Distruption of spermatogenesis: morphological aspects

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RUDN University

Distruption of spermatogenesis. Morphological aspects

N.G. Kulchenko

Abstract

At the beginning of the 21st century there is a decline in quality of reproductive health of men around the world. In structure of sterile marriage the men's factor of infertility is found out in approximately 40--50% of cases. A little studied question of male infertility is the question of quantity and quality of gametes in convoluted seminiferous tubules. Aim: to study morphological (quantitative and qualitative) changes of a seminiferous epithelium of patients with male infertility. Materials and Methods: 264 patients with male infertility have been examined. Patients with an obstructive form of infertility, with diseases sexually transmitted, with varicocele, with the revealed genetic and immunological factors of infertility have not been included in the research. Patients with a heavy form of pathospermia (n = 112) were taken a testis biopsy before the ICSI cycle (Intra Cytoplasmic Sperm Injection). Further a condition of the seminiferous epithelium of a testis was estimated with the use of light microscopy. Results: Hypoplasy of a seminiferous epithelium was revealed around 34 (30,5%) men, subtotal aplasia of a seminiferous epithelium -- around 59 (52,6%) patients, Sertoli Cell-only syndrome -- around 12 (10,7%) and tubular atrophy of convoluted seminiferous tubules -- around 7 (6,2% ) patients. Conclusions: The morphological research of testis gives the opportunity to define the extent of pathological process at all stages of a spermatogenesis. Only on the basis of studying of features of a spermatogenesis of the specific patient it is possible to make an algorithm of further personal medical and rehabilitation actions.

Key words: male infertility, spermatogenesis, assisted reproductive technologies, azoospermia, Sertoli Cell-only syndrome

Аннотация

НАРУШЕНИЕ СПЕРМАТОГЕНЕЗА. МОРФОЛОГИЧЕСКИЕ АСПЕКТЫ

Н.Г. Кульченко

Федеральное государственное автономное образовательное учреждение высшего образования «Российский университет дружбы народов», г. Москва, Россия

В начале 21 века во всем мире происходит снижение качества репродуктивного здоровья мужчин. В структуре бесплодного брака мужской фактор бесплодия встречается примерно в 40--50% случаев. Мало изученным остается вопрос при мужском бесплодии о количестве и качестве половых клеток в извитых семенных канальцах. Цель: изучить морфологические (количественные и качественные) изменения сперматогенного эпителия у пациентов с мужским бесплодием. Материалы и методы: были обследованы 264 пациента с мужским бесплодием. В исследование не включали пациентов с обструктивной формой бесплодия, с заболеваниями, передающимися половым путем, с варикоцеле, с выявленными генетическими и иммунологическими факторами бесплодия. Пациентам с тяжелой патоспермией (n = 112) перед циклом ICSI (Intra Cytoplasmic Sperm Injection) выполнялась биопсия яичка. Далее оценивали состояние сперматогенного эпителия яичка с помощью световой микроскопии. Результаты. У 34 (30,5%) мужчин выявлена гипоплазия сперматогенного эпителия, у 59 (52,6%) пациентов -- субтотальная аплазия сперматогенного эпителия, синдром «только клетки Сертоли» -- 12 (10,7%) и тубулярная атрофия извитых семенных канальцев -- 7 (6,2%). Выводы: Морфологическое исследование яичка дает возможность определить степень патологического процесса на всех стадиях сперматогенеза. Только на основании изучения особенностей сперматогенеза конкретного больного можно составить алгоритм дальнейших персональных лечебных и реабилитационных мероприятий.

Ключевые слова: мужское бесплодие, сперматогенез, вспомогательные репродуктивные технологии, азооспермия, синдром «Только клетки Сертоли»

Introduction

At the beginning of the 21st century there is a decline of quality of reproductive health of men around the world [1, 2]. Therefore male infertility is one of the main problems of Healthcare service worldwide [3, 4]. In structure of sterile marriage the men's factor of infertility is found ou in approximately 40--50% of cases [3, 5, 6]. Male infertility -- is a multifactorial disease [1, 5, 7, 8]. The variety of the factors leading to infertility make imply difficulties to the choice of necessary methods of diagnostics and treatment [9--11]. According to modern authors, about 30% of the men who have asked for medical care concerning infertility have oligozoo- spermia or azoospermia of an unknown etiology [11, 12]. These patients are the most difficult in termes of diagnostics and treatment of patospermia. The testis biopsy is shown to this category of patients with the diagnostic and medical purpose [13, 14].

The morphological research of testis offers the opportunity to define the degree of manifastation of pathological process at all stages of spermatogenesis, to estimate condition of blood supply and structure of the interstitial cells which characterize an endocrine function of testis [15--17].

The introduction of the assisted reproductive technologies (ART) in clinical practice allows men to become the genetic father of the child even with severe damage of spermatogenesis [3, 7, 18]. However, the question of quantity and quality of gametes in convoluted seminiferous tubules in case of male infertility remains a little studied.

Aim: to study morphological changes of a seminiferous epithelium of patients with male infertility.

Materials and methods

264 patients aged from 18 to 46 (34 ± 8) years with complaints to absence of pregnancy and spouse more than 12 months have been examined. The criteria of inclusion of men in a research was: age of 18 years, an established fact of infertility without contraception during more than 1 year, absence of pathology from the sexual partner. Patients with an obstructive form of infertility, with diseases sexually transmitted, with the varikocele, with the revealed genetic and immunological factors of infertility, with the heavy accompanying pathology at the time of inspection haven't been included in research. The protocol of the real research has been approved by the decision of ethical committee of medical institute of RUDN (No. 7 from 9/22/2016) and also corresponds to the Declaration of Helsinki (WMA Declaration of Helsinki -- Ethical Principles for Medical Research Involving Human Subjects, 64th WMA General Assambly, Fortaleza, Brazil, October 2013). The consent of patients to the research has been received.

The obligatory clinical trials of all patients were: medical history, general surveying, definition of a hormonal profile, double research of ejaculate (WHO, 2010).

All patients were taken a testis biopsy before the ICSI (Intra Cytoplasmic Sperm Injection). Tissue of testis was fixed in 10% neutral formalin which was filled in paraffin blocks later. Histological slices were painted with hematoxylin and eosin. We studied microscope slides with the use of light microscope at amplification of x400 (lens x40, ocular x10). During microscopy we estimated the cross-sectional area of the convoluted seminiferous tubules (CST), total quantity of spermatogenous cells and their subpopulation structure at the rate on one CST (on strictly crossed slices of CST).

We treated the obtained digital data on the computer with the use of Statistica v. 6.0 program, at the same time we carried out comparison of average values of indicators during the one-factorial dispersive analysis with the subsequent paired comparisons. Statistically significant were distinctions at p < 0,05.

Results and discussions

The majority of the examined patients was older than 30 years -- 71,2%. This fact can be explained with the developed tendency of a delayed registration of marriage and the birth of children because of aspiration of the man first of all to get an education and to promote that is regarded as “late paternity” today. Distribution of the examined patients according age is presented in table 1.

Table 1 / Таблица 1 Distribution of the examined patients according to the age / Распределение исследуемых пациентов по возрасту