Chitosan/Selenium Nanoparticles Attenuate Diclofenac Sodium-Induced Testicular Toxicity in Male Rats

The detrimental effect of diclofenac sodium (Diclo-Na) on male reproductive organs is reported upon in this paper. Chitosan is a polysaccharide composed of various amounts of glucosamine. Chitosan nanoparticles (CH-NPs) have attracted much attention owing to their biomedical activity. Selenium (Se) has a vital role in nutrition, plays an important role in enhancing male reproduction, and has a wide range of free radical scavenging activities. However, the study of the impact of chitosan nanoparticles in combination with Se (IV) (CH-NPs/Se) on male reproductive toxicity associated with Diclo-Na administration is lacking in recent literature. The current study assessed the ameliorative effects of complexes of CH-NPs/Se (IV) on Diclo-Na and the ways in which they alter reproductive toxicity in male rats. Male rats were treated for 30 days successively, either with Diclo-Na (10 mg/kg) or co-treated with a CH-NPs/Se complex (280 mg/kg). Sperm characteristics, marker enzymes of testicular function, LH, FSH, and testosterone were evaluated in addition to oxidative stress markers and histological alterations. CH-NPs/Se significantly alleviated Diclo-Na-induced decline in sperm count and motility, testicular function enzymes, and levels of LH and testosterone in serum. Additionally, CH-NPs/Se co-administration at 280 mg/Kg, inhibited the Diclo-Na-induced decline of antioxidant enzyme activities and elevated oxidative stress indices and reactive free radicals in testicular homogenates of male rats. CH-NPs/Se (280 mg/kg) alone improved Diclo-Na and ameliorated histological damages in exposed rats. In conclusion, chitosan improved testicular function in Diclo-Na-treated rats by enhancing the testosterone hormone levels, ameliorating testicular tissue, and inhibiting markers of oxidative stress in male rats.

MAMLD1 and Differences/Disorders of Sex Development: An Update

<i>MAMLD1</i> (alias <i>CXorf6</i>) was first documented in 2006 as a causative gene of 46,XY differences/disorders of sex development (DSD). <i>MAMLD1</i>/<i>Mamld1</i> is expressed in the fetal testis and is predicted to enhance the expression of several Leydig cell-specific genes. To date, hemizygous <i>MAMLD1</i> variants have been identified in multiple 46,XY individuals with hypomasculinized external genitalia. Pathogenic <i>MAMLD1</i> variants are likely to cause genital abnormalities at birth and are possibly associated with age-dependent deterioration of testicular function. In addition, some <i>MAMLD1</i> variants have been identified in 46,XX individuals with ovarian dysfunction. However, recent studies have raised the possibility that <i>MAMLD1</i> variants cause 46,XY DSD and ovarian dysfunction as oligogenic disorders. Unsolved issues regarding MAMLD1 include the association between <i>MAMLD1</i> variants and 46,XX testicular DSD, gene-gene interactions in the development of <i>MAMLD1</i>-mediated DSD, and intracellular functions of MAMLD1.

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

Objectives: Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood. Methods: This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated. Results: Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14–16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT. Conclusion: Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.