Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*

Approximately 15% of men in the general population have varicoceles, and varicoceles are diagnosed in 40% of men presenting for fertility evaluations. One percent of men in the general population are azoospermic, and 15% of men presenting for fertility evaluations are diagnosed with azoospermia. This article aims to review the impact of varicoceles on testicular function in men with azoospermia, the impact of varicocele repair on the semen parameters of azoospermic men, and the impact of varicocele repair on sperm retrieval and pregnancy outcomes when the male partner remains azoospermic after varicocele repair.
Humans ; Varicocele/physiopathology* ; Azoospermia/physiopathology* ; Male ; Pregnancy ; Female ; Sperm Retrieval ; Semen Analysis ; Pregnancy Outcome ; Testis/physiopathology*

The adverse effects of obesity on male reproductive function are mainly manifested as the abnormal development of the reproductive system, decrease of testosterone level, decline of sperm quality, and impact on the health of offspring, while its regulatory mechanism is far from being clarified. This paper expounds the influence of obesity on the male reproductive system in the aspects of population epidemiology and animal experiments, presents an overview on the action mechanisms of obesity from the perspectives of the hypothalamus-pituitary-testis axis, blood-testis barrier, inflammatory reaction, oxidative stress, testicular germ cell apoptosis, and impact of paternal obesity on the health of offspring, aiming to shed some light on the clinical treatment and prevention of obesity-related male reproductive dysfunction.
Male ; Obesity/physiopathology* ; Humans ; Animals ; Hypothalamo-Hypophyseal System ; Testis/physiopathology* ; Oxidative Stress ; Infertility, Male/etiology* ; Reproduction ; Blood-Testis Barrier

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.
Animals ; Biomarkers ; Endocrine Disruptors/toxicity* ; Environmental Exposure/adverse effects* ; Environmental Pollutants/toxicity* ; Hypothalamo-Hypophyseal System/physiopathology* ; Infertility, Male/physiopathology* ; Male ; Phenols/toxicity* ; Rats ; Rats, Sprague-Dawley ; Sulfones/toxicity* ; Testis/physiopathology* ; Toxicity Tests, Chronic

Objective: To investigate the influence of different procedures of testicular sperm retrieval on the levels of serum inhibin B (INHB), antisperm antibodies (AsAb), follicle-stimulating hormone (FSH), and testosterone (T) in patients with azoospermia. METHODS: We randomly assigned 210 azoospermia patients to receive testicular sperm extraction (TESE, n = 50), testicular sperm aspiration (TESA, n = 56), testicular fine needle aspiration (TEFNA, n = 64), or microscopic TESE (micro-TESE, n = 40). We measured the levels of serum INHB, FSH, and T and the positive rate of AsAb before and at 1 and 3 months after surgery. RESULTS: Compared with the baseline, the levels of serum FSH at 1 and 3 months after surgery showed no statistically significant differences in the TESE (［8.51 ± 4.34］ vs ［8.76 ± 3.07］ and ［7.24 ± 3.32］ IU/L, P >0.05), TESA (［7.70 ± 2.72］ vs ［7.90 ± 4.57］ and ［8.04 ± 3.65］ IU/L, P >0.05), TEFNA (［6.04 ± 3.17］ vs ［6.08 ± 2.70］ and ［6.10 ± 3.32］ IU/L, P >0.05), or micro-TESE group (［6.59 ± 2.74］ vs ［6.89 ± 1.78］ and ［6.75 ± 2.57］ IU/L, P >0.05); the positive rate of AsAb (IgM) was significantly increased at 1 month in the TESE (0.00 vs 14.00%, P <0.05) and micro-TESE groups (2.50% vs 15.00%, P <0.05), while the serum T level markedly decreased in the two groups (［16.52 ± 6.25］ vs ［9.25 ± 5.76］ nmol/L and ［14.16 ± 5.45］ vs ［8.23 ± 4.12］ nmol/L, P <0.05); the levels of serum INHB were remarkably reduced at 1 and 3 months in the TESE (［70.56 ± 23.17］ vs ［42.63 ± 15.34］ and ［44.05 ± 18.47］ pg/ml, P <0.05), TESA (［68.71 ± 14.74］ vs ［40.55 ± 20.51］ and ［42.11 ± 19.34］ pg/ml, P <0.05), TEFNA (［76.81 ± 27.04］ vs ［46.31 ± 19.28］ and ［48.32 ± 20.54］ pg/ml, P <0.05), and micro-TESE groups (［74.74 ± 28.35］ vs ［45.27 ± 18.83］ and ［47.64 ± 28.34］ pg/ml, P <0.05), but with no statistically significant differences among the four groups (P >0.05). CONCLUSIONS Different procedures of testicular sperm retrieval have different impacts on the testicular function and AsAb in patients with azoospermia.
Antibodies ; blood ; Azoospermia ; blood ; physiopathology ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; blood ; Male ; Sperm Retrieval ; Spermatozoa ; immunology ; Testis ; metabolism ; physiopathology ; Testosterone ; blood

