The regulation of the human corpus luteum steroidogenesis: a hypothesis?

Oon, V. J. H.; Johnson, M. R.

doi:10.1093/humupd/6.5.519

Cited by 18 publications

(10 citation statements)

References 38 publications

(55 reference statements)

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“…At the time of ovulation, a series of morphological transitions and tissue remodeling cause the ruptured ovarian follicle to develop into the corpus luteum, a temporary endocrine structure that secretes progesterone (Oon and Johnson, 2000). The release of progesterone targets and prepares the reproductive tract for initiation of fertilization and maintenance of early pregnancy (Niswender et al ., 2000).…”

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

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

223

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

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

223

207

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“…Since Wt1 is known to be expressed in the granulosa cells of primary follicles in the ovary (11,13), we asked whether folliculogenesis was affected. When quantifying the number of corpora lutea , the remnant of a follicle following ovulation which indicates oocyte maturation (14), we observed no difference between genotypes from E2.5 to E11.5 (Supplementary Material, Fig. S2B).…”

Section: Resultsmentioning

confidence: 94%

The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis

Nathan

Reinhardt

Kruspe

et al. 2017

Human Molecular Genetics

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Although the zinc finger transcription factor Wt1 has been linked to female fertility, its precise role in this process has not yet been understood. We have sequenced the WT1 exons in a panel of patients with idiopathic infertility and have identified a missense mutation in WT1 in one patient out of eight. This mutation leads to an amino acid change within the zinc finger domain and results in reduced DNA binding. We utilized Wt1+/- mice as a model to mechanistically pinpoint the consequences of reduced Wt1 levels for female fertility. Our results indicate that subfertility in Wt1+/- female mice is a maternal effect caused by the Wt1-dependent de-regulation of Prss29, encoding a serine protease. Notably, blocking Prss29 activity was sufficient to rescue subfertility in Wt1+/- mice indicating Prss29 as a critical factor in female fertility. Molecularly, Wt1 represses expression of Prss29. De-repression and precocious expression of Prss29 in the oviduct of Wt1+/- mice interferes with pre-implantation development. Our study reveals a novel role for Wt1 in early mammalian development and identifies proteases as critical mediators of the maternal-embryonic interaction. Our data also suggest that the role of Wt1 in regulating fertility is conserved in mammals.

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“…18 The rapid rise in serum hCG increases estrogen and progesterone levels, necessary for maintaining the corpus luteum and decidua basalis, until the placenta can support the pregnancy alone by approximately 7 weeks of gestation. 19 The vital importance of corpus luteum function was demonstrated in 1978, 20 when luteectomy prior to 7 weeks of gestation consistently resulted in miscarriage. Indeed, the abortifacient drug mifepristone, is a progesterone receptor antagonist.…”

Section: Luteal Insufficiencymentioning

confidence: 99%

“…24 At a molecular level hCG shares sequence homology with these cytokines, including vascular endothelial growth factor (VEGF). 19 In vitro, hCG can induce significant increases in VEGF levels. 23 A deficiency in either progesterone or hCG may therefore impact on the corpus luteum, preparation for implantation and endometrial support, resulting in miscarriage.…”

Section: Luteal Insufficiencymentioning

confidence: 99%

Preventing recurrent miscarriage of unknown aetiology

Morley

Shillito

Tang

2013

The Obstetric & Gynaecologis

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One to three per cent of couples are affected by recurrent miscarriage (defined as more than three consecutive pregnancy losses). Current interventions are centred on known causes of aetiology. Recent research on miscarriage of unknown cause has investigated the requirements for successful embryo implantation. Treatment of immunological risk factors with immunotherapy does not have a strong evidence base. The overall evidence supporting the use of human chorionic gonadotrophin supplementation during pregnancy is inconclusive. The efficacy of progesterone as an intervention remains empirical, with further trials under way. Learning objectivesTo understand the aetiology of recurrent miscarriage and patient risk factors.To understand the theoretical pathophysiology underlying miscarriage of unknown aetiology. To be aware of the potential agents of intervention for recurrent miscarriage and their efficacy. Ethical issuesTreating patients with recurrent miscarriage can be emotive; should women be treated with interventions that have limited evidence-based clinical efficacy? How do we manage patients with the psychological impact of recurrent miscarriage?

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The regulation of the human corpus luteum steroidogenesis: a hypothesis?

Cited by 18 publications

References 38 publications

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

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

The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis

Preventing recurrent miscarriage of unknown aetiology

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