Do alterations in follicular fluid proteases contribute to human infertility?

Cookingham, L.M.; Voorhis, Bradley J. Van; Ascoli, Mario

doi:10.1007/s10815-015-0447-9

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…ADAMTS-1 is induced in granulosa cells by LH during the periovulatory period and may be regulated by the progesterone receptor in the hormonal pathway leading to ovulation. A lack of ADAMTS-1 results in a decrease in female fertility and could influence human infertility [ 40 – 42 , 51 ]. Androgen Receptor (AR) plays an important role in male reproduction.…”

Section: Discussionmentioning

confidence: 99%

Identification of Copy Number Variations in Xiang and Kele Pigs

Xie

et al. 2016

PLoS ONE

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Xiang and Kele pigs are two well-known local Chinese pig breeds that possess rich genetic resources and have enormous economic and scientific value. We performed a comprehensive genomic analysis of the copy number variations (CNVs) in these breeds. CNVs are one of the most important forms of genomic variation and have profound effects on phenotypic variation. In this study, PorcineSNP60 genotyping data from 98 Xiang pigs and 22 Kele pigs were used to identify CNVs. In total, 172 candidate CNV regions (CNVRs) were identified, ranging from 3.19 kb to 8175.26 kb and covering 80.41 Mb of the pig genome. Approximately 56.40% (97/172) of the CNVRs overlapped with those identified in seven previous studies, and 43.60% (75/172) of the identified CNVRs were novel. Of the identified CNVRs, 82 (47 gain, 33 loss, and two gain-loss events that covered 4.58 Mb of the pig genome) were found only in a Xiang population with a large litter size. In contrast, 13 CNVRs (8 gain and 5 loss events) were unique to a Xiang population with small litter sizes, and 30 CNVRs (14 loss and 16 gain events) were unique to Kele pigs. The CNVRs span approximately 660 annotated Sus scrofa genes that are significantly enriched for specific biological functions, such as sensory perception, cognition, reproduction, ATP biosynthetic processes, and neurological processes. Many CNVR-associated genes, particularly the genes involved in reproductive traits, differed between the Xiang populations with large and small litter sizes, and these genes warrant further investigation due to their importance in determining the reproductive performance of Xiang pigs. Our results provide meaningful information about genomic variation, which may be useful in future assessments of the associations between CNVs and important phenotypes in Xiang and Kele pigs to ultimately help protect these rare breeds.

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Section: Discussionmentioning

confidence: 99%

Identification of Copy Number Variations in Xiang and Kele Pigs

Xie

et al. 2016

PLoS ONE

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“…This indicates that ADAMTS1 may not be a key protease, or other PGR regulated proteases contribute to the ovulatory mechanism. Lacking significant differences in gene expression, enzyme concentration, or enzymatic activity of ADAMTS1 in infertile women compared to controls also did not support functional roles of ADAMTS1 in human fertility [38]. ADAMTS1 has been suggested to cleave versican in COC matrix [37, 39], so the functions of this gene in basal vertebrates may be different since no COC is necessary.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Signatures for Ovulation in Vertebrates