ObjectiveTo investigate the influence of unilateral cryptorchidism on the levels of serum anti-müllerian hormone (AMH) and inhibin B in children.

METHODSWe enrolled 65 patients with unilateral cryptorchidism and 45 healthy children in this study. We measured the length and circumference of the penis, the testis volume in the cryptorchidism side, and the levels of serum AMH and inhibin B at the age of 6 and 12 months, respectively.

RESULTSCompared with the healthy controls, the patients with unilateral cryptorchidism showed significant decreases at 12 months in serum AMH (［108.06±12.40］ vs ［103.26±17.57］ ng/ml, P<0.05) and inhibin B (［77.43±5.66］ vs ［70.21±5.69］ pg/ml, P<0.05). No statistically significant differences were found in the length and circumference of the penis and the testis volume in the cryptorchidism side at 6 and 12 months (P>0.05), or in the levels of serum AMH and inhibin B at 6 months (P>0.05).

CONCLUSIONSUnilateral cryptorchidism affects the gonadal function of the patient, and orchiopexy should be timely performed in order to reduce its impact.

Anti-Mullerian Hormone ; blood ; Case-Control Studies ; Cryptorchidism ; blood ; pathology ; Humans ; Infant ; Inhibins ; blood ; Male ; Orchiopexy ; Organ Size ; Penis ; pathology ; Testis ; pathology ; physiopathology ; Transforming Growth Factor beta

ObjectiveTo explore the effects of ischemic preconditioning on the level of serum testosterone (T) and apoptosis of spermatogenic cells in rabbits with testicular ischemia-reperfusion injury induced by testicular torsion.

METHODSA total of 15 New Zealand male rabbits were randomly divided into groups A (control), B (ischemia-reperfusion), and C (ischemic preconditioning). The animals of group A were subjected to exposure of the right spermatic cord without ischemia, those of group B received 60-minute non-invasive occlusion of the right spermatic cord followed by 3 days of reperfusion, and those of group C underwent 5-minute occlusion plus 5-minute reperfusion of the right spermatic cord followed by the same procedure as that for group B. Then the rabbits were narcotized with 3% barbital sodium, the whole blood collected for examination of the serum T content and the testis tissues obtained from both the ischemic and healthy sides for HE and TUNEL staining.

RESULTSAfter operation, the body weight was significantly increased as compared with the baseline in groups A (［2.65±0.07］ vs ［2.45±0.07］ kg, P<0.05) and C (［3.03±0.11］ vs ［2.92±0.07］ kg, P<0.05), but not in group B (［3.05±0.07］ vs ［3.05±0.07］ kg, P>0.05). The serum T level showed no statistically significant difference in group A before and after operation (［139.59±9.39］ vs ［140.19±9.47］ ng/L, P>0.05), but was remarkably lower after operation than the baseline in groups B ［148.06±3.31］ vs ［74.12±4.00］ ng/L, P<0.01) and C (［133.75±6.48］ vs［94.76±3.13］ ng/L, P<0.01) as well as than the postoperative index in group A (P<0.01). In comparison with group A and the healthy side of group B, the testis tissue of the ischemic side in group B exhibited structural damage of most of the seminiferous tubules with disappearance of spermatogenic cell structures, apoptosis of spermatogenic cells, and exudation of light-eosin edema fluid in the mesenchyme and lumen, with a markedly increased apoptosis index (P<0.01) and a significantly decreased Johsen's score (P<0.01). Compared with ischemic side of group B, The testis tissue of the ischemic side in group C was restored to normal as compared with that in group B, with a dramatically decreased apoptosis index (P<0.01) and a remarkably increased Johnsen's score (P<0.01).

