Bone Morphogenetic Proteins Are Mediators of Luteolysis in the Human Corpus Luteum

Nio‐Kobayashi, Junko; Trendell, Jennifer; Giakoumelou, Sevasti; Boswell, Lyndsey; Nicol, Linda; Kudo, Masataka; Sakuragi, Noriaki; Iwanaga, Toshihiko; Duncan, W. Colin

doi:10.1210/en.2014-1704

Cited by 42 publications

(36 citation statements)

References 39 publications

(53 reference statements)

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“…STAR and HSD3B1) involved in cholesterol transfer into mitochondria and conversion of pregnenolone to progesterone. These induced CLs were further characterised as having reduced expression of LHCGR (required for luteal support; Niswender et al 2007) and VEGFA (a key angiogenic regulator; Robinson et al 2007), together with increased expression of BMP2 (linked to luteolysis in regressing CLs; Nio-Kobayashi et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

et al. 2016

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Reproductive management in cattle requires the synchrony of follicle development and oestrus before insemination. However, ovulation of follicles that have not undergone normal physiological maturation can lead to suboptimal luteal function. Here, we investigated the expression of a targeted set of 47 genes in (a) a first-wave vs final-wave dominant follicle (DF; the latter destined to ovulate spontaneously) and (b) 6-day-old corpora lutea (CLs) following either spontaneous ovulation or induced ovulation of a first-wave DF to ascertain their functional significance for competent CL development. Both the mass and progesterone-synthesising capacity of a CL formed following induced ovulation of a first-wave DF were impaired. These impaired CLs had reduced expression of steroidogenic enzymes (e.g. STAR and HSD3B1), luteotrophic receptors (LHCGR) and angiogenic regulators (e.g. VEGFA) and increased expression of BMP2 (linked to luteolysis). Relative to final-wave DFs, characteristic features of first-wave

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Section: Discussionmentioning

confidence: 99%

Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

et al. 2016

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“…In concert with this study, a study using isolated human pre-antral follicles that compared the expression levels of BMPs in five size-matched populations demonstrated that BMP6 and BMP15 are the most abundantly expressed ligands (Kristensen et al ., 2014). In the human corpus luteum, BMP2, BMP4 and BMP6 are highly expressed in the granulosa-lutein and theca-lutein cells and are involved in the process of luteolysis (Nio-Kobayashi et al ., 2015). …”

Section: Intra-ovarian Bmps and Oocyte–somatic Cell Interactionsmentioning

confidence: 99%

“…(2013)BMP6Luteinized GCmRNA & ProteinRT-qPCR, IHCKhalaf et al . (2013)CLmRNA & ProteinRT-qPCR, IHCNio-Kobayashi et al . (2015)BMP7Luteinized GCmRNA & ProteinRT-qPCR, IHCKhalaf et al .…”

Section: Intra-ovarian Bmps and Oocyte–somatic Cell Interactionsmentioning

confidence: 99%

“…(2008)GCProteinIHCAbir et al . (2008)CLmRNA & ProteinRT-qPCR, IHCNio-Kobayashi et al . (2015)

BMR, bone morphogenetic proteins; GDF, growth differentiation factors; CL, corpora lutea; ELISA, enzyme-linked immunosorbent assay; FF, follicular fluid; IHC, immunohistochemistry; RT-qPCR, quantitative real-time PCR.

a Expressed only in fetal ovary.

…”

Section: Intra-ovarian Bmps and Oocyte–somatic Cell Interactionsmentioning

confidence: 99%

“…In contrast, a cohort study using GCs from normal healthy women and PCOS women showed that BMP7, but not BMP4, suppressed basal estradiol production, and both BMP4 and BMP7 had no effect on FSH-induced estradiol production in the normal women (Khalaf et al ., 2013). Studies using primary GCs obtained from IVF patients showed that BMP2, BMP4 and BMP6 suppressed StAR expression, whereas BMP2 induced aromatase expression (Shi et al ., 2011; Nio-Kobayashi et al ., 2015). Consistent with some of the previous studies, our recent results showed that BMP4, BMP7 and BMP15 all decreased progesterone production by down-regulating ALK3-mediated StAR expression in immortalized GCs (SVOG cells), but not in KGN cells (Chang et al ., 2013; Zhang et al ., 2015).…”

Section: Intra-ovarian Bmps and Oocyte–somatic Cell Interactionsmentioning

confidence: 99%

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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

222

207

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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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Effects of neonatal exposure to methoxychlor on corpus luteum in gilts: A transcriptomic analysis

Witek

Enguita

Grzesiak

et al. 2021

Molecular Reproduction Devel

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This study investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities, on luteal function in pigs. Piglets were injected subcutaneously with MXC (20 μg/kg body weight) or corn oil (control) between postnatal Days 1 and 10 (N = 5/group). Corpora lutea from sexually mature gilts were examined for luteal steroid and prostaglandin concentrations and processed for total RNA isolation and subsequent RNA sequencing. Intra‐luteal concentrations of androstenedione and prostaglandin E2 were greater, while that of estrone was lower when compared to control. Fifty‐three differentially expressed (DE) microRNAS (miRNAs) (p‐adjusted <.05 and log2(fold change) ≥.5) and 359 DE genes (p‐adjusted <.05 and log2(fold change) ≥1) were identified in luteal tissue in response to neonatal MXC treatment. MXC was found to affect the expression of genes related to lipogenesis, steroidogenesis, membrane transport, immune response, cell signaling and adhesion. These results suggest an earlier onset of structural luteolysis in pigs caused by MXC actions in neonates. Since negative correlation analysis showed the potential interactions of miRNAs with specific messenger RNAs, we propose that these miRNAs are potential mediators of the long‐term MXC effect on the CL function in pigs.

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Bone Morphogenetic Proteins Are Mediators of Luteolysis in the Human Corpus Luteum

Cited by 42 publications

References 39 publications

Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

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

Effects of neonatal exposure to methoxychlor on corpus luteum in gilts: A transcriptomic analysis

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