Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia

Passos, M. J.; Vasconcelos, G. L. de; Silva, A.W.B.; Brito, I.R.; Saraiva, M.V.A.; Magalhães, D. M.; Costa, Jonathan L.; Donato, Mariana Aragão Matos; Ribeiro, R.P.; Cunha, E.V.; Peixoto, Christina A.; Campello, C.C.; Figueiredo, J.R.; Hurk, R. van den; Silva, J.R.V.

doi:10.1016/j.theriogenology.2013.02.023

Cited by 21 publications

(13 citation statements)

References 37 publications

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“…In the current study, the inhibition of Gdf9 expression was only substantial in follicles >130 μm, at the time when Fshr expression is significantly upregulated. FSH-induced downregulation of Fshr is, however, a well-recognized phenomenon (38, 39). …”

Section: Discussionmentioning

confidence: 99%

Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture

et al. 2016

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The obligatory role of follicle-stimulating hormone (FSH) in normal development and function of ovarian antral follicles is well recognized, but its function in preantral growth is less clear. The specific objective of this study was to investigate the response, in culture, to FSH of mouse preantral follicles of increasing size, focusing particularly on growth rate and gene expression. Preantral follicles were mechanically isolated from ovaries of C57BL/6 mice, 12 to 16 days postpartum, and single follicles cultured for up to 96 hours in medium alone (n = 511) or with recombinant human FSH 10 ng/mL (n = 546). Data were grouped according to initial follicle diameter in 6 strata ranging from <100 to >140 μm. Follicles of all sizes grew in the absence of FSH (P < 0.01, paired t test). All follicles grew at a faster rate (P < 0.0001) in the presence of 10 ng/mL FSH but larger follicles showed the greatest change in response to FSH. Even the smallest follicles expressed FSH receptor messenger RNA (mRNA). FSH-induced growth was inhibited by KT5720, an inhibitor of protein kinase A (PKA), implicating the PKA pathway in FSH-induced follicle growth. In response to FSH in vitro, FSH receptor mRNA (measured by quantitative polymerase chain reaction) was reduced (P < 0.01), as was Amh (P < 0.01), whereas expression of StAR (P < 0.0001) and the steroidogenic enzymes Cyp11a1 (P < 0.01) and Cyp19 (P < 0.0001) was increased. These results show heterogeneous responses to FSH according to initial follicle size, smaller follicles being less FSH dependent than larger preantral follicles. These findings strongly suggest that FSH has a physiological role in preantral follicle growth and function.

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Section: Discussionmentioning

confidence: 99%

Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture

et al. 2016

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“…It is well known that the canonical BMP/Smad signaling pathway is associated with fecundity in domestic animals, and is essential for gonadogenesis, steroidogenesis, follicular development, and ovulation [8,10,38]. Meanwhile, BMP/Smad signaling pathway also plays an important role in follicular atresia, another fate of follicular development [39,40,41]. Follicular atresia is triggered by apoptosis of granulosa cells, therefore, most of its core components of the canonical BMP/Smad signaling pathway are related to the follicular granulosa cell functions, especially granulosa cell apoptosis in mammals [11,42].…”

Section: Discussionmentioning

confidence: 99%

Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells

Abdurahman

Yao

et al. 2019

IJMS

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BMPR1B is a type 1B receptor of the canonical bone morphogenetic protein (BMP)/Sma- and mad-related protein (Smad) signaling pathway and is well known as the first major gene associated with sheep prolificacy. However, little is known about the transcriptional regulation of the ovine BMPR1B gene. In this study, we identified the ovine BMPR1B gene promoter and demonstrated that its transcription was regulated by Smad4. In sheep ovarian follicles, three transcriptional variants of BMPR1B gene with distinct transcription start sites were identified using 5′ RACE assay while variants II and III were more strongly expressed. Luciferase assay showed that the region −405 to −200 nt is the PII promoter region of variant II. Interestingly, two putative Smad4-binding elements (SBEs) were detected in this region. Luciferase and ChIP assay revealed that Smad4 enhances PII promoter activity of the ovine BMPR1B gene by directly interacting with SBE1 motif. Furthermore, in the ovine granulosa cells, Smad4 regulated BMPRIB expression, and BMPRIB-mediated granulosa cells apoptosis. Overall, our findings not only characterized the 5’ regulatory region of the ovine BMPR1B gene, but also uncovered a feedback regulatory mechanism of the canonical BMP/Smad signaling pathway and provided an insight into the transcriptional regulation of BMPR1B gene and sheep prolificacy.