Liu

Brewer

Chen

et al. 2016

Preprint

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14Recently, we found anovulation in nuclear progestin receptor (Pgr) knockout (Pgr-KO) zebrafish, 15 which offers a new model for examining Pgr regulated genes and pathways that are important for 16 ovulation and fertility. In this study, we examined expression of all transcripts using RNA-Seq in 17 pre-ovulatory follicular cells collected after the final oocyte maturation, but prior to ovulation, 18 from wild-type (WT) or Pgr-KO fish. Differential expression analysis revealed 2,888 genes 19 significantly differentially expressed between WT and Pgr-KO fish. Among those, 1,230 gene 20 transcripts were significantly more expressed, while 1,658 genes were significantly less expressed 21 in WT than those in Pgr-KO. We then retrieved and compared transcriptional data from online 22 databases and further identified 661 conserved genes in fish, mice, and humans, that showed 23 similar levels of high (283 genes) or low (387) expression in animals that were ovulating compared 24 to those with no ovulation. For the first time, ovulatory genes and their involved biological 25 processes and pathways were also visualized using Enrichment Map and Cytoscape. Intriguingly, 26 enrichment analysis indicated the genes with higher expression were involved in multiple 27 ovulatory pathways and processes such as inflammatory response, angiogenesis, cytokine 28 production, cell migration, chemotaxis, MAPK, focal adhesion, and cytoskeleton reorganization. 29In contrast, the genes with lower expression were mainly involved DNA replication, DNA repair, 30DNA methylation, RNA processing, telomere maintenance, spindle assembling, nuclear acid 31 transport, catabolic processes, nuclear and cell division. Our results indicate that a large set of 32 genes (>3,000) are differentially regulated in the follicular cells in zebrafish prior to ovulation, 33 terminating programs including growth and proliferation, and beginning processes including the 34 inflammatory response and apoptosis. Further studies are required to establish relationships among 35 these genes and an ovulatory circuit in zebrafish model. 37Ovulation is a physiological process that releases a fertilizable oocyte from follicular cells and is 38 an essential reproductive event for the preservation of a species. It is well established that 39 luteinizing hormone (LH) initiates a cascade of signaling; including upregulation of progestin and 40 its nuclear progestin receptor (PGR) which activates various downstream targets and signaling 41 pathways, eventually leading to follicular rupture. However, our understanding of the molecular 42 mechanisms that control ovulation is far from complete. For example, there is limited evidence of 43 downstream targets and signaling pathways that PGR regulates. A few genome-wide transcriptome 44 analyses of differentially expressed genes in the follicular cells of pre-ovulatory oocytes suggest 45 conserved gene expression regulation in humans, macaques, and mice [1-3]. To our knowledge, 46 there are no published transcriptomic analyses of gene e...

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“…Follicular fluid samples were obtained from eight patients undergoing in vitro fertilization (IVF) at the University of Iowa Hospitals and Clinics as previously described [23]. Patient material was obtained from women ≤ 38 years old, with male factor or tubal infertility.…”

Section: Methodsmentioning

confidence: 99%

Cytidine deaminase Apobec3a induction in fallopian epithelium after exposure to follicular fluid

Brachova

Alvarez

Voorhis

et al. 2017

Gynecologic Oncology

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Objective Ovarian carcinomas that originate from fallopian epithelial cells are suggested to arise due to repeated exposure to ovulatory follicular fluid (FF). Mechanistic explanation(s) for how this occurs are unknown. Here, we sought to understand if FF exposure to fallopian epithelial cells could induce DNA damage and expression of a known family of DNA mutators, apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) cytidine deaminases. Methods Follicular fluid and matched patient plasma samples were obtained from donors. Fallopian epithelial cells (FT33-TAg, FT189, FT190, and FT194) were cultured with FF or plasma for 24 hr, and cell proliferation and DNA damage were assessed. Effects of FF on Apobec gene expression was determined by qRT-PCR and western blot analyses. Fallopian epithelial cells were transfected with an APOBEC3A expression vector and DNA damage was assessed. Results Follicular fluid exposure increased epithelial cell proliferation as measured by three independent methods, and DNA damage accumulation as assessed using three independent measures. This effect was specific to FF, as matched patient plasma did not have the same effects. Increased expression of Apobec3a was observed in fallopian epithelial cells following exposure to 5 of 8 patient FF samples, and transient overexpression of APOBEC3A was sufficient to induce double strand DNA breaks. Conclusions Follicular fluid can induce cell proliferation and DNA damage accumulation in cultured fallopian epithelial cells. Increased expression of APOBEC3A, a known DNA mutator, may explain the high incidence of DNA damage after FF exposure. The role of Apobec3a in ovulation-induced inflammation warrants further investigation.

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Do alterations in follicular fluid proteases contribute to human infertility?

Cited by 4 publications

References 14 publications

Identification of Copy Number Variations in Xiang and Kele Pigs

Identification of Copy Number Variations in Xiang and Kele Pigs

Transcriptomic Signatures for Ovulation in Vertebrates

Cytidine deaminase Apobec3a induction in fallopian epithelium after exposure to follicular fluid

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