Curative GnRHa treatment has an unexpected repressive effect on Sertoli cell specific genes

Gegenschatz‐Schmid, Katharina; Verkauskas, Gilvydas; Demougin, Philippe; Bilius, Vytautas; Dasevičius, Darius; Stadler, Michael; Hadžiselimović, Faruk

doi:10.1186/s12610-018-0067-1

Cited by 13 publications

(9 citation statements)

References 84 publications

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“…Of interest, 4 genes localized in the male-specific Y region, RBMY1B , RB-MY1E , RBMY1J , and TSPY4 , show reduced mRNA levels in HIR samples and also positively responded to GnRHa treatment. This observation supports data of global conservations of the epigenetic pattern associated with the sequences of the same origin (X-transposed, X-degenerate, and ampliconic) [Gegenschatz-Schmid et al, 2018]. …”

Section: Germ and Sertoli Cell Gene Stimulation By Gnrh Treatmentsupporting

confidence: 77%

Is Hormonal Treatment of Congenital Undescended Testes Justified A Debate

Hadžiselimović¹

2019

Sex Dev

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Abnormal germ cell development in cryptorchidism is not a result of a congenital dysgenesis but is preceded by a hormone imbalance and perturbation in germ cell-specific gene expression during abrogated mini-puberty. Adequate treatment with low doses of GnRHa enables 86% of men to achieve a normal sperm count and, most importantly, prevent development of azoospermia. GnRHa treatment induces a significant transcriptional response, including protein coding genes involved in pituitary development, the hypothalamic-pituitary-gonadal axis, and testosterone synthesis. Furthermore, hormonal treatment to achieve epididymo-testicular descent as a first choice of treatment of cryptorchidism has a long tradition in Europe. It eliminates the necessity of subsequent surgery. Moreover, in the cases of non-responders it facilitates orchidopexy and contributes considerably to a reduced incidence of unilateral and the more serious bilateral complete post-surgical testicular atrophy.

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Section: Germ and Sertoli Cell Gene Stimulation By Gnrh Treatmentsupporting

confidence: 77%

Is Hormonal Treatment of Congenital Undescended Testes Justified A Debate

Hadžiselimović¹

2019

Sex Dev

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“…Intriguingly, a study reported that the early postnatal rise of inhibin B at 3 months of age was positively correlated with LH and testosterone and was negatively correlated with FSH [Main et al, 2006]. There has been raised the possibility that Sertoli cell proliferation during mini-puberty depends more on LH and secondary testosterone than on FSH [Gegenschatz-Schmid et al, 2018]. From mid-puberty and onwards in adulthood, inhibin B correlates negatively with FSH [Crofton et al, 2002].…”

Section: Discussionmentioning

confidence: 97%

“…To emphasize if inhibin B is a promising tool in the evaluation of fertility, this correlation indeed needs more research. The transformation of gonocytes into Ad spermatogonia has been suggested to be initiated by elevated FSH, LH, and testosterone, as gonadotropinreleasing hormone (GnRH) stimulation before and after orchiopexy in cryptorchid boys had a higher number of Ad spermatogonia versus those who did not receive stimulation [Gegenschatz-Schmid et al, 2018]. Overall, this implies that the maturation of spermatogonia fails in cryptorchid testes and may result in a loss in the total number of germ cells, indicating that the potential for male fertility may be established in mini-puberty, during a period between 1 and 3 postnatal months, where transformation of gonocytes into Ad spermatogonia takes place.…”

Section: Discussionmentioning

confidence: 99%

Sertoli Cell Number Correlates with Serum Inhibin B in Infant Cryptorchid Boys

Hildorf¹,

Dong²,

Thorup³

et al. 2019

Sex Dev

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Postnatal maturation of Sertoli cells is crucial for male fertility. The aim of this study was to assess the association between the Sertoli cell number per tubule cross-section (SC/T), the serum level of the Sertoli cell-produced inhibin B, and the A-dark spermatogonia number per tubule (Ad/T) in cryptorchid boys. Forty infant cryptorchid boys aged 4-35 months (median: 13 months) were included in the study. During orchiopexy, blood samples for serum inhibin B, luteinizing hormone (LH), and follicle stimulating hormone (FSH) and testicular biopsies were obtained. Histological sections were evaluated by quantitative immunohistochemical and immunofluorescence analysis including VASA and SOX9 (Sertoli cell marker) in order to measure the tubular germ cell number (G/T), Ad/T, and SC/T. The SC/T correlated negatively with age (p < 0.0002) and positively with G/T, Ad/T, inhibin B, FSH, and LH (all p < 0.01). Inhibin B correlated with LH (p < 0.0001), but not with FSH (p = 0.2077). The SC/T:G/T ratio positively correlated with age (p < 0.0001). Boys with Ad spermatogonia at surgery had a higher number of Sertoli cells compared to boys without Ad spermatogonia. In conclusion, a correlation between Sertoli cell number and inhibin B was proven, indicating that inhibin B possibly reflects the function of Sertoli cells in infant cryptorchid boys.

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“…The administration of gonadotropins is safe, well tolerated and effective. Finally, new evidences suggest also the possibility of treatment with a gonadotropin-releasing hormone agonist, which induces gonocytes to differentiate into Ad spermatogonia and rescues fertility ( 84 ). As regards hypergonadotropic hypogonadism, one of the most frequent causes is Turner syndrome (TS).…”

Section: Minipuberty and Hypogonadismmentioning

confidence: 99%

Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary-Gonadal Axis Activation in Fetal and Neonatal Life

et al. 2018

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Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3–6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.

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Curative GnRHa treatment has an unexpected repressive effect on Sertoli cell specific genes

Cited by 13 publications

References 84 publications

Is Hormonal Treatment of Congenital Undescended Testes Justified A Debate

Is Hormonal Treatment of Congenital Undescended Testes Justified A Debate

Sertoli Cell Number Correlates with Serum Inhibin B in Infant Cryptorchid Boys

Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary-Gonadal Axis Activation in Fetal and Neonatal Life

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