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“…Previous studies on sheep indicated that heterozygous mutations in BMP15 could increase the sensitivity of GCs in antral follicle to FSH stimulation, leading to increased ovulation rate(Fabre et al, 2006a). However, a recent study showed that treatment with BMP15 caused increased expression of Fshr in bovine preantral follicles after 12 days culturing(Passos et al, 2013). These conflicting reports probably caused by species-specific differences and the different response to BMP15 stimulation in each follicular development stages.…”

Section: Discussionmentioning

confidence: 99%

Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation

Qin

Tang

et al. 2019

Preprint

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13Bone morphogenetic protein 15 (BMP15) is a multifunctional oocyte-specific secreted factor. It controls 14 female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous 15 studies found that BMP15 played a critical role on follicular development and ovulation rate of 16 mono-ovulatory mammalian species, but has minimal impact on poly-ovulatory mice. However, whether this 17 is true in non-rodent poly-ovulatory species need to be validated. To investigate this question, we generated a 18 BMP15 knockdown pig model. We found that BMP15 knockdown gilts showed markedly reduced fertility 19 accompanied with phenotype of dysplastic ovaries containing significantly declined number of follicles, 20 increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered 21 ovulation. Molecular and transcriptome analysis revealed that knockdown of BMP15 significantly suppressed 22 cell proliferation, differentiation, Fshr expression, leading to premature luteinization and reduced estradiol 23 production in GCs, and simultaneously decreased the quality and meiotic maturation of oocyte. Our results 24 provide in vivo evidences for the essential role of BMP15 in porcine ovarian and follicular development, and 25 new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species. 26 KEY WORDS: BMP15; transgenic pig; follicular development; ovarian development 27 28 96cells (PEFs) derived from a male Yorkshire pig. Transfected PEFs then were subjected to G418 selection to 97 screen the cells with stable expression of EGFP as donor cells for somatic cell nuclear transfer (SCNT). Clone 98 embryos then were transferred into Large White sow recipients to generate F0 TG pigs as described in our 99 previous report (Liu et al., 2019) (Fig. S1A). We obtained two healthy F0 TG males at last. After sexual 100 maturity, one F0 TG boar was mated with wild-type sows to generate F1 TG gilts for subsequent experiments. 101Both F0 and F1 TG pigs showed visible intense GFP fluorescence on toes and muscle while subjected to 102 sunlight (Fig. 1C, Fig. S1B), directly suggesting that the pEGFP-BMP15 shRNA plasmid was successfully 103 integrated into the genome of F0 TG boar, and can be transmitted to the next generation through the germline. 104This was confirmed by PCR analysis of fragment of integrated plasmid in muscle tissue of F1 TG gilts ( Fig. 105 S2A). The copy number of integrated plasmid was estimated to be approximate seven in F1 TG pigs through 106 the combination of both qPCR that using a transferrin receptor gene to normalize the genomic DNA (data 107 not shown), and Southern blot analysis ( Fig. S2B). More importantly, evidently decrease level of BMP15 108 mRNA ( Fig. 1E) in 365 days old TG ovaries and BMP15 protein level in 30 days old TG ovaries ( Fig. 1F, G) 109 strongly demonstrated the successful generation of the BMP15 knockdown model, and implied an in vivo 110 BMP15 knockdown efficiency of about 50%...

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Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia

Cited by 21 publications

References 37 publications

Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture

Onset and Heterogeneity of Responsiveness to FSH in Mouse Preantral Follicles in Culture

Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells

Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation

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