Ultrastructurally Normal and Motile Spermatozoa in a Fertile Man with Kartagener's Syndrome

doi:10.1378/chest.102.5.1616

Chest

Volume 102, Issue 5, November 1992, Pages 1616-1618

https://doi.org/10.1378/chest.102.5.1616 Get rights and content

The findings in a 40-year-old man with Kartagener's triad (sinusitis, bronchiectasis, and situs inversus) and corrected transposition of the great vessels are presented. Electron microscopy revealed normal ultrastructure of the axoneme in both respiratory cilia and sperm tails. Light microscopic evaluation of the spermatozoa showed 50 percent motility, suggesting normal fertility. This assumption is confirmed, as the patient has two children. We suggest that an abnormal, uncoordinated motility pattern of the ultrastructurally normal respiratory cilia results in improper mucociliary clearance. This coordination is not needed in swimming spermatozoa, which could explain the apparent paradox between bronchopulmonary symptoms and normal fertility in our patient.

Section snippets

CASE REPORT

A 40-year-old man presented with a history of recent respiratory infection and progressive development of dyspnea, edema of the lower limbs, orthopnea, and palpitations. Throughout childhood, there had been a history of chronic cough, production of mucopurulent sputum, sinusitis, rhinorrhea, and conductive deafness. Situs inversus totalis had been diagnosed at birth, and as a child the patient had suffered from maxillary sinusitis and mastoiditis and successfully underwent surgery at the age of

DISCUSSION

Afzelius⁵ was the first to recognize that the relationship of Kartagener's triad with male infertility was due to immotility in both spermatozoa and respiratory cilia. Pedersen and Mygind⁶ suggested that this immotility was caused by an abnormal structure of the axonema, consisting of the absence of dynein arms. The protein, dynein, exhibits adenosine triphosphatase activity, necessary for ciliary motility, since it induces sliding of adjacent microtubule doublets.⁷ At that time a larger group

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Cited by (23)

