Spermatogenesis In Men Research Articles

Vitamin D, Testosterone, and Thyroid Status in Young Men at Different Seasons

There are evidences that seasonal fluctuations in vitamin D levels coincide with annual rhythms of testosterone levels, and hypothyroidism may be a predictor of hypoandrogenism.
 The aim of the study was to establish the levels of vitamin D (vit. D), testosterone (T), thyroid stimulating hormone (TSH) and free thyroxine (T4f) in young people with pathospermia and normospermia in the spring-summer and autumn-winter periods.
 Materials and methods. The data of 58 men aged 23-44 years, who are in a sterile marriage, were analyzed: 24 were examined in the spring-summer period, 34 - in the autumn-winter period. BMI, levels of T, TSH, T4fandvit. Dwere investigated.
 Results. In the general group of men, the frequency of D - hypovitaminosis was higher in those examined in the autumn-winter period. Vit D levels were significantly lower with pathospermia than with normospermia. BMI did not significantly affect the level of vit.D in the blood.A direct correlation between vit. D and T in men with patho- and normospermiahas not been established, although such a correlation took place in the general group of the surveyed.
 The average TSH values ​​in the group examined in the spring-summer period did not significantly differ in the group with patho- and normospermia, and in those examined in the autumn-winter period, against the background of pathospermia, there was a decrease in T4f values ​​and an increase in TSH. 13.6% of this subgroup had laboratory signs of subclinical hypothyroidism.
 Conclusions:
 
 In men of the general group, without taking into account the state of the spermatogenic function of the testicles, examined in the autumn-winter period, there is a significant increase in the frequency of D-hypovitaminosis compared with a similar group of men in whom the level of vitamin D blood was determined in the spring-summer period.
 Regardless of the examination period, patients with pathospermia show a decrease in the average levels of vitamin D and testosterone compared to men with normal semen parameters.
 The frequency of vitamin D deficiency in patients with pathospermia significantly increases in the autumn-winter period.
 
 Disorders of spermatogenesis in men can be associated with the hypofunctional state of the thyroid gland against the background of the existing deficiency of vitamin D in the autumn-winter period.

Variant PNLDC1, Defective piRNA Processing, and Azoospermia

BackgroundP-element–induced wimpy testis (PIWI)–interacting RNAs (piRNAs) are short (21 to 35 nucleotides in length) and noncoding and are found almost exclusively in germ cells, where they regulate aberrant expression of transposable elements and postmeiotic gene expression. Critical to the processing of piRNAs is the protein poly(A)-specific RNase-like domain containing 1 (PNLDC1), which trims their 3′ ends and, when disrupted in mice, causes azoospermia and male infertility.MethodsWe performed exome sequencing on DNA samples from 924 men who had received a diagnosis of nonobstructive azoospermia. Testicular-biopsy samples were analyzed by means of histologic and immunohistochemical tests, in situ hybridization, reverse-transcriptase–quantitative-polymerase-chain-reaction assay, and small-RNA sequencing.ResultsFour unrelated men of Middle Eastern descent who had nonobstructive azoospermia were found to carry mutations in PNLDC1: the first patient had a biallelic stop–gain mutation, p.R452Ter (rs200629089; minor allele frequency, 0.00004); the second, a novel biallelic missense variant, p.P84S; the third, two compound heterozygous mutations consisting of p.M259T (rs141903829; minor allele frequency, 0.0007) and p.L35PfsTer3 (rs754159168; minor allele frequency, 0.00004); and the fourth, a novel biallelic canonical splice acceptor site variant, c.607-2A→T. Testicular histologic findings consistently showed error-prone meiosis and spermatogenic arrest with round spermatids of type Sa as the most advanced population of germ cells. Gene and protein expression of PNLDC1, as well as the piRNA-processing proteins PIWIL1, PIWIL4, MYBL1, and TDRKH, were greatly diminished in cells of the testes. Furthermore, the length distribution of piRNAs and the number of pachytene piRNAs was significantly altered in men carrying PNLDC1 mutations.ConclusionsOur results suggest a direct mechanistic effect of faulty piRNA processing on meiosis and spermatogenesis in men, ultimately leading to male infertility. (Funded by Innovation Fund Denmark and others.)

