Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study

Lasse Bøllehuus Hansen; Mette Lorenzen; Ursula Bentin-Ley; John Erik Nielsen; Hans Krog; Anders Hayden Berg; Bonnie Sofie Håkansson; Astrid Munk Pedersen; Thomas Høst; Anders Juul; Martin Blomberg Jensen

doi:10.1016/j.jsbmb.2019.04.002

Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study

Lasse Bøllehuus Hansen, Mette Lorenzen, Ursula Bentin-Ley, John Erik Nielsen, Hans Krog, Anders Hayden Berg, Bonnie Sofie Håkansson, Astrid Munk Pedersen, Thomas Høst, Anders Juul, Martin Blomberg Jensen

Department of Clinical Medicine

1 Citation (Scopus)

Abstract

Male fertility is routinely evaluated by semen analysis, although semen quality variables such as; sperm count, motility and morphology have low predictive value for spontaneous pregnancies and fertility treatment outcomes. Vitamin D has been suggested to be beneficial for male reproduction. The vitamin D receptor and the vitamin D inactivating enzyme CYP24A1 are co-expressed in high quality sperm. Presence of CYP24A1 at the annulus of human sperm can distinguish between sperm from healthy and infertile men with high specificity and is positively correlated with semen quality. The high expression level in the testis of FAM57B2, which is activated by 24,25OH2D3, indicates an uncharacterized biological role for CYP24A1 in male reproduction. Moreover, activated vitamin D has been shown to induce sperm motility and promote fertilization in vitro. Here, we prospectively investigated whether the fraction of CYP24A1 positive sperm was a better predictor of clinical pregnancy than semen analysis by including 240 fertility treatments (169 couples) from a single fertility centre in Denmark. ROC-curve based analysis showed that the percentage of sperm expressing CYP24A1 was a better predictor of successful pregnancy outcome after intrauterine inseminations (IUI) than both sperm concentration and motility (p < 0.05). Interestingly, samples with CYP24A1 staining >67% of the sperm increased the likelihood of achieving pregnancy 4-fold after IUI compared with samples having fewer sperm with detectable CYP24A1 (p < 0.05). Neither CYP24A1 nor any of the other assessed semen quality variables were predictive for the treatment outcome of the more invasive assisted reproductive techniques (IVF and ICSI). In conclusion, our results provide proof of principle for a CYP24A1-based sperm test to improve fertility outcome for infertile patients referred for IUI and supports a role for vitamin D metabolites during fertilization.

Original language	English
Article number	105353
Journal	The Journal of Steroid Biochemistry and Molecular Biology
Volume	191
Number of pages	9
ISSN	0960-0760
DOIs	https://doi.org/10.1016/j.jsbmb.2019.04.002
Publication status	Published - Jul 2019

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Bøllehuus Hansen, L., Lorenzen, M., Bentin-Ley, U., Nielsen, J. E., Krog, H., Berg, A. H., Håkansson, B. S., Pedersen, A. M., Høst, T., Juul, A., & Blomberg Jensen, M. (2019). Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study. The Journal of Steroid Biochemistry and Molecular Biology, 191, [105353]. https://doi.org/10.1016/j.jsbmb.2019.04.002

Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination : A prospective study. / Bøllehuus Hansen, Lasse; Lorenzen, Mette; Bentin-Ley, Ursula et al.

In: The Journal of Steroid Biochemistry and Molecular Biology, Vol. 191, 105353, 07.2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Bøllehuus Hansen, L, Lorenzen, M, Bentin-Ley, U, Nielsen, JE, Krog, H, Berg, AH, Håkansson, BS, Pedersen, AM, Høst, T, Juul, A & Blomberg Jensen, M 2019, 'Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study', The Journal of Steroid Biochemistry and Molecular Biology, vol. 191, 105353. https://doi.org/10.1016/j.jsbmb.2019.04.002

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title = "Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study",

abstract = "Male fertility is routinely evaluated by semen analysis, although semen quality variables such as; sperm count, motility and morphology have low predictive value for spontaneous pregnancies and fertility treatment outcomes. Vitamin D has been suggested to be beneficial for male reproduction. The vitamin D receptor and the vitamin D inactivating enzyme CYP24A1 are co-expressed in high quality sperm. Presence of CYP24A1 at the annulus of human sperm can distinguish between sperm from healthy and infertile men with high specificity and is positively correlated with semen quality. The high expression level in the testis of FAM57B2, which is activated by 24,25OH2D3, indicates an uncharacterized biological role for CYP24A1 in male reproduction. Moreover, activated vitamin D has been shown to induce sperm motility and promote fertilization in vitro. Here, we prospectively investigated whether the fraction of CYP24A1 positive sperm was a better predictor of clinical pregnancy than semen analysis by including 240 fertility treatments (169 couples) from a single fertility centre in Denmark. ROC-curve based analysis showed that the percentage of sperm expressing CYP24A1 was a better predictor of successful pregnancy outcome after intrauterine inseminations (IUI) than both sperm concentration and motility (p < 0.05). Interestingly, samples with CYP24A1 staining >67% of the sperm increased the likelihood of achieving pregnancy 4-fold after IUI compared with samples having fewer sperm with detectable CYP24A1 (p < 0.05). Neither CYP24A1 nor any of the other assessed semen quality variables were predictive for the treatment outcome of the more invasive assisted reproductive techniques (IVF and ICSI). In conclusion, our results provide proof of principle for a CYP24A1-based sperm test to improve fertility outcome for infertile patients referred for IUI and supports a role for vitamin D metabolites during fertilization.",

