Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome

Wei, Li‐Na; Huang, Rui; Li, Li-Lin; Fang, Cong; Li, Yi; Liang, Xiaoyan

doi:10.1007/s10815-014-0319-8

Cited by 60 publications

(51 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As one of the oocyte secreted factors, GDF9 is crucial to follicular development. GDR9 plays an important role in follicular development, luteum formation, and embryo development [28,29]. RT-PCR results showed a significant (p<0.05) decrement of GDF9 mRNA on the effects of insulin (Fig.…”

Section: Ovarian Function Was Directly Impaired On the Effect Of Insulinmentioning

confidence: 88%

High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process

et al. 2017

Endocr J

View full text Add to dashboard Cite

METABOLIC DISORDERS, such as PCOS (polycystic ovary syndrome) and T2DM (type 2 diabetes mellitus), are reported to be associated with high miscarriage rates, decreased pregnancy rates, and low live birth rates [1]. PCOS and T2DM are characterized by hyperinsulinemia [2]. PCOS is an endocrine and metabolic disorder with a prevalence ranging from 5 to 13% in women of reproductive age. Moreover, PCOS is often accompanied by menstrual dysfunction, anovulaHigh insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process Abstract. Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2 diabetes mellitus), are associated with menstrual dysfunction, anovulation, infertility, and early pregnancy loss. Ovarian dysfunction is not only related to low pregnancy rates but also to the increased risk of miscarriage. Women with PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian dysfunction. In this study, we first explored whether high insulin levels directly affected ovarian functioning during embryo implantation. Mice in the insulin-treated group were given a subcutaneous injection of human recombinant insulin. After insulin treatment, serum levels of E2 (estrogen), PROG (progesterone), LH (luteinizing hormone), and FSH (follicle-stimulating hormone) were obviously lower, and there was a significant decrement of ovarian GDF9 (growth differentiation factor 9) mRNA. H&E (hematoxylin and eosin) staining showed a greater number of immature follicles and less luteinization in the insulin group. Further autophagy was studied in this process. A significant increase of P62 (SQSTM1/Sequestosome1) and a decrease of Cathepsin B, BECN1 (Beclin 1), and ULK1 (Unc-51-like kinase 1) mRNA in ovary was found in the insulin group. Western blot analysis showed that the expressions of LC3 (microtubule-associated protein 1 light chain 3), BECN1, and Cathepsin B proteins in ovaries from insulin group were obviously reduced, while P62 proteins were significantly increased. All these results illustrated that insulin could directly impair ovarian function during embryo implantation and the imbalance of ovarian autophagy due to insulin. Autophagy could enhance the impaired ovarian function results from insulin.

show abstract

Section: Ovarian Function Was Directly Impaired On the Effect Of Insulinmentioning

confidence: 88%

High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process

et al. 2017

Endocr J

View full text Add to dashboard Cite

show abstract

“…Using immunohistochemical staining, the expression levels of BMP15 and GDF9 proteins in the oocyte and GCs of follicles in PCOS ovaries are reduced and delayed during the early follicular stage (Wei et al ., 2014). Compared with the control group, the expression levels of BMP15 and GDF9 proteins in the oocytes tended to be higher in women with PCOS, which could be the result of PCOS follicular dysplasia (Zhao et al ., 2010).…”

Section: Role Of Bmps In Female Reproductive Pathologymentioning

confidence: 99%

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Chang

Qiao

Leung

2016

Hum. Reprod. Update

226

207

View full text Add to dashboard Cite

BACKGROUNDInitially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop.OBJECTIVE AND RATIONALEThe regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities.SEARCH METHODSRelevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016.OUTCOMESStudies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies have demonstrated the physiological role of intra-ovarian BMPs/GDFs in all aspects of ovarian functions, from follicle development to steroidogenesis, cell–cell communication, oocyte maturation, ovulation and luteal function. Furthermore, there is crosstalk between these potent ovarian regulators and the endocrine signaling system. Dysregulation or naturally occurring mutations within the BMP system may lead to several female reproductive diseases. The latest development of recombinant BMPs, synthetic BMP inhibitors, gene therapy and tools for BMP-ligand sequestration has made the BMP pathway a potential therapeutic target in certain human fertility disorders; however, further clinical trials are needed. Recent studies have indicated that GDF8 is an intra-ovarian factor that may play a novel role in regulating ovarian functions in the human ovary.WIDER IMPLICATIONSIntra-ovarian BMPs/GDFs are critical regulators of folliculogenesis and human ovarian functions. Any dysregulation or variations in these ligand...

show abstract

“…Reduced BMP15 and GDF9 expression was also reported in women with polycistic ovary syndrome (PCOS; Wei et al, 2014). Furthermore, a mutation in GDF9 was identified in young women with reduced ovarian reserve, being associated to reduced production of mature protein, decreasing GDF9 effect on human granulosa cells proliferation in vitro (Wang et al, 2013).…”

Section: Introductionmentioning

confidence: 97%

Expression of growth and differentiation Factor 9 and cognate receptors during final follicular growth in cattle

et al. 2016

View full text Add to dashboard Cite

Mutations in growth and differentiation factor 9 (GDF9) gene are associated to sterility or, paradoxically, increased ovulation rate in ewes. Despite its importance, the exact function of GDF9 in ovarian physiology is still poorly understood. This study aimed to investigate GDF9 function during dominant follicle growth and its regulation in follicular fluid. The regulation of GDF9 receptors in GnRH/LH-stimulated granulosa cells was also investigated. In a first experiment, a new follicular wave was induced and the intrafollicular GDF9 treatment into the largest growing follicle (8.5-9.5 mm) at both 100 (n = 3) and 1000ng/ml (n = 4) had no effect on follicular growth, estrus manifestation and ovulation compared to control (PBSinjected) follicles (n = 3). In a second experiment, follicles were obtained just after follicular deviation (day 4 after follicular emergence) and the abundance of GDF9 in follicular fluid did not differ between healthy dominant (n = 4) and atretic subordinate follicles (n = 4), as assessed by western blot analysis. Finally, mRNA expression of BMPR2 and TGFBR1 receptors was evaluated in granulosa cells obtained from preovulatory follicles (>12 mm diameter) obtained 0, 3, 6, 12 or 24 h after i.m. GnRH administration (n = 4-5 follicles/moment). Both receptors were significantly up regulated 12 h after GnRH treatment. Present results do not confirm the hypothesis that GDF9 inhibits dominant follicle growth and suggests a minor role in determining follicle fate. In the other hand, GDF9 receptors regulation in GnRH/LH-stimulated granulosa cells provides the first in vivo evidence of its involvement in the complex cascade of events that culminates in ovulation and luteinization in cattle.

show abstract

Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome

Cited by 60 publications

References 28 publications

High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process

High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Expression of growth and differentiation Factor 9 and cognate receptors during final follicular growth in cattle

Contact Info

Product

Resources

About