Вакцина Гам-КОВИД-Вак (Спутник V) не оказывает негативного влияния на сперматогенез у мужчин

Relevance. During the pandemic and large-scale vaccination against COVID-19, studies of the effect of various types of vaccines on human reproductive function have become particularly important. Vaccination may have a negative impact on the reproductive organs and tissues due to the development of an autoimmune process involving the gonads. Currently, there are some studies on the effect of vaccination against coronavirus infection caused by SARS-CoV2 on the male and female reproductive function. The absence of a negative effect of vaccination on spermatogenesis in men has already been demonstrated in the results of three studies. Objective. To evaluate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on spermatogenesis and the level of antiphospholipid antibodies in men. Materials and methods. The prospective study included 45 men who were vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V). The criteria for inclusion in the study were the age from 18 to 55 years, the absence of a previous history of COVID-19, a negative RT-PCR result in SARS-CoV-2 testing, negative SARS-CoV-2 IgG results prior to vaccination, and the absence of severe somatic diseases. The patients were examined twice: immediately before vaccination and 90 days after the first dose was injected. We evaluated spermogram parameters, determined the levels of FSH, LH, TSH and total testosterone, and analyzed blood for IgM and IgG antiphospholipid antibodies (aPL) to cardiolipin (aCL), β2-glycoprotein-1 (as2-GP1), annexin V (aAnV), phosphatidylserine (aPS), as well as IgG antibodies to SARS-CoV-2 using enzyme immunoassay. Results. There were no significant changes in the parameters of spermogram and hormone levels before and after vaccination;men with moderate impairment of spermatogenesis (oligoasteno-and/or teratozoospermia) did not show considerable changes either. The level of aPL after vaccination did not increase compared to the baseline level. Besides, there was no correlation between the dynamics of the level of antisperm antibodies, aPL and spermogram parameters. These findings indirectly indicate that there are no changes in the reproductive function associated with this autoimmune factor after vaccination in men. Conclusion. This is one of the first studies that has revealed the effect of the Gam-COVID-Vac vaccine on spermatogenesis, hormonal profile and aPL level in men. The obtained results demonstrate that the Gam-COVID-Vac vaccine does not have a negative effect on the reproductive function in men.

Identification and Relative Quantification of hFSH Glycoforms in Women's Sera via MS-PRM-Based Approach.

Follicle-stimulating hormone (FSH) is a glycohormone synthesized by adenohypophysis, and it stimulates ovulation in women and spermatogenesis in men by binding to its receptor (FSHR). FSHR is involved in several mechanisms to transduce intracellular signals in response to the FSH stimulus. Exogenous FSH is currently used in the clinic for ovarian hyperstimulation during in vitro fertilization in women, and for treatment of infertility caused by gonadotropin deficiency in men. The glycosylation of FSH strongly affects the binding affinity to its receptor, hence significantly influencing the biological activity of the hormone. Therefore, the accurate measurement and characterization of serum hFSH glycoforms will contribute to elucidating the complex mechanism of action by which different glycoforms elicit distinct biological activity. Nowadays ELISA is the official method with which to monitor serum hFSH, but the test is unable to distinguish between the different FSH glycovariants and is therefore unsuitable to study the biological activity of this hormone. This study presents a preliminary alternative strategy for identifying and quantifying serum hFSH glycoforms based on immunopurification assay and mass spectrometry (MS), and parallel reaction monitoring (PRM) analysis. In this study, we provide an MS–PRM data acquisition method for hFSH glycopeptides identification with high specificity and their quantification by extracting the chromatographic traces of selected fragments of glycopeptides. Once set up for all its features, the proposed method could be transferred to the clinic to improve fertility treatments and follow-ups in men and women.

