass index (BMI). There was a significant association between TT, cFT and SHBG levels with BMI. TT levels are inversely correlated with BMI and homeostasis model assessment‐estimated insulin resistance (HOMA‐IR) while positively related with SHBG. The cFT levels were inversely correlated with age, LH, FSH, BMI and HOMA‐IR. Multiple regression analysis suggested that SHBG, BMI and HOMA‐IR were significant predictors of TT and cFT. Conclusion Our present study offered the first evidence that the occurrence of HH/NGI in Chinese male type 2 diabetes was 26.5%. TT and cFT were significantly correlated with BMI, SHBG and HOMA‐IR in Chinese men with type 2 diabetes.

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Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms

Cited by 36 publications

References 30 publications

Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

A systematic review on the role of melatonin and its mechanisms on diabetes-related reproductive impairment in non-clinical studies

The occurrence of hypogonadotropic hypogonadism in Chinese men with type 2 diabetes

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