CRISP2 Is a Regulator of Multiple Aspects of Sperm Function and Male Fertility

Shuly Lim, Michelina Kierzek, Anne E. O'Connor, Christoph Brenker, D. Jo Merriner, Hidenobu Okuda, Marianna Volpert, Avinash Gaikwad, Deborah Bianco, David Potter, Ranganathan Prabhakar, Timo Strünker, Moira K. O'Bryan

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2 Citations (Scopus)

Abstract

The cysteine-rich secretory proteins (CRISPs) are a group of proteins that show a pronounced expression biased to the male reproductive tract. Although sperm encounter CRISPs at virtually all phases of sperm development and maturation, CRISP2 is the sole CRISP produced during spermatogenesis, wherein it is incorporated into the developing sperm head and tail. In this study we tested the necessity for CRISP2 in male fertility using Crisp2 loss-of-function mouse models. In doing so, we revealed a role for CRISP2 in establishing the ability of sperm to undergo the acrosome reaction and in establishing a normal flagellum waveform. Crisp2-deficient sperm possess a stiff midpiece and are thus unable to manifest the rapid form of progressive motility seen in wild type sperm. As a consequence, Crisp2-deficient males are subfertile. Furthermore, a yeast two-hybrid screen and immunoprecipitation studies reveal that CRISP2 can bind to the CATSPER1 subunit of the Catsper ion channel, which is necessary for normal sperm motility. Collectively, these data define CRISP2 as a determinant of male fertility and explain previous clinical associations between human CRISP2 expression and fertility.

Original languageEnglish
Pages (from-to)915-924
Number of pages10
JournalEndocrinology
Volume160
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

Cite this

Lim, Shuly ; Kierzek, Michelina ; O'Connor, Anne E. ; Brenker, Christoph ; Merriner, D. Jo ; Okuda, Hidenobu ; Volpert, Marianna ; Gaikwad, Avinash ; Bianco, Deborah ; Potter, David ; Prabhakar, Ranganathan ; Strünker, Timo ; O'Bryan, Moira K. / CRISP2 Is a Regulator of Multiple Aspects of Sperm Function and Male Fertility. In: Endocrinology. 2019 ; Vol. 160, No. 4. pp. 915-924.
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author = "Shuly Lim and Michelina Kierzek and O'Connor, {Anne E.} and Christoph Brenker and Merriner, {D. Jo} and Hidenobu Okuda and Marianna Volpert and Avinash Gaikwad and Deborah Bianco and David Potter and Ranganathan Prabhakar and Timo Str{\"u}nker and O'Bryan, {Moira K.}",
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Lim, S, Kierzek, M, O'Connor, AE, Brenker, C, Merriner, DJ, Okuda, H, Volpert, M, Gaikwad, A, Bianco, D, Potter, D, Prabhakar, R, Strünker, T & O'Bryan, MK 2019, 'CRISP2 Is a Regulator of Multiple Aspects of Sperm Function and Male Fertility', Endocrinology, vol. 160, no. 4, pp. 915-924. https://doi.org/10.1210/en.2018-01076

CRISP2 Is a Regulator of Multiple Aspects of Sperm Function and Male Fertility. / Lim, Shuly; Kierzek, Michelina; O'Connor, Anne E.; Brenker, Christoph; Merriner, D. Jo; Okuda, Hidenobu; Volpert, Marianna; Gaikwad, Avinash; Bianco, Deborah; Potter, David; Prabhakar, Ranganathan; Strünker, Timo; O'Bryan, Moira K.

In: Endocrinology, Vol. 160, No. 4, 01.04.2019, p. 915-924.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Okuda, Hidenobu

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AU - Gaikwad, Avinash

AU - Bianco, Deborah

AU - Potter, David

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AU - O'Bryan, Moira K.

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AB - The cysteine-rich secretory proteins (CRISPs) are a group of proteins that show a pronounced expression biased to the male reproductive tract. Although sperm encounter CRISPs at virtually all phases of sperm development and maturation, CRISP2 is the sole CRISP produced during spermatogenesis, wherein it is incorporated into the developing sperm head and tail. In this study we tested the necessity for CRISP2 in male fertility using Crisp2 loss-of-function mouse models. In doing so, we revealed a role for CRISP2 in establishing the ability of sperm to undergo the acrosome reaction and in establishing a normal flagellum waveform. Crisp2-deficient sperm possess a stiff midpiece and are thus unable to manifest the rapid form of progressive motility seen in wild type sperm. As a consequence, Crisp2-deficient males are subfertile. Furthermore, a yeast two-hybrid screen and immunoprecipitation studies reveal that CRISP2 can bind to the CATSPER1 subunit of the Catsper ion channel, which is necessary for normal sperm motility. Collectively, these data define CRISP2 as a determinant of male fertility and explain previous clinical associations between human CRISP2 expression and fertility.

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