Mol. Hum. Reprod. Advance Access published online on November 29, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam082
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Fine scale quantification of HCG beta gene transcription in human trophoblastic and non-malignant non-trophoblastic tissues
1Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia 2Department of Obstetrics and Gynecology, University of Tartu, Lossi 36, 51003 Tartu, Estonia 3Department of Molecular Biology, EMD Serono Research Institute, One Technology Place, Rockland, MA USA 02093 4Andrology Unit, Tartu University Hospital, Puusepa 1A, 50406, Tartu, Estonia 5Nova Vita Clinic, Centre for Infertility Treatment and Medical Genetics, Kaluri tee 5A, Viimsi vald, 74001 Harjumaa Estonia
* Correspondence: Prof. Maris Laan, Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu; Riia St. 23, 51010 Tartu, Estonia; telephone: +372-7375008; fax: +372-7-420286, maris{at}ebc.ee
HCG is produced by syncytiotrophoblast of placenta. It delays the apoptosis of corpus luteum and functions in implantation. Its possible role in male reproduction has been raised. HCG beta subunit is encoded by CGB, CGB5, CGB7 and CGB8 genes located at 19q13.3 in a common genome cluster with beta subunit non-coding CGB1 and CGB2. We conducted a sensitive quantification and comparison of CGB gene expression in human trophoblastic (blastocysts, n=6; normal/failed pregnancy, n=51) and non-malignant non-trophoblastic tissues (15 different tissue types, samples n=241). by real-time RT-PCR. We showed a wide transcriptional window of CGB genes in normal pregnancy, a significant reduction in recurrent miscarriages, and a high expression (especially CGB1/CGB2) in ectopic and molar pregnancies. Expression was several orders of magnitude lower in the non-placental tissues, with the highest CGB levels being seen in testis, prostate, thymus, skeletal muscle and lung samples. The contribution of CGB1/CGB2 to the summarized expression of six CGB genes was not proportional to their gene dosage: 1/1000 to 1/10000. An interesting exception was the testis exhibiting a much higher CGB1/CGB2 to total CGB mRNA ratio of
1/3, corresponding to gene dosage. In conclusion, the expressional profile of CGB genes, activated already in blastocyst stage, is associated with the status of pregnancy. The presence of CGB transcripts in testes, and in particular CGB1/CGB2 transcripts, may indicate a role in male reproductive tract.
Key Words: Chorionic gonadotropin beta genes/normal and failed pregnancy/trophoblastic and non-trophoblastic CGB expression/CGB in male reproduction
Declaration of authors' roles: KR, RKC and ML designed the study; KR, MP and AS coordinated for the recruitment the study material; KR, PH, LU and JJ contributed to the acquisition of the data; KR, ML, JJ and RKC analyzed and interpreted the data; KR and ML drafted the manuscript and PH, LU, JJ, MP, AS and RKC revised it critically for substantial intellectual content. All the authors have read and approved the submitted manuscript version.
Submitted on September 14, 2007; resubmitted on November 8, 2007; accepted on November 27, 2007.