CONCLUSIONSIschemic preconditioning can raise the decreased serum T level and reduce the apoptosis of spermatogenic cells in rabbits with testicular ischemia-reperfusion injury, which could be applied as a potential option for the clinical treatment of testicular ischemia-reperfusion injury.

Animals ; Apoptosis ; Germ Cells ; In Situ Nick-End Labeling ; Ischemia ; physiopathology ; Ischemic Preconditioning ; Male ; Rabbits ; Random Allocation ; Reperfusion Injury ; blood ; physiopathology ; Spermatic Cord Torsion ; Testis ; physiopathology ; Testosterone ; blood

Objective To summarize the clinical features of XO/XY gonadal dysgenesis. Method We retrospectively analyzed the clinical data of patients with XO/XY gonadal dysgenesis admitted to Peking Union Medical College Hospital from January 2008 to May 2015. Results Totally 32 patients with XO/XY gonadal dysgenesis were included. The social gender was female in all subjects and the age 6 to 33 years. Patients presented mainly with primary amenorrhea or short stature,and usually had specific somatic signs of Turner's syndrome. The breast development of 27 patients (84.38%) was less than level 3. The armpit hair was sparse or absent in 28 patients (87.5%) and the pubic hair was sparse or absent in 26 patients (81.25%).Other findings include naive vulva (n=18,56.25%)) and enlarged clitoris (n=5,15.63%). The average level of follicle stimulating hormone was (78.56±35.62) mIU/ml,the luteinizing hormone level was (20.23±11.35) mIU/ml,the estradiol level was (9.94±8.21) pg/ml,and the testosterone level was (0.24±0.18) ng/ml. All patients received prophylactic gonadectomy. The histopathology results showed a variety of gonads,and gonadal malignancy were observed in 4 patients.Conclusions Patients with XO/XY gonadal dysgenesis manifest primary amenorrhea or short stature,poorly developed secondary sexual characteristics,and elevated gonadotropin level. The gonads have increased risk of gonadal malignancy.
Adolescent ; Adult ; Child ; Estradiol ; blood ; Female ; Follicle Stimulating Hormone ; blood ; Gonadal Dysgenesis, 46,XY ; physiopathology ; Humans ; Luteinizing Hormone ; blood ; Retrospective Studies ; Testis ; abnormalities ; physiopathology ; Testosterone ; blood ; Turner Syndrome ; physiopathology ; Young Adult

OBJECTIVETo evaluate the current status of penis and testicular development in boys and the effects of overweight/obesity on their development in the Zhengzhou area of Henan Province.

METHODSHeight, weight, waist circumference, hip circumference, penis length and testicular volume were measured in 3 546 4 to 12-year-old boys. The penis length and testicular volume were compared between the overweight/obesity and normal weight groups.

RESULTSBefore 9 years of age, the testicular volume was progressively smaller, and after 9 years old, it gradually increased. By the age of 11, it increased rapidly. The penis length increased gradually between 4 and 11 years of age, and after the age of 11 it increased rapidly. Phimosis was found in 144 cases (4.01%) and cryptorchidism was found in 18 cases (0.51%). A total of 639 (18.02%) boys were overweight or obese among 3 546 boys. At the ages of 6 and 7 years, the testicular volume in the overweight/obesity group was greater than in the normal control group (P<0.05). The penis length in the overweight/obesity group was significantly shorter than in the normal control group (P<0.05) by the age of 11 years. The correlation analysis showed that the testicular volume at the ages of 4 and 5 years was positively correlated with height, weight, BMI, waist circumference and hip circumference in overweight/obese boys. The penis length at the ages of 7 and 8 years was negatively correlated with weight, waist circumference and hip circumference. By the age of 12 years, the penis length was positively correlated with the height.

CONCLUSIONSThe development of penis and testicles in boys in the Zhengzhou area is in line with the level of sex development of Chinese boys. Overweight/obesity adversely affects the development of penis and testicles.

Child ; Child, Preschool ; China ; Humans ; Male ; Obesity ; epidemiology ; physiopathology ; Overweight ; epidemiology ; physiopathology ; Penis ; growth & development ; Testis ; growth & development