Effects of concomitant diabetes mellitus and hyperthyroidism on testicular and epididymal histoarchitecture and steroidogenesis in male animals

Abstract

This study evaluated the effects of comorbid disorders of diabetes and hyperthyroidism in the adult male mice. In total, 32 ICR strain mice were equally distributed into four groups: control (C), diabetic (D), diabetic-plushyperthyroid (DH), and hyperthyroid (H). Mice allocated for diabetes received a single intraperitoneal injection of streptozotocin (STZ) at 200 mg/kg body weight. At the onset of diabetes, one group of mice was concomitantly injected levothyroxine (LT4; 0.3 mg/kg body weight) and the other set of animals received the same treatment independently on a daily basis. The body weight, as well as the testicular and epididymal weights, was reduced markedly in D and DH mice. Higher trends of blood glucose levels were seen in the DH group, in comparison to euthyroid diabetic mice. Thyroid hormones could exert a transient effect on blood glucose homeostasis by altering the serum blood glucose level in diabetic patients. Histomorphometric analysis showed increased luminal sizes of seminiferous tubules, along with decreased epithelial height and atrophic changes in germinal stem cells in the testis of DH and H mice. Caput epididymis of DH mice showed extensive compaction of principal cells, loss of stereocilia, lipid vacuolization, and inflammatory infiltrations; however, damaged tubular integrity, packed clear cells, exfoliated cells, and round spermatids were profoundly noticed in the cauda epididymis. Hyperthyroidism elevated the serum testosterone levels in H and DH mice and produced critical damages to the histoarchitecture of the epididymis. Collectively, this experiment endeavored to mimic the polyglandular autoimmune syndrome, which will be helpful to better understand the reasons for male infertility in diabetic-cum-hyperthyroid patients.

Effects of hyper‐ and hypothyroidism on the development and proliferation of testicular cells in prepubertal rats

“…; Mendis‐Handagama & Ariyaratne ; Holsberger & Cooke ; Korejo et al . ). Modern studies have suggested a close association between reproductive failure exemplified by altered semen quality and sub‐normal sperm count and motility with hypo‐ and hyperthyroid states.…”

“…This leads to a decrease in serum luteinizing hormone (LH) and testosterone concentration (Zirkin et al 1980;Mendis-Handagama et al 1991). In addition, studies have shown that thyroid hormones are responsible for regulating and developing testicular function by controlling the action of Sertoli cells and Leydig cells, which are involved in the regulation of testicular size Mendis-Handagama & Ariyaratne 2001;Holsberger & Cooke 2005;Korejo et al 2016). Modern studies have suggested a close association between reproductive failure exemplified by altered semen quality and sub-normal sperm count and motility with hypo-and hyperthyroid states.…”

Impact of diabetic hyperglycaemia and insulin therapy on autophagy and impairment in rat epididymis

“…Previous clinical and animal experimental data have proved that diabetic hyperglycaemia can disrupt male reproductive function, and male infertility and sexual dysfunction are considered to be common diabetic complications (Hylmarova et al., 2020; Maresch et al., 2018; Shi et al., 2017). Currently, there are few studies on the effects of diabetic hyperglycaemia on epididymis (Korejo et al., 2016; Singh et al., 2009). In this study, tissue morphological analysis showed that damage to epididymal tissues was apparent in the DM group and INS treatment could significantly alleviate epididymal damage, which was consistent with the effects on epididymal secretory products by diabetic and insulin therapy (Singh et al., 2009).…”

“…Currently, research on DM‐induced reproductive dysfunction is focused on the testes and sperm quality (Condorelli et al., 2018; Ding et al., 2015) and there are fewer studies on damage to epididymal structure and function (Maresch et al., 2018). Histological studies have found that the epididymal tissues of DM rats undergo significant pathological degenerative changes (Korejo et al., 2016) as well as secretory dysfunction (Singh et al., 2009), but the specific damage mechanisms are still unknown. The epididymis is the site of sperm transportation, storage and maturation, so the adverse effects of DM on epididymal structure and function should have an impact on sperm quality.…”

Oral Exposure to Genistein during Conception and Lactation Period Affects the Testicular Development of Male Offspring Mice

“…Pathological sections were prepared, as described in the previous report [40]. Testicular samples were fixed in 10% formaldehyde solution for 24 h. Fixed tissues were dehydrated in a graded series of alcohol, rendered transparent in xylene, and embedded in paraffin.…”