hCG treatment raises H2O2 levels and induces germ cell apoptosis in rat testis

Abstract

The clinical significance of exogenous hCG treatment is to stimulate steroidogenesis and spermatogenesis in the testis. However, the pathogenesis of detrimental effects on the testis arising out of chronic hCG treatment is yet to be clearly ascertained. In the present study we have shown that hCG treatment (100 IU/day) to rats for 30 days raises testicular oxidative stress leading to germ cell apoptosis and impairment of spermatogenesis. The treatment raises testicular H(2)O(2) levels along with increase in lipid peroxidation and concomitant decrease in the enzymatic antioxidant activities like superoxide dismutase, catalase and glutathione-s-transferase. The rise in the number of apoptotic germ cells was associated with up regulation of Fas protein expression and caspase-3 activity in the testis. However, serum testosterone which was elevated by 15 days of hCG treatment declined to pretreatment levels by 30 days. No significant alteration in serum gonadotropins was observed. The above findings indicate that the pathogenesis of deleterious effects following chronic hCG treatment is due to increase in testicular oxidative stress with high H(2)O(2) availability leading to apoptosis among germ cells.

SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells

“…Various environmental factors such as elevated scrotal temperature and oxidative stress have been linked to abnormal spermatogenesis and infertility (Anderson et al 1983, Emanuele & Emanuele 1998, Lue et al 2000, Rockett et al 2001, Dare et al 2002, Agarwal et al 2003, Aitken & Baker 2006, Gautam et al 2007, Aitken & Roman 2009, Shiraishi et al 2010 Figure 5 SUMO1 localizes to H 2 O 2 -induced DNA double-strand breaks in meiotic spermatocytes. Control (A 1 -A 4 ) and H 2 O 2 -treated (100 mM, 20 min B 1 -B 4 ) spermatocytes were co-immunolabeled using anti-gH2AX (red) and anti-SUMO1 (green) antibodies.…”

Antioxidant Systems and Oxidative Stress in the Testes

“…95 Interestingly, over-stimulation of the Leydig cells by chronic exposure to hCG (100 IU/day for 30 days in rats) also stimulates high levels of ROS production from these cells, that in turn stimulate lipid peroxidation, reduction in antioxidant enzyme activities, germ cell apoptosis and the consequential disruption of spermatogenesis. 98 Thus, as we saw with the involvement of the thyroid gland in the control of testicular function, a stable redox environment depends on an appropriately balanced gonadotrophic support, either hyper-or hypo-gonadotrophism will induce a state of oxidative stress in the testis.…”

Evaluation of Prolidase Activity, Oxidative Stress, and Antioxidant Enzyme Levels in Testicular and Penile Tissues after Human Chorionic Gonadotropin Treatment in Rats by Predicting Infertility and Erectile Dysfunction

“…The use of hCG is reported to have noxious effects which can lead to male infertility due to impaired spermatogenesis because of an increase in free oxygen radicals [2, 22]. To the best of our knowledge, no other studies in the literature have studied the effects of hCG treatment on prolidase activity, oxidative stress, and antioxidant enzyme levels in the testes and penile tissue.…”

“…Gautam et al [2] reported an increase in apoptosis in testicular germ cells and associated this with high oxidative stress and H 2 O 2 which is a sign of low antioxidant activity. Ozbek et al [26] found a significant increase in the number of giant cells and degenerated and desquamated cells in a testicular ischemia/reperfusion injury model.…”

“…hCG induces superovulation in females and is used to increase pregnancy rates by enhancing the number of oocytes and embryos, while it is used for the treatment of hypogonadotropic hypogonadism and cryptorchidism in males [1]. Although the use of hCG has beneficial effects like provocation of maturation of the seminiferous epithelium, facilitation of testicular descent and growth, improvement of sperm quality, and regaining of fertility by hypogonadotropic hypogonadism, it may also increase intravascular leucocytes and free oxygen radicals depending on the time of application and the dose, which causes deterioration of spermatogenesis and may lead to infertility [2]. …”