Induction of spermatogenesis in men with hypogonadotropic hypogonadism

PurposeWe compared our clinical experience to international standards, assessed by response to treatment and pregnancy rates to ensure our results were comparable.MethodsMen presenting with azoospermia related to hypogonadism were recruited into a treatment programme which was managed by one person over 8 years in a secondary care facility. Treatment followed published management plans using urinary gonadotropins. Data were collected on success rates in spermatogenesis, as well as variables which might predict success, and costs. Statistical analysis used non-parametric methods.ResultsOf 16 men with HH, 14 achieved spermatogenesis, and 9 had sperm cryopreserved. Of those 14, 6 were successful in achieving a pregnancy with their partner from assisted conception (including ICSI) and one after natural conception. Factors identified to identify men likely to be successful in treatment were whether testicular volume was larger at onset of gonadotropins (median 10 mL) with a trend towards greater success if the cause developed after puberty. Mean treatment costs per man treated amounted to GP£4379/UD$5377 (figures for September 2020).SummarySuccess rates from this treatment should exceed 70% in most clinical settings. The likelihood of success improves when testicular volume exceeded 10 mL at initiation of treatment and a trend exists whereby success is more likely whereby when hypogonadism developed after puberty. Treatment costs are at a level likely to benefit quality of life, supporting the delivery of this treatment and where necessary and possible, funding it in line with other fertility treatments. This treatment should be available much more widely as a management option for men with hypogonadism, allowing them to father a biological child, rather than using donor sperm.

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms.

Metformin (MF), a first-line drug to treat type 2 diabetes mellitus (T2DM), alone and in combination with other drugs, restores the ovarian function in women with polycystic ovary syndrome (PCOS) and improves fetal development, pregnancy outcomes and offspring health in gestational diabetes mellitus (GDM) and T2DM. MF treatment is demonstrated to improve the efficiency of in vitro fertilization and is considered a supplementary drug in assisted reproductive technologies. MF administration shows positive effect on steroidogenesis and spermatogenesis in men with metabolic disorders, thus MF treatment indicates prospective use for improvement of male reproductive functions and fertility. MF lacks teratogenic effects and has positive health effect in newborns. The review is focused on use of MF therapy for restoration of female and male reproductive functions and improvement of pregnancy outcomes in metabolic and endocrine disorders. The mechanisms of MF action are discussed, including normalization of metabolic and hormonal status in PCOS, GDM, T2DM and metabolic syndrome and restoration of functional activity and hormonal regulation of the gonadal axis.

Circulating Zinc and Copper Levels are Associated with Sperm Quality in Obese Men after Metabolic Surgery: A Pilot Study.

(1) Background: Inadequate levels of several trace elements and vitamins may impair spermatogenesis in men. Although weight loss after metabolic surgery normalizes male reproductive hormones, sperm quality seems to not improve. We hypothesized that circulating concentrations of zinc, copper and other trace elements and vitamins might be involved. (2) Methods: We studied 20 men submitted to metabolic surgery at baseline and after two years. Hormone profiles, serum trace elements and vitamins were studied together with sperm analysis. (3) Results: At follow-up, serum testosterone, follicle-stimulating hormone and inhibin B concentrations increased showing a beneficial hormonal response for spermatogenesis. Conversely, serum copper, zinc and ferritin showed a decline after surgery. In total, 33% of men showed zinc deficiency, 27% copper deficiency and 20% iron deficiency, among others. Sperm analysis showed that all revaluated patients had at least one abnormal parameter. Serum zinc concentrations showed a positive correlation with progressive motility (r = 0.577, p = 0.031), and serum ferritin a positive correlation with sperm volume (ρ = 0.535, p = 0.049). Serum copper showed a weak and near significant correlation with motility (r = 0.115, p = 0.051). (4) Conclusions: The lack of improvement in sperm quality in obese men after metabolic surgery may be related to nutrient malabsorption, especially zinc, copper and iron.

Pregnancy and live birth rate in idiopathic male infertility treated with Human Menopausal Gonadotropin: A pilot clinical trial

