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The Hydroxysteroid ...
The Hydroxysteroid (17β) Dehydrogenase Family Gene HSD17B12 Is Involved in the Prostaglandin Synthesis Pathway, the Ovarian Function, and Regulation of Fertility.
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Kemiläinen, Heidi (författare)
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Adam, Marion (författare)
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Mäki-Jouppila, Jenni (författare)
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- Damdimopoulou, Pauliina (författare)
- Karolinska Institutet
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- Damdimopoulos, Anastasios E (författare)
- Karolinska Institutet
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- Kere, Juha (författare)
- Karolinska Institutet
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- Hovatta, Outi (författare)
- Karolinska Institutet
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Laajala, Teemu D (författare)
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Aittokallio, Tero (författare)
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Adamski, Jerzy (författare)
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- Ryberg, Henrik, 1971 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Strauss, Leena (författare)
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- Poutanen, Matti (författare)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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(creator_code:org_t)
- 2016-08-04
- 2016
- Engelska.
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:10, s. 3719-3730
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Abstract
Ämnesord
Stäng
- The hydroxysteroid (17beta) dehydrogenase (HSD17B)12 gene belongs to the hydroxysteroid (17β) dehydrogenase superfamily, and it has been implicated in the conversion of estrone to estradiol as well as in the synthesis of arachidonic acid (AA). AA is a precursor of prostaglandins, which are involved in the regulation of female reproduction, prompting us to study the role of HSD17B12 enzyme in the ovarian function. We found a broad expression of HSD17B12 enzyme in both human and mouse ovaries. The enzyme was localized in the theca interna, corpus luteum, granulosa cells, oocytes, and surface epithelium. Interestingly, haploinsufficiency of the HSD17B12 gene in female mice resulted in subfertility, indicating an important role for HSD17B12 enzyme in the ovarian function. In line with significantly increased length of the diestrous phase, the HSD17B(+/-) females gave birth less frequently than wild-type females, and the litter size of HSD17B12(+/-) females was significantly reduced. Interestingly, we observed meiotic spindle formation in immature follicles, suggesting defective meiotic arrest in HSD17B12(+/-) ovaries. The finding was further supported by transcriptome analysis showing differential expression of several genes related to the meiosis. In addition, polyovular follicles and oocytes trapped inside the corpus luteum were observed, indicating a failure in the oogenesis and ovulation, respectively. Intraovarian concentrations of steroid hormones were normal in HSD17B12(+/-) females, whereas the levels of AA and its metabolites (6-keto prostaglandin F1alpha, prostaglandin D2, prostaglandin E2, prostaglandin F2α, and thromboxane B2) were decreased. In conclusion, our study demonstrates that HSD17B12 enzyme plays an important role in female fertility through its role in AA metabolism.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (ämneskategori)
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Kemiläinen, Heid ...
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Adam, Marion
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Mäki-Jouppila, J ...
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Damdimopoulou, P ...
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Damdimopoulos, A ...
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Kere, Juha
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Hovatta, Outi
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Laajala, Teemu D
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Aittokallio, Ter ...
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Adamski, Jerzy
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Ryberg, Henrik, ...
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Ohlsson, Claes, ...
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Strauss, Leena
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Poutanen, Matti
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Endocrinology
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet