Testicular chromosomal mosaicism and infertility.

A healthy young man with azoospermia and no other endocrinological abnormalties was shown to have chromosomal mosaicism with the cytogenetic errors found only in testicular tissue. Three clones of cells were identified in both meiosis I and meiosis II by cytogenetic analysis of direct testicular smears. Peripheral blood karyotypes and buccal smear preparations revealed no abnormalities. It is postulated that the gonadal cytogenetic defects account for this patient's azoospermia. In addition, it is hypothesized that this type of incomplete spermatogenesis nonetheless produces sufficiet feedback material ("inhibin") so that FSH levels are not affected.     

Testicular tumors in male pseudohermaphroditism

The data are summarized on the incidence and morphofunctional characteristics of gonadal tumors in different varieties of false male hermaphroditism, namely the testicular feminization syndrome (marked and unmarked forms), demonstrable masculinization and dysgenesis and compared with the disease clinical manifestations. The two syndromes--testicular feminization (marked form) and dysgenesis were found to be associated with a high risk of cancer development. In the first case there develop sertolioma-like tumors and in the second one, tumors similar to gonocytoma and dysgerminoma. These tumors became malignant in rare cases, they did not recur or metastasize. The treatment schedule for such patients has been developed. It includes the removal of the tumor-affected gonads and transfer of the tumor-free gonads into subcutaneous abdominal or scrotal areas and administration (during castration) of continuous substitution hormonotherapy according to the sex chosen.     

Pyospermia and male infertility

Pyospermia is found on the semen analysis of up to 23% of men who are being investigated for infertility. The presence of significant numbers of white blood cells in the semen is correlated with poorer sperm parameters and diminished fertility. It is not known if these changes in sperm function are due to the white blood cells or to an underlying problem that may cause both pyospermia and altered sperm function. It is often assumed that pyospermia is an indication of an underlying genitourinary infection. However, studies have not shown an association between bacteria growing in reproductive tract fluids (semen, urine and expressed prostatic secretions) and pyospermia. Despite this, treating these patients with different antibiotics regimens appears to reduce temporarily the white blood cell count in the semen and improve the fertility rates. Well-controlled studies are needed to determine the role of antibiotics in the treatment of this significant cause of male infertility.     

Growth hormone in male infertility

Growth hormone (GH) is expressed in a variety of tissues, including the testes, and has autocrine and paracrine functions as well. This, along with other factors, exerts autocrine and paracrine control over spermatogenesis. GH, used as an adjuvant therapy, induces spermatogenesis in non-responder patients with hypogonadotropic hypogonadism, who are not responding to gonadotropin or pulsatile luteinizing hormone (LH) therapy. GH has an important physiological role to play in spermatogenesis and male fertility.     

Chromosomal alterations and male infertility

Reduced male fertility can be caused by genetic factors affecting gamete formation or function; in particular, chromosome abnormalities are a possible cause of male subfertility as shown by their higher frequency in infertile men than in the general male population. Meiotic studies in a number of these males have shown spermatogenesis breakdown, often related to alterations in the process of chromosome synapsis. Indeed, any condition that can interfere with X-Y bivalent formation and X-chromosome inactivation is critical to the meiotic process; furthermore, asynapsed regions may themselves represent a signal for the meiotic checkpoint that eliminates spermatocytes with synaptic errors. We performed cytogenetic, hormonal and seminal studies in 333 infertile patients selected because azoospermic, severely oligozoospermic or normozoospermic with failure to fertilize the partner's oocytes in an in vitro fertilization (IVF) program. Our findings: 1) confirm the high incidence of chromosomal anomalies among infertile males; 2) highlight the relevance in male infertility of quantitative/positional modifications of the constitutive heterochromatin; and 3) underline the relevance of cooperation between andrologists and cytogenetists prior to every kind of assisted reproduction, above all prior to intracytoplasmic sperm injection, in which selective hurdles eliminating abnormal germ cells are bypassed.     

Cancer and male infertility.

An increasing proportion of boys and young men with cancer will survive their disease and desire fertility. Unfortunately, the cancer treatment, and in some cases the malignant disease itself, may have a negative and permanent impact on the individual's fertility potential. This effect is highly dependent on the type and dose of therapy as well as the age at which it has been given. Basic knowledge in this field is necessary to enable oncologists and fertility specialists to counsel these patients about their fertility prospects and, if appropriate, advise them to take precautions (e.g. the cryopreservation of semen) to safeguard their fertility. Another aspect of the relationship between cancer and infertility is the possibility that men with testicular dysfunction may have an increased risk of testicular cancer. Screening for early testicular malignancy may therefore be advisable in some groups of men with poor semen quality.     

瘦素与男性不育症的关系

瘦素是由肥胖基因编码的一种蛋白质产物,属于Ⅰ型细胞因子,瘦素受体广泛分布于下丘脑、脂肪、睾丸、胎盘等组织,具有不同的生物功能.瘦素需与靶细胞膜上的瘦素受体结合,并通过多种信号转导途径才能发挥多种生物学效应.瘦素缺乏及瘦素受体的异常均可使生殖器官形态异常和导致与生殖相关的性激素分泌异常,进而引起男性不育症.目前研究发现,瘦素水平升高与精索静脉曲张、慢性前列腺炎、肥胖引起的男性不育,以及免疫相关性不育有关.     

Testicular growth and hormonal parameters in the male Snell dwarf mouse

Dwarf mice show delayed testicular growth and their adult testis weights are half the normal value. The aims of the present work were firstly, to compare the developmental profiles of plasma gonadotropins and of testicular cell multiplication and differentiation in dwarf vs normal mice and secondly, to determine the effect of hMG supplementation on dwarf mice. In the dwarf mice no pubertal rise in plasma FSH was observed, and the adult values remained very low when compared with those of normal mice; plasma LH decreased after 40 days of age and remained equal to half the normal values. In adults, testicular testosterone content was greatly increased in dwarf mice compared with normal mice, whereas plasma testosterone and accessory gland weights were reduced. At 24 days of age, the total numbers per testis of Leydig and Sertoli cells were reduced in dwarf vs normal mice, whereas in adult mice their differentiation, but not their total numbers, was reduced. This resulted in lower daily production of leptotene primary spermatocytes and of round spermatids in dwarf than in normal mice. hMG supplementation promoted Leydig and Sertoli cell multiplication, but did not produce full differentiation, resulting in increased daily production of round spermatids. In conclusion, in adult dwarf mice a deficiency in plasma gonadotropins prevents full differentiation of Leydig and Sertoli cells without affecting the number of these cells.     

Testicular function and fertility preservation in male cancer patients

The testis has been shown to be highly susceptible to the toxic effects of cancer therapy at all stages of life. Young cancer survivors are approximately half as likely as their siblings to sire a pregnancy. Radiation therapy to the testes and high cumulative dose of alkylating agents are the major factors decreasing the probability of fertility. This review aims to present an overview of the current state of knowledge in mechanisms how human spermatogonia proliferate and differentiate and how cancer therapy affects germ cells, what are the options for fertility preservation and what are the clinical risks and limitations related to such procedures. This area of research is discussed in the context of the potential future options that may become available for preserving fertility in male cancer patients.     

Contemporary concepts in the evaluation and management of male infertility

Infertility in men is a common condition. At the core of the medical evaluation of the male partner in a couple who are unable to conceive is the history and physical examination. Special attention should be directed to the patient's developmental history and any use of testosterone products. The physical examination focuses on the genitals, and includes assessments of the size and consistency of the testicles, epididymis, vas deferens, and presence of varicoceles. Although many sophisticated tests are available, semen analysis is still the most important diagnostic tool used to assess fertility, and includes parameters such as sperm count, motility and viability. Treatment of male factor infertility can involve targeted agents, in the case of specific conditions such as hypogonadotropic hypogonadism, or it can be empirical-using medical therapy or assisted conception techniques-for patients in whom no underlying cause has been identified. Although an all-encompassing treatment for male factor infertility has not yet been developed, the field offers many promising avenues of research.     

精子顶体酶活性与男性不育的研究进展

男性不育症发病率逐年增加,而临床上对于男性生育能力的评估仍然主要依赖精液常规检测,已不能满足现今临床的要求,一些新的检测指标开始被发现并发挥着重要的作用。精子顶体酶活性作为评价男性生育能力指标,已在临床应用多年,一直是男性不育的研究热点。该文就精子顶体酶活性的功能作用、影响因素、药物治疗及其与辅助生殖的研究进展作一综述,为男性不育的诊断与治疗提供新思路。     