Primary ciliary dyskinesia in adults
2016, Revue des Maladies Respiratoires
Citation Excerpt :
Plus rarement, il existe une azoospermie complète. Alors que les premières séries rapportaient une infertilité chez plus de 98 % des hommes, elle ne semble en fait présente que chez environ la moitié des hommes suivis pour DCP [35]. Le développement des études génétiques a permis de mettre en évidence l’existence de formes d’atteintes isolées de la lignée spermatique [36].
Primary ciliary dyskinesia is an autosomal recessive genetic disorder leading to structural and/or functional abnormalities of motor cilia. Impaired mucociliary clearance is responsible for the development of a multi-organ disease, which particularly affects the upper and lower airways.
In adults, primary ciliary dyskinesia is mainly characterized by bronchiectasis and chronic ear and sinus disorders. Situs inversus is found in half of patients and fertility disorders are commonly associated. Diagnosis is based on specialized tests: reduced level of nasal nitric oxide concentrations is suggestive of primary ciliary dyskinesia, but only a nasal or bronchial biopsy/brushing with analysis of beat pattern by videomicroscopy and/or analysis of cilia morphology by electronic microscopy can confirm the diagnosis. However, the diagnosis is difficult to achieve due to the limited access to these specialized tests and to difficulties in interpreting them. Genetic tests are under development and may provide new diagnostic tools. Treatment is symptomatic, based on airway clearance techniques (e.g., physiotherapy) and systemic and/or inhaled antibiotics. Prognosis is related to the severity of the respiratory impairment, which can be moderate or severe.
Diagnosis and management of primary ciliary dyskinesia remain poorly defined and should be supported by specialized centers to standardize the diagnosis, improve the treatment and promote research.
La dyskinésie ciliaire primitive est une maladie génétique autosomique récessive, à l’origine d’anomalies structurales et fonctionnelles des cils moteurs. Les altérations de la clairance mucociliaire sont responsables d’une atteinte multi-organes prédominant sur les voies aériennes supérieures et inférieures.
L’atteinte clinique est marquée chez l’adulte par des dilatations des bronches et une atteinte oto-sinusienne chronique. Un situs inversus est présent dans la moitié des cas et les troubles de la fertilité sont fréquents. Le diagnostic repose sur des tests spécialisés : un effondrement du monoxyde d’azote nasal est évocateur mais seuls un prélèvement de l’épithélium nasal ou bronchique pour une étude du battement ciliaire et une analyse en microscopie électronique permettent un diagnostic de certitude. Des tests génétiques sont en développement et pourraient favoriser le diagnostic dans les prochaines années. Le traitement est symptomatique, fondé sur la kinésithérapie respiratoire et l’antibiothérapie par voie systémique et/ou inhalée. Le pronostic est lié à l’atteinte respiratoire qui peut être modérée ou sévère.
La prise en charge de la dyskinésie ciliaire primitive reste mal codifiée et doit s’appuyer sur des centres spécialisés afin d’améliorer le diagnostic et les traitements, et de promouvoir la recherche.
Characterization of sperm DNA damage in Kartagener's syndrome with recurrent fertilization failure: Case revisited
2010, Sexual and Reproductive Healthcare
Single- and double-strand sperm DNA breaks was assessed in a Kartagener’s syndrome with four failures of fertilization after ISCI in TESA samples. It is concluded that in addition to failure of sperm motility, this patient was infertile because a high level of non-reparable sperm DNA damage was present. Although four cycles of insemination were performed at patient’s request, if the argument of an exacerbated level of sperm DNA damage could be used at the time of the medical advice, repeated failed cycles of insemination using ICSI could be avoided. Pregnancy was achieved with a semen donor.
Birth after intracytoplasmic sperm injection with use of testicular sperm from men with Kartagener or immotile cilia syndrome
2007, Fertility and Sterility
Citation Excerpt :
Kartagener’s syndrome is thus regarded as a subgroup of primary ciliary dyskinesia, which includes asynchronous ciliary beating, reduced or excessive motility, rotating or vibrating movement, or random ciliary orientation. All of these features could result in uncoordinated movement of respiratory cilia and contribute to impaired mucociliary clearance; however, this coordination is not needed in swimming spermatozoa (12). This could explain the paradoxical association between bronchopulmonary disease and normal fertility in some patients with Kartagener’s syndrome.
To describe a case of intracytoplasmic sperm injection (ICSI) with testicular sperm in men with immotile cilia syndrome and to discuss the role of micromanipulation in the treatment of these patients.
Case report.
Private infertility clinic and assisted reproduction unit.
Couple with male factor infertility due to Kartagener’s/immotile cilia syndrome.
The patient’s partner underwent ICSI with testicular sperm.
Semen characteristics, sperm viability, fertilization and cleavage rate, pregnancy, and birth after ICSI.
With testicular sperm, the two pronuclear fertilization rates were 53%. ICSI was successful in the first cycle. The uncomplicated pregnancy resulted in the birth of two healthy children, male/female twins.
With testicular sperm, successful oocyte fertilization after ICSI in couples with male Kartagener or immotile cilia syndrome is possible with nonprogressive motile sperm resulting in clinically healthy offsprings.
Kartagener's syndrome and infertility: Observation, diagnosis and treatment
2004, Journal de Gynecologie Obstetrique et Biologie de la Reproduction
Les dyskinésies ciliaires primitives sont des étiologies rares de stérilité primaire chez l’homme (prévalence de 1/6 000 à 1/40 000). Le syndrome de Kartagener est une entité particulière parmi ces dyskinésies ciliaires primitives. Il se transmet selon un mode autosomique récessif. Il se distingue par l’association d’un situs inversus, d’une polypose naso-sinusienne et d’une dilatation des bronches. Cette immobilité ciliaire est à l’origine de nombreuses infections broncho-pulmonaires, sinusiennes et chez l’homme d’infertilité. C’est à travers l’observation d’un couple dont l’homme est porteur de ce syndrome que sont évoquées les origines génétiques de cette dyskinésie et discutées les différentes prises en charge rapportées dans la littérature.
Primary ciliary dyskinesia is a rare etiology of sterility in man (prevalence between 1/6000 and 1/40000). Kartagener's syndrome is an autosomal recessive disorder, characterized by total or partial dysfunction of the ciliary or flagellated cells. This syndrome associates situs inversus, sinusitis, bronchiectasis and occasionally sterility in males. We report a case of immotile cilia syndrome with male infertility and compare the data with four other couples reported in the litterature (two couples in Germany, two in the United States). The difficulty is to select an alive sperm cell for ICSI.
Two molecular models of initial left-right asymmetry generation
1997, Medical Hypotheses
Left-right (LR) asymmetry is a fascinating problem in embryonic morphogenesis. Recently, a pathway of genes has been identified which is involved in LR patterning in vertebrates. Although this work characterizes the interactions of several asymmetrically-expressed genes, it is still entirely unclear how such asymmetric expression is set up in the first place. There are two promising molecular candidates which may play a role is such a process: the motor protein dynein, and the gap junction protein connexin-43 (C×43). We present two models, significantly supported by previous findings, which hypothesize that (a) dynein asymmetrically localizes LR determinants in individual cells to establish cell-autonomous LR biasing, and (b) asymmetric activity of C×43 gap junctions within key cells sets up electric potentials in multicellular fields, thus establishing large-scale LR asymmetry.
Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia
2009, Thorax
The diagnosis of primary ciliary dyskinesia (PCD) can be challenging, and it may be particularly difficult to distinguish primary ciliary disease from the secondary changes after infections.
The purpose of the study was to evaluate if nasal epithelial cells, obtained with nasal brushing instead of a biopsy, could be used in a culture system for the diagnosis of PCD in difficult cases.
Ciliary motion analysis (CMA) and transmission electron microscopy (TEM) were performed on 59 subjects with persistent or recurrent pneumonia. These investigations allowed the diagnosis of PCD in 13 (22%) patients while the defect of the cilia was considered secondary to infections in 37 (63%) subjects. In the remaining nine (15%) patients the diagnostic evaluation with CMA and TEM remained inconclusive. Ciliogenesis in culture allowed the diagnosis of PCD in four of these patients, it was indicative of a secondary defect in two subjects, and it was not helpful in the remaining three patients.
Culture of cells obtained with brushing of the nasal turbinate is not a perfect test, nevertheless it may offer diagnostic help in doubtful cases of PCD.

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Chest

Ultrastructurally Normal and Motile Spermatozoa in a Fertile Man with Kartagener's Syndrome

Section snippets

CASE REPORT

DISCUSSION

Lancet

Zur Pathogenese der Bronchiektasien: 1. Mitteilung: Bronchiektasien bei Situs viscerum inversus

Beitr Klin Tuberk

Kartageners syndrome and the syndrome of immotile cilia

Hum Genet

Evidence for congenitally nonfunctioning cilia in the tracheobronchial tract in two subjects

Am Rev Respir Dis

Male and female infertility problems in the immotile-cilia syndrome

Eur J Respir Dis

A human syndrome caused by immotile cilia

Science

Absence of axonemal arms in nasal mucosa cilia in Kartageners syndrome

Nature

What makes cilia and sperm tails beat?

N Engl J Med

The immotile-cilia syndrome: A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility

N Engl J Med

Immotile cilia syndrome in persons with and without Kartageners syndrome

Am Rev Respir Dis

Cilia with defective radial spokes: a cause of human respiratory disease

N Engl J Med