Top

Published in:

Open Access 01-12-2014 | Short communication

Mutant phenotype analysis suggests potential roles for C-type natriuretic peptide receptor (NPR-B) in male mouse fertility

Authors: Chizuru Sogawa, Yasuhiro Fujiwara, Satoshi Tsukamoto, Yuka Ishida, Yukie Yoshii, Takako Furukawa, Tetsuo Kunieda, Tsuneo Saga

Published in: Reproductive Biology and Endocrinology | Issue 1/2014

Abstract

Background

C-type natriuretic peptide (CNP) signaling through its receptor natriuretic peptide receptor B (NPR-B) is a key molecule for mammalian reproduction, and known to play important roles in female fertility. However, the function of these peptides in mouse male reproduction remains largely unknown. To determine the role of CNP/NPR-B signaling in male reproduction we investigated phenotype of Npr2-deficient short-limbed-dwarfism (Npr2^slw/slw) mice, which have been shown to have gastrointestinal (GI) abnormalities.

Findings

In homozygous Npr2^slw/slw mice, spermatogenesis is developmentally delayed at both 2 and 4 weeks of age, with vacuolation and degenerating apoptotic germ cells being observed at 3 weeks age. However, the adult Npr2^slw/slw mice exhibited apparently normal spermatogenesis, albeit with some aberrant spermatids, suggesting that developmental delay was overcome. In addition, the adult Npr2^slw/slw mice showed abnormal penile morphology (paraphimosis).

Conclusions

The potential role of CNP signaling via the NPR-B receptor in male fertility appears to be mediated not through germ-cell development, but may be through maintenance of normal penile function.

Available only for authorised users

Potter LR, Hunter T: Guanylyl cyclase-linked natriuretic peptide receptors: structure and regulation. J Biol Chem. 2001, 276: 6057-6060.CrossRefPubMed

Pyne NJ, Arshavsky V, Lochhead A: cGMP signal termination. Biochem Soc Trans. 1996, 24: 1019-1022.CrossRefPubMed

Komatsu Y, Itoh H, Suga S, Ogawa Y, Hama N, Kishimoto I, Nakagawa O, Igaki T, Doi K, Yoshimasa T, Nakao K: Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells. Role of the vascular natriuretic peptide system in vascular growth inhibition. Circ Res. 1996, 78: 606-614.CrossRefPubMed

Minamino N, Aburaya M, Kojima M, Miyamoto K, Kangawa K, Matsuo H: Distribution of C-type natriuretic peptide and its messenger RNA in rat central nervous system and peripheral tissue. Biochem Biophys Res Commun. 1993, 197: 326-335.CrossRefPubMed

Suga S, Nakao K, Itoh H, Komatsu Y, Ogawa Y, Hama N, Imura H: Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-beta. Possible existence of "vascular natriuretic peptide system". J Clin Invest. 1992, 90: 1145-1149.PubMedCentralCrossRefPubMed

Sogawa C, Wakizaka H, Aung W, Jin ZH, Tsuji AB, Furukawa T, Kunieda T, Saga T: C-type natriuretic peptide specifically acts on the pylorus and large intestine in mouse gastrointestinal tract. Am J Pathol. 2013, 182: 172-179.CrossRefPubMed

Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ: Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010, 330: 366-369.PubMedCentralCrossRefPubMed

Sogawa C, Tsuji T, Shinkai Y, Katayama K, Kunieda T: Short-limbed dwarfism: slw is a new allele of Npr2 causing chondrodysplasia. J Hered. 2007, 98: 575-580.CrossRefPubMed

Geister KA, Brinkmeier ML, Hsieh M, Faust SM, Karolyi IJ, Perosky JE, Kozloff KM, Conti M, Camper SA: A novel loss-of-function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia, Maroteaux type. Hum Mol Genet. 2013, 22: 345-357.CrossRefPubMed

10.

Tamura N, Doolittle LK, Hammer RE, Shelton JM, Richardson JA, Garbers DL: Critical roles of the guanylyl cyclase B receptor in endochondral ossification and development of female reproductive organs. Proc Natl Acad Sci U S A. 2004, 101: 17300-17305.PubMedCentralCrossRefPubMed

11.

Middendorff R, Davidoff MS, Behrends S, Mewe M, Miethens A, Muller D: Multiple roles of the messenger molecule cGMP in testicular function. Andrologia. 2000, 32: 55-59.PubMed

12.

Middendorff R, Muller D, Paust HJ, Holstein AF, Davidoff MS: New aspects of Leydig cell function. Adv Exp Med Biol. 1997, 424: 125-138.CrossRefPubMed

13.

Xia W, Mruk DD, Cheng CY: C-type natriuretic peptide regulates blood-testis barrier dynamics in adult rat testes. Proc Natl Acad Sci U S A. 2007, 104: 3841-3846.PubMedCentralCrossRefPubMed

14.

Sogawa C, Abe A, Tsuji T, Koizumi M, Saga T, Kunieda T: Gastrointestinal tract disorder in natriuretic peptide receptor B gene mutant mice. Am J Pathol. 2010, 177: 822-828.PubMedCentralCrossRefPubMed

15.

Horn MM, Ramos AR, Winkelmann L, Matte US, Goldani HA, Silveira TR: Seminiferous epithelium of rats with food restriction and carbon tetrachloride-induced cirrhosis. Int Braz J Urol. 2006, 32: 94-99. discussion 99CrossRefPubMed

16.

Wu A, Wan F, Sun X, Liu Y: Effects of dietary restriction on growth, neurobehavior, and reproduction in developing Kunmin mice. Toxicol Sci. 2002, 70: 238-244.CrossRefPubMed

17.

Kiyosu C, Tsuji T, Yamada K, Kajita S, Kunieda T: NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary. Reproduction. 2012, 144: 187-193.CrossRefPubMed

18.

Santos AM, Ferraz MR, Teixeira CV, Sampaio FJ, da Fonte Ramos C: Effects of undernutrition on serum and testicular testosterone levels and sexual function in adult rats. Horm Metab Res. 2004, 36: 27-33.CrossRefPubMed

19.

Zambrano E, Rodriguez-Gonzalez GL, Guzman C, Garcia-Becerra R, Boeck L, Diaz L, Menjivar M, Larrea F, Nathanielsz PW: A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development. J Physiol. 2005, 563: 275-284.PubMedCentralCrossRefPubMed

20.

Glossmann H, Petrischor G, Bartsch G: Molecular mechanisms of the effects of sildenafil (VIAGRA). Exp Gerontol. 1999, 34: 305-318.CrossRefPubMed

Title: Mutant phenotype analysis suggests potential roles for C-type natriuretic peptide receptor (NPR-B) in male mouse fertility
Authors: Chizuru Sogawa
Yasuhiro Fujiwara
Satoshi Tsukamoto
Yuka Ishida
Yukie Yoshii
Takako Furukawa
Tetsuo Kunieda
Tsuneo Saga
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2014
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/1477-7827-12-64

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mutant phenotype analysis suggests potential roles for C-type natriuretic peptide receptor (NPR-B) in male mouse fertility

Abstract

Background

Findings

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Findings

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

High-fat diet decreases the expression of Kiss1 mRNA and kisspeptin in the ovary, and increases ovulatory dysfunction in postpubertal female rats

Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review

Management of long-term and reversible hysteroscopic sterilization: a novel device with nickel-titanium shape memory alloy

The impact of mitochondrial function/dysfunction on IVF and new treatment possibilities for infertility

Making gametes from pluripotent stem cells – a promising role for very small embryonic-like stem cells

Polymorphisms in estrogen receptors predict the risk of male infertility: a meta-analysis