Serum FSH and testicular morphology in male infertility

OBJECTIVE In patients with azoospermia serum FSH helps to differentiate between obstruction or spermatogenetic dysfunction as the possible cause of this condition. The role of FSH in the diagnosis of infertile men with oligoasthenoteratozoospermia is less clearly defined. In order to evaluate the diagnostic significance of serum FSH in the management of male infertility, serum FSH levels were related to testicular morphology from bilateral biopsies of infertile men. DESIGN AND PATIENTS Testicular biopsies were obtained from 213 infertile men and evaluated in semi-thin sections. Biopsies were performed either in order to distinguish between obstructive and non-obstructive azoospermia or because of subnormal semen variables when history, clinical investigation and hormone levels failed to explain infertility. Serum FSH was measured by fluoroimmunoassay. RESULTS Patients were divided into five groups on the basis of morphological criteria. The mean serum FSH value of patients with obstructive azoospermia and normal histology (group 1, n= 14) was normal (3.0 (2.2–4.1) IU/I) (mean (95% confidence limits)). Serum levels of FSH in non-obstructive oligo or azoospermia were as follows: group 2: mixed atrophy of tubular tissue without focal Sertoli cell only syndrome (SCO) (n= 104) (4.5 (4.0–5.1) IU/I), group 3: mixed atrophy with unilateral focal Sertoli cell only (n= 39) (7.4 (6.1–90) IU/I), group 4: mixed atrophy with bilateral focal SCO (n= 36) (107 (8.7–13.0) IU/I). Group 5: bilateral or unilateral total Sertoli cell only (n= 20) (16 0 (12 1–20 9) IU/I). Mean serum FSH levels were significantly different between all groups (P<0.05). CONCLUSIONS Elevation of serum FSH correlates with the appearance of Sertoli cell only tubules. Elevated FSH serum levels make testicular biopsies superfluous for diagnostic purposes, but normal FSH does not exclude severe derangement of spermatogenesis in individual cases.     

Androgen receptor polymorphisms and mutations in male infertility

Normal spermatogenesis depends on a sequential cascade of genetic events triggered by factors encoded by sex chromosomes. To determine the contribution of genetic aberrations to male infertility, the X-linked androgen receptor (AR) gene was examined for mutations and polymorphisms in a large cohort of infertile men. Genetic screening of over 400 patients and controls showed that defects in the AR gene lead to the production of dysfunctional receptor protein in up to 10% of males with abnormally low sperm production and male infertility. The dozens of mutations and polymorphisms uncovered were associated with subtly reduced intrinsic AR activity, and are of two main categories: polymorphic changes in length of a trinucleotide CAG tract in the N-terminal transactivation domain, and missense mutations in the C-terminal ligand-binding domain. These polymorphisms and mutations are associated with reduced AR function due to defective intermolecular protein-protein interactions with coactivator molecules. Genetic screening for AR mutations and polymorphism should be offered to severely oligospermic and azoospermic patients. These traits can be transmitted to progeny, and counseling can be offered to affected families. Clarification of the molecular mechanisms of pathogenesis has led to rational hormonal therapy.     

Medical and surgical management male infertility.

Male infertility is the result of a variety of highly treatable conditions. The critical step in treating male infertility is to evaluate properly every male partner of an infertile couple and to generate the proper treatment strategy. There are many medical and surgical options that can help most couples overcome male factor infertility. Male infertility can most easily be broken down into problems of sperm production (testicular dysfunction) and problems of sperm transport (obstruction). When applicable, medical therapies are used as an initial strategy to improve sperm production or as a preliminary therapy to boost production transiently in anticipation of a surgical sperm retrieval attempt. A range of surgical options is available to correct varicoceles, reconstruct the obstructed system, or retrieve sperm for assisted reproduction.     

Mesalazine-induced reversible infertility in a young male

Mesalazine is a well-established treatment for ulcerative colitis. A young man treated with mesalazine for proctitis was found to have pathological semen with a count of only 3 x 10(6) sperm cells/ml. He failed to achieve conception with his wife. When mesalazine treatment was stopped, semen analysis returned to near normal and pregnancy ensued. Due to recurrent disease activity, mesalazine treatment was reinstituted. This was followed by deterioration of the patient's semen.     

Environment, lifestyle and male infertility.

Our understanding of the importance of environmental and lifestyle factors on sperm count and fertility is constrained by the extreme variation in sperm count between men and between ejaculates. The factors responsible for this variation provide a key to understanding what factors actually affect the sperm count. The relative importance of the various factors and the pathways via which they affect sperm count are discussed. The most important are Sertoli cell number, ejaculatory frequency, season, factors affecting scrotal heating (e.g. the time spent seated), a past history of reproductive tract disorders and ageing. The possible role of other environmental factors commonly supposed to affect sperm count (exposure to pesticides or endocrine disruptors) is discussed, although the evidence for a major influence of such factors is lacking. It is suggested that lifestyle changes, especially in the time spent seated, will exert an adverse effect on sperm production in a progressively larger group of men over the next decade.