Basic and Translational ScienceAltered Expression and Localization of Estrogen Receptors Alpha and Beta in the Testes of a Cryptorchid Rat Model
Section snippets
Animals
All experimental procedures were performed in accordance with protocols approved by the Animal Care Committee of the Faculty of Medicine, Nagoya City University. To generate cryptorchid rats, pregnant Sprague-Dawley (S-D) rats were exposed to flutamide, as described previously.11 In brief, each rat was administered 7.5 mg/d flutamide, and male offspring with unilateral cryptorchidism were used as model rats for subsequent experiments. Their testes were removed 4, 5, 7, and 10 weeks after birth
Results
Gene expression values of ERalpha and ERbeta in the cryptorchid testes and contralateral descended testes are shown in Figure 1. In the descended testes, gene expression increased with growth and peaked at 7 weeks (expression levels at 7 weeks were significantly different compared with those at 4 and 5 weeks, P <.05). When the rats were 10 weeks old, gene expression decreased but the decrease was not significant. Compared with the descended testes, gene expression decreased in the cryptorchid
Comment
Spermatogenic impairment is a serious complication of cryptorchidism, and according to paternity data, a large cohort study revealed that 10% to 38% of patients with cryptorchidism were infertile.16 Although the mechanisms underlying the inhibition of spermatogenesis in cryptorchidism have not been completely elucidated, we consider that the undescended status of the testes has direct and indirect multifactorial influences on testicular development. Since Eddy et al reported that male mice
Conclusions
We focused on ERalpha and ERbeta expression in cryptorchid testes and performed molecular and histologic analysis. Because of spermatogenic arrest at the spermatid differentiation stage, ERalpha expression in round and elongated spermatids is decreased, and spermatogenesis partially recovers after early orchiopexy. We considered that increased expression of ERalpha in Leydig cells of cryptorchid testes is associated with estradiol level in the testicular tissue, and androgen-estrogen imbalance
References (28)
- et al.
Estrogen receptor-alpha and beta are differentially distributed, expressed and activated in the fetal genital tubercle
J Urol
(2007) - et al.
A molecular basis for estrogen-induced cryptorchidism
Dev Biol
(2000) - et al.
Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation
Mol Cell Endocrinol
(2001) - et al.
Environmental effects on hormonal regulation of testicular descent
J Steroid Biochem Mol Biol
(2006) - et al.
Estradiol represses insulin-like 3 expression and promoter activity in ma-10 Leydig cells
Toxicology
(2009) - et al.
Early orchiopexy improves subsequent testicular development and spermatogenesis in the experimental cryptorchid rat model
J Urol
(2008) - et al.
Activation of NF-kappaB associated with germ cell apoptosis in testes of experimentally induced cryptorchid rat model
Urology
(2009) - et al.
17 beta-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ER alpha
Mol Cell Endocrinol
(2010) - et al.
Neoadjuvant gonadotropin-releasing hormone therapy before surgery and effect on fertility index in unilateral undescended testes: a prospective randomized trial
Urology
(2009) - et al.
Hormonal status of male reproductive system: androgens and estrogens in the testis and epididymisIn vivo and in vitro approaches
Reprod Biol
(2006)
Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities
Hum Reprod
Estrogen receptor alpha is a major contributor to estrogen-mediated fetal testis dysgenesis and cryptorchidism
Endocrinology
Estrogen enhances recovery from radiation-induced spermatogonial arrest in rat testes
J Androl
Estrogen promotes germ cell and seminiferous tubule development in the baboon fetal testis
Biol Reprod
Cited by (21)
Differential abundances of AQP3 and AQP5 in reproductive tissues from dogs with and without cryptorchidism
2021, Animal Reproduction ScienceCitation Excerpt :In addition to androgens, oestrogens can regulate the development and function of the male reproductive tract (Hess et al., 1997; Cooke et al., 2017). The androgen-oestrogen imbalance can lead to suppression of spermatogenesis as a result of cryptorchidism (Mizuno et al., 2011). Hormonal alterations in the male reproductive system might be associated with altered AQP abundances and functions.
The expressions in oxytocin and sex steroid receptors in the reproductive tissues of normal and unilateral cryptorchid dogs
2017, TheriogenologyCitation Excerpt :The results from this study failed to detect the localization of ERα in the testis; therefore, this indicated that ERβ is the main and only subtype to mediate estrogenic action in the canine testis. On the other hand, a recent study showed that increased expression of ERα in Leydig cells of cryptorchid testes was associated with an alteration of spermatogenesis in cryptorchidism, while the expression of ERβ was unchanged [7]. In summary, the present study demonstrated the difference of OTR and sex steroid receptor expressions between normal and cryptorchid dogs.
Phospholipid hydroperoxide glutathione peroxidase is involved in the maintenance of male fertility under cryptorchidism in mice
2015, Reproductive ToxicologyCitation Excerpt :However, PHGPx immunostaining was slightly upregulated in interstitial degenerative Leydig cells under cryptorchidism until 21 days, as if PHGPx acts as an antioxidant enzyme for the damaged Leydig cells. Induction of cryptorchidism resulted in reduced intratesticular testosterone levels, but increased estrogen receptor levels in spermatids and Sertoli cells [34,41,42]. PHGPx gene is upregulated by estrogenic compounds via estrogen receptors in mouse embryo and rat testes [42,43].
Environmental oestrogens disrupt testicular descent and damage male reproductive health: Mechanistic insight
2023, Journal of Cellular and Molecular MedicineLoss of WNT4 in the gubernaculum causes unilateral cryptorchidism and fertility defects
2022, Development (Cambridge)