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Background: Insulin-like peptide 3 (INSL3) is a constitutive, secreted peptide produced in the male uniquely by the Leydig cells of the testes. It is a biomarker for Leydig cell functional capacity, which is a measure of the numbers and differentiation status of these steroidogenic cells and lacks the biological and technical variance of the steroid testosterone. This retrospective study was carried out to examine the relationship between seminal parameters and the Leydig cell compartment, and secondarily to assess other factors responsible for determining Leydig cell functional capacity.
Methods: INSL3 was assessed together with seminal, anthropometric, and hormonal parameters in a Swedish cohort of 18-year-old men, representing the average population, and in a smaller, more heterogeneous cohort of men visiting an Australian infertility clinic.
Results And Discussion: Average INSL3 concentration at 18 years is greater than that reported at younger or older ages and indicated a large 10-fold variation. In neither cohort was there a relationship between INSL3 concentration and any semen parameter. For the larger, more uniform Swedish cohort of young men, there was a significant negative relationship between INSL3 and BMI, supporting the idea that adult Leydig cell functional capacity may be established during puberty. In both cohorts, there was a significant relationship between INSL3 and FSH, but not LH concentration. No relationship was found between INSL3 and androgen receptor trinucleotide repeat polymorphisms, reinforcing the notion that Leydig cell functional capacity is unlikely to be determined by androgen influence alone. Nor did INSL3 correlate with the T/LH ratio, an alternative measure of Leydig cell functional capacity, supporting the view that these are independent measures of Leydig cell function.
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http://dx.doi.org/10.1111/andr.13001 | DOI Listing |
Hum Reprod
September 2025
Institut National de la Santé et de la Recherche Médicale, Ecole des Hautes Etudes en Santé Publique, Institut de recherche en santé, environnement et travail, Université de Rennes-UMR_S1085, Rennes, France.
Study Question: What is the direct effect of mumps virus (MuV) replication within the human testis on the tissue innate immune responses and testicular cell functions?
Summary Answer: MuV induces an early pro-inflammatory response in the human testis ex vivo and infects both Leydig cells and Sertoli cells, which drastically alters testosterone and inhibin B production.
What Is Known Already: Despite widespread vaccination efforts, orchitis remains a significant complication of MuV infection, especially in young men, which potentially results in infertility in up to 87% of patients with bilateral orchitis. Our understanding of MuV pathogenesis in the human testis has been limited by the lack of relevant animal models, impairing the development of effective treatments.
Toxicol Appl Pharmacol
September 2025
Department of Environmental Hygiene and Toxicology, School of Public Health, Wenzhou Medical University, Wenzhou 325035, China. Electronic address:
Phthalates (PEs) are widespread in environment, and human beings are unavoidably exposing to the mixture of PEs, which may induce male reproductive health risks. In order to investigate the mechanism of male reproductive injuries caused by the mixture of di-2-ethylhexyl phthalate, dibutyl phthalate and butyl benzyl phthalate (MPEs), male rats were orally exposed to 16 mg/kg/d MPEs (L-MPEs) and 450 mg/kg/d MPEs (H-MPEs) for 90 days, and the results showed that MPEs decreased the weights of testes, epididymis and periepididymis fat, decreased serum levels of male hormones, increased abnormal sperm rate, and caused testicular histopathological damages, such as atrophy and cavitation of seminiferous tubules, spermatids exfoliation, Leydig cells hyperplasia and accumulation of lipid droplets in the testicular interstitium. Testicular transcriptomic analysis identified 100 differently expressed genes (DEGs) in L-MPEs group and 10,880 DEGs in H-MPEs group, and these DEGs mainly involved in signaling pathways of focal adhesion, PI3K-Akt, AGE-RAGE, axon guidance, PPAR, MAPK and etc.
View Article and Find Full Text PDFIntroduction: Leydig cell tumors (LCTs), constituting 1%-3% of testicular tumors, are mostly benign, but malignant cases present treatment challenges. We report a malignant LCT case with a notable response to mitotane.
Case Presentation: A 43-year-old male presented with a right testicular induration and was diagnosed with a Leydig cell tumor following orchiectomy.
Menopause
September 2025
Atlantic Medical Group, Atlantic Health System, Division of Endocrinology, Overlook Medical Center, Atlantic Health System, Summit, NJ.
Objectives: Hyperandrogenism, while one of the most common endocrine disorders in women, is relatively uncommon in the postmenopausal population. When present, it may be indicative of an underlying rare androgen-secreting ovarian tumor. Here, we report 2 cases: a 63-year-old woman with 2 years of male-pattern baldness and hirsutism and a 71-year-old female with 2 years of progression to complete scalp alopecia, hirsutism, and libido changes.
View Article and Find Full Text PDFJ Lipid Res
August 2025
Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address:
Neuronal growth regulator 1 (NEGR1) has been identified as a critical risk factor for major depressive disorders in humans. Although NEGR1 is predominantly expressed in the brain, its deletion in mice (Negr1) results in abnormalities in peripheral tissues, suggesting a role beyond the nervous system, particularly in intracellular lipid trafficking. However, the role of NEGR1 in testosterone production has not yet been elucidated.
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