Background & aim: Idiopathic male infertility refers to the condition in which there is no clear cause for the diagnosis of infertility. Human menopausal gonadotropin (HMG) containing the follicle-stimulating hormone and luteinizing hormone is a medication that causes ovarian follicles to grow in women. This medication can also induce spermatogenesis in men. The present study was conducted to investigate and compare the rates of pregnancy and live birth in partners of men with unexplained infertility after the injection of 8 and 12 ampules of HMG. Methods: This clinical trial study was carried out on 22 men with unexplained infertility who referred to the Urology Clinic of Rafsanjan University of Medical Sciences, Rafsanjan, Iran, during March 2016 and December 2018. The patients were randomly divided into two groups each of which included 11 cases. For one group 8 HMG injections and for the other group 12 HMG injections were administered (two injections per week). Afterward, the results of clinical pregnancy were assessed, and the cases were followed up to live birth after the clinical pregnancy. Data analysis was carried out using the Chi-square test. Results: In this study, the rate of positive pregnancy was reported as 62.5% in the group with 12 HMG injections in comparison to 37.5% in the group with 8 HMG injections. Although the pregnancy rate was higher in the 12-injection group, statistically there was no significant difference (P=0.7). Conclusion: According to the results of the present study, it can be concluded that for couples with unexplained male infertility, the administration of 8 to 12 HMG injections can increase the chance of pregnancy and live birth. Since this study was the first attempt to evaluate the pregnancy rate after treatment with HMG, it is suggested to perform further studies for the assessment of HMG effect on hormonal profile and chromatin quality.

Disruptions of spermatogenic function after testicle torsion in childhood and adolescence

Aim of research. To assess the state of spermatogenesis in men after an experience of testicle torsion in childhood and adolescence. 
 Materials and methods. A semen analysis was performed involving 76 men, ages 18 to 29 years, who had testicle torsion in childhood and adolescence. Inclusion criteria in this study were an age of 18 years and an active sexual life. Analysis of the ejaculate was performed in accordance with the World Health Organization Guidelines for the study of human ejaculate. Macroscopic and microscopic evaluation of ejaculate, as well as assessment of motility, viability, number, and morphology of sperm was performed. The control group included 49 men who lacked potential risk factors for male infertility. 
 Results and discussion. Changes in the ejaculate depended on the patient's age, as well as the duration and degree of testicular ischemia. When the gonad was preserved after critical ischemia occurred, the spermogram indices were significantly worse than when performing primary orchiectomy, which indicates functional failure of the gonad following its atrophy and suggests that it is inadvisable to maintain the gonad with the expectation of improved long-term results. 
 Conclusions: 1. Changes in the spermogram after ischemia were observed in terms of sperm morphology and mobility. 2. The most pronounced changes in the spermogram were noted in patients who had experienced third-degree inversion of the testicle with preservation of gonads; the least pronounced changes were noted in patients who had experience inversion with spontaneous generation and incomplete inversion, which involved minimal ischemic damage. 3. The worst ischemia in puberty occurred in the context of mature sex glands. 4. There was a direct dependence of spermogram changes on the duration of acute ischemia. 5. The most unfavorable combination occurred in puberty, with disease lasting for more than 1 day, comprising complete inversion with “critical” ischemia. 6. After critical ischemia with preservation of the gonad, the semen is less favorable than after completion of orchiectomy, due to the failure of atrophied gonads; this finding casts doubt on the practice of gonad preservation.

FSHR Trans-Activation and Oligomerization.

Follicle stimulating hormone (FSH) plays a key role in human reproduction through, among others, induction of spermatogenesis in men and production of estrogen in women. The function FSH is performed upon binding to its cognate receptor—follicle-stimulating hormone receptor (FSHR) expressed on the surface of target cells (granulosa and Sertoli cells). FSHR belongs to the family of G protein-coupled receptors (GPCRs), a family of receptors distinguished by the presence of various signaling pathway activation as well as formation of cross-talking aggregates. Until recently, it was claimed that the FSHR occurred naturally as a monomer, however, the crystal structure as well as experimental evidence have shown that FSHR both self-associates and forms heterodimers with the luteinizing hormone/chorionic gonadotropin receptor—LHCGR. The tremendous gain of knowledge is also visible on the subject of receptor activation. It was once thought that activation occurs only as a result of ligand binding to a particular receptor, however there is mounting evidence of trans-activation as well as biased signaling between GPCRs. Herein, we describe the mechanisms of aforementioned phenomena as well as briefly describe important experiments that contributed to their better understanding.