author = "{B{\o}llehuus Hansen}, Lasse and Mette Lorenzen and Ursula Bentin-Ley and Nielsen, {John Erik} and Hans Krog and Berg, {Anders Hayden} and H{\aa}kansson, {Bonnie Sofie} and Pedersen, {Astrid Munk} and Thomas H{\o}st and Anders Juul and {Blomberg Jensen}, Martin",

year = "2019",

month = jul,

doi = "10.1016/j.jsbmb.2019.04.002",

language = "English",

volume = "191",

journal = "Journal of Steroid Biochemistry and Molecular Biology",

issn = "0960-0760",

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T1 - Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination

T2 - A prospective study

AU - Bøllehuus Hansen, Lasse

AU - Lorenzen, Mette

AU - Bentin-Ley, Ursula

AU - Nielsen, John Erik

AU - Krog, Hans

AU - Berg, Anders Hayden

AU - Håkansson, Bonnie Sofie

AU - Pedersen, Astrid Munk

AU - Høst, Thomas

AU - Juul, Anders

AU - Blomberg Jensen, Martin

PY - 2019/7

Y1 - 2019/7

N2 - Male fertility is routinely evaluated by semen analysis, although semen quality variables such as; sperm count, motility and morphology have low predictive value for spontaneous pregnancies and fertility treatment outcomes. Vitamin D has been suggested to be beneficial for male reproduction. The vitamin D receptor and the vitamin D inactivating enzyme CYP24A1 are co-expressed in high quality sperm. Presence of CYP24A1 at the annulus of human sperm can distinguish between sperm from healthy and infertile men with high specificity and is positively correlated with semen quality. The high expression level in the testis of FAM57B2, which is activated by 24,25OH2D3, indicates an uncharacterized biological role for CYP24A1 in male reproduction. Moreover, activated vitamin D has been shown to induce sperm motility and promote fertilization in vitro. Here, we prospectively investigated whether the fraction of CYP24A1 positive sperm was a better predictor of clinical pregnancy than semen analysis by including 240 fertility treatments (169 couples) from a single fertility centre in Denmark. ROC-curve based analysis showed that the percentage of sperm expressing CYP24A1 was a better predictor of successful pregnancy outcome after intrauterine inseminations (IUI) than both sperm concentration and motility (p < 0.05). Interestingly, samples with CYP24A1 staining >67% of the sperm increased the likelihood of achieving pregnancy 4-fold after IUI compared with samples having fewer sperm with detectable CYP24A1 (p < 0.05). Neither CYP24A1 nor any of the other assessed semen quality variables were predictive for the treatment outcome of the more invasive assisted reproductive techniques (IVF and ICSI). In conclusion, our results provide proof of principle for a CYP24A1-based sperm test to improve fertility outcome for infertile patients referred for IUI and supports a role for vitamin D metabolites during fertilization.

AB - Male fertility is routinely evaluated by semen analysis, although semen quality variables such as; sperm count, motility and morphology have low predictive value for spontaneous pregnancies and fertility treatment outcomes. Vitamin D has been suggested to be beneficial for male reproduction. The vitamin D receptor and the vitamin D inactivating enzyme CYP24A1 are co-expressed in high quality sperm. Presence of CYP24A1 at the annulus of human sperm can distinguish between sperm from healthy and infertile men with high specificity and is positively correlated with semen quality. The high expression level in the testis of FAM57B2, which is activated by 24,25OH2D3, indicates an uncharacterized biological role for CYP24A1 in male reproduction. Moreover, activated vitamin D has been shown to induce sperm motility and promote fertilization in vitro. Here, we prospectively investigated whether the fraction of CYP24A1 positive sperm was a better predictor of clinical pregnancy than semen analysis by including 240 fertility treatments (169 couples) from a single fertility centre in Denmark. ROC-curve based analysis showed that the percentage of sperm expressing CYP24A1 was a better predictor of successful pregnancy outcome after intrauterine inseminations (IUI) than both sperm concentration and motility (p < 0.05). Interestingly, samples with CYP24A1 staining >67% of the sperm increased the likelihood of achieving pregnancy 4-fold after IUI compared with samples having fewer sperm with detectable CYP24A1 (p < 0.05). Neither CYP24A1 nor any of the other assessed semen quality variables were predictive for the treatment outcome of the more invasive assisted reproductive techniques (IVF and ICSI). In conclusion, our results provide proof of principle for a CYP24A1-based sperm test to improve fertility outcome for infertile patients referred for IUI and supports a role for vitamin D metabolites during fertilization.

U2 - 10.1016/j.jsbmb.2019.04.002

DO - 10.1016/j.jsbmb.2019.04.002

M3 - Journal article

C2 - 30965119

SN - 0960-0760

VL - 191

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

M1 - 105353

ER -

Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study

Abstract

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