Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells

Chang, Hsun‐Ming; Cheng, Jung‐Chien; Huang, He‐Feng; Shi, Fang; Leung, Peter C.K.

doi:10.1016/j.mce.2015.05.016

Cited by 47 publications

(24 citation statements)

References 44 publications

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“…This result might have been due to both a reduction in inhibin bioactivity and increased plasma activin concentrations following immunization against inhibin. The treatment of cultured marmoset luteal cells with antibodies to inhibin was found to decrease human chorionic gonadotropin (hCG)-induced progesterone secretion [40], whereas activin A has been shown to retard luteinization and inhibit progesterone production by luteinized granulosa cells [41][42][43][44]. It is obvious that immunization against inhibin compromises luteal development and functions and may exert a detrimental effect on conception, with reduced plasma progesterone concentrations.…”

Section: Discussionmentioning

confidence: 99%

Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Guo

Chen

Cheng³

et al. 2020

Animals

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This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.

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Section: Discussionmentioning

confidence: 99%

Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Guo

Chen

Cheng³

et al. 2020

Animals

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“…Indeed, inhibin βA ( Inhba ) and βB ( Inhbb ) subunit knockout mice exhibit different phenotypes, and the defects observed in Inhba knockout mice are only partially restored by insertion of Inhbb [ 27 , 28 ]. On the other hand, we have recently demonstrated that recombinant activin A, B and AB have similar effects on human ovarian granulosa cell steroidogenesis and placental trophoblast cell invasion [ 29 , 30 ]. Taken together, these studies suggest that activin A and B could function distinctly or similarly depending on the cellular context.…”

Section: Discussionmentioning

confidence: 99%

Activin B induces human endometrial cancer cell adhesion, migration and invasion by up-regulating integrin β3 via SMAD2/3 signaling

et al. 2015

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Endometrial cancer is the fourth most common female cancer and the most common gynecological malignancy. Although it comprises only ~10% of all endometrial cancers, the serous histological subtype accounts for ~40% of deaths due to its aggressive behavior and propensity to metastasize. Histopathological studies suggest that elevated expression of activin/inhibin βB subunit is associated with reduced survival in non-endometrioid endometrial cancers (type II, mostly serous). However, little is known about the specific roles and mechanisms of activin (βB dimer) in serous endometrial cancer growth and progression. In the present study, we examined the biological functions of activin B in type II endometrial cancer cell lines, HEC-1B and KLE. Our results demonstrate that treatment with activin B increases cell migration, invasion and adhesion to vitronectin, but does not affect cell viability. Moreover, we show that activin B treatment increases integrin β3 mRNA and protein levels via SMAD2/3-SMAD4 signaling. Importantly, siRNA knockdown studies revealed that integrin β3 is required for basal and activin B-induced cell migration, invasion and adhesion. Our results suggest that activin B-SMAD2/3-integrin β3 signaling could contribute to poor patient survival by promoting the invasion and/or metastasis of type II endometrial cancers.

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“…In line with these results, our previous studies showed that activins (activin A, B and AB) may act in a similar manner to modulate steroidogenesis in the same cell model (Chang et al ., 2015b). The downstream signaling pathway may account for the similar cellular effects, as both GDF8 and activins act through SMAD2/3-SMAD4-mediated target gene regulation in human GCs (Fang et al ., 2015; Chang et al ., 2015b). …”

Section: Novel Role Of Gdf8 In the Human Ovarymentioning

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

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226

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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...

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Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells

Cited by 47 publications

References 44 publications

Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Activin B induces human endometrial cancer cell adhesion, migration and invasion by up-regulating integrin β3 via SMAD2/3 signaling

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

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