Dataset Information

Downregulation of Sostdc1 in Testicular Sertoli Cells is Prerequisite for Onset of Robust Spermatogenesis at Puberty.

ABSTRACT: An alarming decline in sperm count of men from several countries has become a major concern for the world community. Hormones act on testicular Sertoli cells (Sc) to regulate male fertility by governing the division and differentiation of germ cells (Gc). However, there is a limited knowledge about Sc specific gene(s) regulating the spermatogenic output of the testis. Sclerostin domain-containing 1 protein (Sostdc1) is a dual BMP/Wnt regulator is predominantly expressed in the Sc of infant testes which hardly show any sign of spermatogenesis. In order to investigate the role of Sostdc1 in spermatogenic regulation, we have generated transgenic (Tg) rats which induced persistent expression of Sostdc1 in mature Sc causing reduced sperm counts. Although Sc specific Sostdc1 did not affect the function of either Sc or Leydig cells (Lc) in the adult testis of Tg rat, we observed a selective augmentation of the BMP target genes via activated phospho smad 1/5/8 signaling in Gc leading to apoptosis. Here, for the first time, we have demonstrated that Sostdc1 is a negative regulator of spermatogenesis, and provided substantial evidence that down regulation of Sostdc1 during puberty is critically essential for quantitatively and qualitatively normal spermatogenesis governing male fertility.

SUBMITTER: Pradhan BS

PROVIDER: S-EPMC6686024 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Downregulation of Sostdc1 in Testicular Sertoli Cells is Prerequisite for Onset of Robust Spermatogenesis at Puberty.

Pradhan Bhola Shankar BS Bhattacharya Indrashis I Sarkar Rajesh R Majumdar Subeer S SS

Scientific reports 20190807 1

An alarming decline in sperm count of men from several countries has become a major concern for the world community. Hormones act on testicular Sertoli cells (Sc) to regulate male fertility by governing the division and differentiation of germ cells (Gc). However, there is a limited knowledge about Sc specific gene(s) regulating the spermatogenic output of the testis. Sclerostin domain-containing 1 protein (Sostdc1) is a dual BMP/Wnt regulator is predominantly expressed in the Sc of infant teste ...[more]

PMID: 31391487

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Project description:BackgroundThe microscopic process of postnatal testicular development in early-puberty animals is poorly understood. Therefore, in this study, 21 male Yiling goats with average ages of 0, 30, 60, 90, 120, 150 and 180 days old (each age group comprised three goats) were used to study the changes in organs, tissues and transcriptomes during postnatal testicle development to obtain a broad and deep insight into the dynamic process of testicular transition from growth to spermatogenesis in early-puberty animals.ResultsThe inflection point of testicular weight was at 119 days postpartum (dpp), and the testicular weight increased rapidly from 119 dpp to 150 dpp. Spermatozoa were observed in the testis at 90 dpp by using haematoxylin-eosin staining. We found from the transcriptome analysis of testes that the testicular development of Yiling goat from birth to 180 dpp experienced three stages, namely, growth, transition and spermatogenesis stages. The goats in the testicular growth stage (0-60 dpp) showed a high expression of growth-related genes in neurogenesis, angiogenesis and cell junction, and a low expression of spermatogenesis-related genes. The goats aged 60-120 dpp were in the transitional stage which had a gradually decreased growth-related gene transcription levels and increased spermatogenesis-related gene transcription levels. The goats aged 120-180 dpp were in the spermatogenesis stage. At this stage, highly expressed spermatogenesis-related genes, downregulated testicular growth- and immune-related genes and a shift in the focus of testicular development into spermatogenesis were observed. Additionally, we found several novel hub genes, which may play key roles in spermatogenesis, androgen synthesis and secretion, angiogenesis, cell junction and neurogenesis. Moreover, the results of this study were compared with previous studies on goat or other species, and some gene expression patterns shared in early-puberty mammals were discovered.ConclusionsThe postnatal development of the testis undergoes a process of transition from organ growth to spermatogenesis. During this process, spermatogenesis-related genes are upregulated, whereas neurogenesis-, angiogenesis-, cell junction-, muscle- and immune-related genes are downregulated. In conclusion, the multipathway synergy promotes testicular transition from growth to spermatogenesis in early-puberty goats and may be a common rule shared by mammals.

Project description:This study aimed to determine the regulatory mechanism of bone morphogenetic protein 4 (BMP4) gene in the testes of Tibetan sheep and its role in the blood-testis barrier (BTB). First, we cloned BMP4 gene for bioinformatics analysis, and detected the mRNA and protein expression levels of BMP4 in the testes of Tibetan sheep pre-puberty (3-mo-old), during sexual maturity (1-yr-old), and in adulthood (3-yr-old) by qRT-PCR and Western blot. In addition, the subcellular localization of BMP4 was analyzed by immunohistochemical staining. Next, BMP4 overexpression and silencing vectors were constructed and transfected into primary Sertoli cells (SCs) to promote and inhibit the proliferation of BMP4, respectively. Then, CCK-8 was used to detect the proliferation effect of SCs. The expression of BMP4 and downstream genes, pathway receptors, tight junction-related proteins, and cell proliferation and apoptosis-related genes in SCs were studied using qRT-PCR and Western blot. The results revealed that the relative expression of BMP4 mRNA and protein in testicular tissues of 1Y group and 3Y group was dramatically higher than that of 3M group (P < 0.01), and BMP4 protein is mainly located in SCs and Leydig cells at different development stages. The CDS region of the Tibetan sheep BMP4 gene was 1,229 bp. CCK-8 results demonstrated that the proliferation rate of BMP4 was significantly increased in the overexpression group (pc-DNA-3.1(+)-BMP4; P < 0.05). In addition, the mRNA and protein expressions of SMAD5, BMPR1A, and BMPR1B and tight junction-related proteins Claudin11, Occludin, and ZO1 were significantly increased (P < 0.05). The mRNA expression of cell proliferation-related gene Bcl2 was significantly enhanced (P < 0.05), and the expression of GDNF was enhanced (P > 0.05). The mRNA expression of apoptosis-related genes Caspase3 and Bax decreased significantly (P < 0.05), while the mRNA expression of cell cycle-related genes CyclinA2 and CDK2 increased significantly (P < 0.05). It is worth noting that the opposite results were observed after transfection with si-BMP4. In summary, what should be clear from the results reported here is that BMP4 affects testicular development by regulating the Sertoli cells and BTB, thereby modulating the spermatogenesis of Tibetan sheep.

Dataset Information

Downregulation of Sostdc1 in Testicular Sertoli Cells is Prerequisite for Onset of Robust Spermatogenesis at Puberty.

Publications

Downregulation of Sostdc1 in Testicular Sertoli Cells is Prerequisite for Onset of Robust Spermatogenesis at Puberty.

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