1.Androgen receptors are expressed in a variety of human fetal extragenital tissues: an immunohistochemical study.
Yasmin SAJJAD ; Siobhan QUENBY ; Paul NICKSON ; David Iwan LEWIS-JONES ; Gill VINCE
Asian Journal of Andrology 2007;9(6):751-759
AIMTo investigate the expression of androgen receptors in the extragenital tissues of developing human embryo.
METHODSUsing immunohistochemistry, we investigated the distribution of androgen receptor (AR) in the extragenital tissues of paraffin-embedded tissue sections of first trimester (8-12 weeks gestation) human embryos. Gender was determined by polymerized chain reaction.
RESULTSThere were no differences in the expression and distribution of AR in male and female embryos at any stage of gestation. AR expression was seen in the thymus gland. The bronchial epithelium of the lungs showed intense positive staining with surrounding stroma negative. Furthermore, positive staining for androgen receptor was exhibited in the spinal cord with a few positive cells in the surrounding tissues. Cardiac valves also showed strong positive staining but with faint reactivity of the surrounding cardiac muscle. There was no staining in kidney, adrenal, liver or bowel.
CONCLUSIONThis study demonstrates that immunoreactive AR protein is present in a wide variety of human first trimester fetal tissues and shows the potential for androgen affecting tissues, which are mostly not considered to be androgen dependent. Moreover, it implies that androgen might act as a trophic factor and affect the early development of these organs rather than simply sexual differentiation.
Bronchi ; cytology ; embryology ; metabolism ; Female ; Fetus ; cytology ; metabolism ; Heart ; embryology ; Humans ; Immunohistochemistry ; methods ; Male ; Myocardium ; cytology ; metabolism ; Pregnancy ; Pregnancy Trimester, First ; Receptors, Androgen ; genetics ; metabolism ; Spinal Cord ; cytology ; embryology ; metabolism ; Thymus Gland ; cytology ; embryology ; metabolism
2.Novel association between sperm deformity index and oxidative stress-induced DNA damage in infertile male patients.
Tamer M SAID ; Nabil AZIZ ; Rakesh K SHARMA ; Iwan LEWIS-JONES ; Anthony J THOMAS ; Ashok AGARWAL
Asian Journal of Andrology 2005;7(2):121-126
AIMTo investigate the impact of abnormal sperm morphology using the sperm deformity index (SDI) on reactive oxygen species (ROS) production and its correlation with sperm DNA damage.
METHODSSemen samples were collected from men undergoing infertility screening (n = 7) and healthy donors (n = 6). Mature spermatozoa were isolated and incubated with 5 mmol/L beta-nicotinamide adenine dinucleotide phosphate (NADPH) for up to 24 h to induce ROS. Sperm morphology was evaluated using strict Tygerberg's criteria and the SDI. ROS levels and DNA damage were assessed using chemiluminescence and terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL) assays, respectively.
RESULTSSDI values (median [interquartiles]) were higher in patients than donors (2 [1.8, 2.1] vs. 1.53 [1.52, 1.58], P = 0.008). Aliquots treated with NADPH showed higher ROS levels (1.22 [0.30, 1.87] vs. 0.39 [0.10, 0.57], P = 0.03) and higher incidence of DNA damage than those not treated (10 [4.69, 24.85] vs. 3.85 [2.58, 5.10], P = 0.008). Higher DNA damage was also seen following 24 h of incubation in patients compared to donors. SDI correlated with the percentage increase in sperm DNA damage following incubation for 24 h in samples treated with NADPH (r = 0.7, P = 0.008) and controls (r = 0.58, P = 0.04).
CONCLUSIONSDI may be a useful tool in identifying potential infertile males with abnormal prevalence of oxidative stress (OS)-induced DNA damage. NADPH plays a role in ROS-mediated sperm DNA damage, which appears to be more evident in infertile patients with semen samples containing a high incidence of morphologically abnormal spermatozoa.
DNA Damage ; Humans ; Infertility, Male ; genetics ; pathology ; Male ; Oxidative Stress ; Reactive Oxygen Species ; Spermatozoa ; abnormalities