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone-oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone-oestradiol ratio? Prospective study of men with idiopathic severe oligozoospermia (sperm concentration <5 million/ml) carried out between February 2015 and March 2017. The objective was to assess if semen-analysis parameters improved after treatment with letrozole. Secondary objectives were to monitor the safety of letrozole in men, and to measure the alterations in serum FSH, LH, oestradiol and testosterone levels. Fifteen men with normal testosterone-oestradiol ratio (>10) were treated with letrozole 2.5 mg daily for 4 months. This produced a 5.5-fold increase in sperm concentration (P = 0.0068). All men had increased total serum testosterone and suppressed oestradiol levels after treatment, thus raising the overall testosterone-oestradiol ratio (P < 0.0001). Adverse effects from letrozole were relatively minor and included loss of libido (54%), headaches (25%), fatigue (21%), weakness (13%), loss of hair (8%) and dry mouth (8%). Letrozole improves sperm concentration and increases testosterone-oestradiol ratio for men with oligozoospermia who have normal testosterone-oestradiol ratio; its role in the treatment of male infertility may be extended to this group of patients. In addition, it is a relatively well-tolerated drug with no serious adverse effects.

Kisspeptin and Metabolism: The Brain and Beyond.

Apart from the well-established role of kisspeptin (Kp) in the regulation of reproductive functions, recent data described its action in the control of metabolism. Of particular interest for the review is the population of Kp neurons localized in the arcuate nucleus (ARC) of the hypothalamus, the site of the brain where reproductive and metabolic cross talk occurs. However, within the hypothalamus Kp does not work alone, but rather interacts with other neuropeptides, e.g., neurokinin B, dynorphin A, proopiomelanocortin, the cocaine- and amphetamine-regulated transcript, agouti-related peptide, and neuropeptide Y. Beyond the brain, Kp is expressed in peripheral tissues involved in metabolic functions. In this review, we will mainly focus on the local action of this peptide in peripheral organs such as the pancreas, liver, and the adipose tissue. We will concentrate on dysregulation of the Kp system in cases of metabolic imbalance, e.g., obesity and diabetes. Importantly, these patients besides metabolic health problems often suffer from disruptions of the reproductive system, manifested by abnormalities in menstrual cycles, premature child birth, miscarriages in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, and infertility. We will review the evidence from animal models and clinical data indicating that Kp could serve as a promising agent with clinical applications in regulation of reproductive problems in individuals with obesity and diabetes. Finally, emerging data indicate a role of Kp in regulation of insulin secretion, potentially leading to development of further therapeutic uses of this peptide to treat metabolic problems in patients with these lifestyle diseases.

Klinefelter syndrome and fertility-Impact of X-chromosomal inheritance on spermatogenesis.

With the use of testicular sperm extraction (TESE), spermatozoa can be retrieved in about 30%-50% of men with Klinefelter syndrome (KS). The reason for the absence or presence of spermatozoa in half of the men with KS remains unknown. Therefore, the search for an objective marker for a positive prediction in finding spermatozoa is of significant clinical value to avoid unnecessary testicular biopsies in males with (mostly) low testicular volume and impaired testosterone. The objective of this study was to determine whether paternal or maternal inheritance of the additional X-chromosome can predict the absence or presence of spermatogenesis in men with KS. Men with KS who have had a testicular biopsy for diagnostic fertility workup TESE were eligible for inclusion. Buccal swabs from nine KS patients and parents (trios) were taken to compare X-chromosomal inheritance to determine the parental origin of both X-chromosomes in the males with KS. Spermatozoa were found in TESE biopsies 8 of 35 (23%) patients after performing a unilateral or bilateral TESE. Different levels of spermatogenesis (from the only presence of spermatogonia, up to maturation arrest or hypospermatogenesis) appeared to be present in 19 of 35 (54%) men, meaning that the presence of spermatogenesis not always yields mature spermatozoa. From the nine KS-trios that were genetically analysed for X-chromosomal inheritance origin, no evidence of a correlation between the maternal or paternal origin of the additional X-chromosome and the presence of spermatogenesis was found. In conclusion, the maternal or paternal origin of the additional X-chromosome in men with KS does not predict the presence or absence of spermatogenesis.

ВПЛИВ СТРУМЕКТОМІЇ НА СТАН ГЕМОМІКРОЦИРКУЛЯТОРНОГО РУСЛА ