The proteolytic activity of pregnancy-associated plasma protein-A is potentially regulated by stanniocalcin-1 and -2 during human ovarian follicle development

Jepsen, Malene R.; Kløverpris, Søren; Bøtkjær, Jane Alrø; Wissing, Marie Louise Muff; Andersen, Claus Yding; Oxvig, Claus

doi:10.1093/humrep/dew013

Cited by 43 publications

(53 citation statements)

References 58 publications

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“…STC2 is highly expressed in GCs to modulate the angiogenic or steroidogentic pathways or principal processes in ovarian function . STCs play an important role during folliculogenesis; however, the regulator of STCs in the ovary has not been reported. Our results showed that low‐dose melatonin could downregulate STC expression.…”

Section: Discussionmentioning

confidence: 99%

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Liu

Yang

et al. 2019

Journal of Pineal Research

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The interaction of granulosa cells (GCs) with oocytes is important to regulate follicle development. The exogenous melatonin promoting the maturation of oocytes by GCs has been approved in pig, however, the transcriptome profile and the functions of the genes regulated by melatonin in GCs have not yet to be fully characterized. In this study, we found melatonin could stimulate the synthesis of estradiol in pig GCs. The RNA‐seq was used to explore the effects of melatonin on gene expression, a total of 89 differentially expressed genes (DEGs) were identified. Gene ontology analysis showed DEGs which associated with regulation of cell proliferation, cell cycle, and anti‐apoptosis were significantly enriched. The functions of two DEGs, NOTCH2 and FILIP1L, were studied in pig GCs. The results showed that NOTCH2 inhibited the synthesis of estradiol, but FILIP1L promoted the synthesis of estradiol. Furthermore, inhibiting NOTCH2 in granulosa cells cocultured with cumulus‐oocyte‐complexes had no obvious effect on the maturation of pig oocyte, but could upregulate the cleavage rate of oocyte. We proved that FILIP1L had no effect on the maturation and cleavage of pig oocytes. Our work deepens the understanding of melatonin's effects on GCs and oocyte. The DEGs we found will be beneficial to reveal mechanisms of melatonin acting on GCs and oocytes and design the pharmacological interventions.

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Section: Discussionmentioning

confidence: 99%

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Liu

Yang

et al. 2019

Journal of Pineal Research

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“…However, only a few studies have investigated the impacts of these proteins on reproductive system function. STC1 was found to act downstream of adenyl cyclases in suppressing progesterone biosynthesis in STC‐mediated PAPPA proteolytic inhibition within human FF (Jepsen et al., ). ADAMTS9 increased expression in human granulosa cells after hCG treatment (Rosewell et al., ), as well as in dominant follicle of rhesus macaques after ovulatory stimulus (Peluffo, Murphy, Baughman, Stouffer, & Hennebold, ).…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of follicle fluids after superstimulation in one‐month‐old lambs

Lin

Han

et al. 2017

Reprod Domestic Animals

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Follicular fluid (FF) accumulates in the antrum of the ovarian follicle. In addition, FF provides the microenvironment for oocyte development, oocyte maturation and competence, which are acquired during follicular development. Superstimulatory treatment of 1-month-old lambs can achieve synchronous development of numerous growing follicles. However, these growing follicles are unable to completely mature and ovulate. Furthermore, the oocytes exhibit lower competence compared with those of ewes. In this study, we utilized an isobaric tag for relative and absolute quantification (iTRAQ)-based proteomics analysis and compare protein composition between pre-pubertal and adult superstimulated follicle FF in sheep. In total, 243 differentially expressed proteins were identified, including 155 downregulated and 88 upregulated between lamb and ewe. Gene ontology (GO) and KEGG pathway analysis indicated that the differentially expressed proteins are involved in signal transduction, anatomical structure development, stress response, metabolic pathways, and the complement and coagulation cascades. Many of the proteins known to affect follicle development were observed in lower abundance in FF of lamb (e.g. ADAMTS9, CD14, CTNNB1, FST, GCLC, HSPG2, IGFBP2, IGFBP6, INHBA, PRL, PAPPA, POSTN, PRDX1, SERPINA1, SOD3, STC1, VEGFC, etc.). However, a higher abundance was observed for proteasome proteins. Inadequate amounts of these proteins in FF may be lead to the unique characteristics of follicular development in lamb. These differentially expressed proteins illuminate the age-dependent changes in protein expression in the follicle microenvironment.

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“…On contrary, human STC2 transgenic mice were 45% smaller than wildtype littermates (54). STC2's negative regulation of postnatal growth was demonstrated by its ability to interact with pregnancy-associated plasma protein-A (PAPP-A), potentially inhibiting its proteolytic activity toward insulin-like growth factor binding protein 4 (IGFBP4) and causing reduction in insulin-like growth factor (IGF) signaling (55,56). Recent genome-wide association studies identified rare height increasing alleles of STC2 with compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP4 resulting in higher bioavailability of IGF (57).…”

Section: Role In Animal Developmentmentioning

confidence: 99%

New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

Joshi

2020

Front. Endocrinol.

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Stanniocalcin, a glycosylated peptide hormone, first discovered in a bony fish has originally been shown to play critical role in calcium and phosphate homeostasis. Two paralogs of stanniocalcin (STC1 and STC2) identified in mammals are widely expressed in variety of tissues. This review provides historical perspective on the discovery of fish and mammalian stanniocalcin, describes molecular regulation of STC2 gene, catalogs distribution as well as expression of STC2 in tissues, and provides key structural information known till date regarding mammalian STC2. Additionally, this mini review summarizes pivotal functions of STC2 in calcium and phosphate regulation, cytoprotection, cell development, and angiogenesis. Finally, STC2's role as a novel marker for human cancers has also been outlined. Reviewing these studies will provide an opportunity to understand STC2's structure, biological functions as well as key molecular pathways involving STC2, which will help us design innovative therapeutic interventions using this novel hormone.

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The proteolytic activity of pregnancy-associated plasma protein-A is potentially regulated by stanniocalcin-1 and -2 during human ovarian follicle development

Abstract: This work was supported by grants from the Novo Nordisk Foundation, and the Danish Council for Independent Research. No competing interests declared.

Cited by 43 publications

References 58 publications

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Proteomic profiling of follicle fluids after superstimulation in one‐month‐old lambs

New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

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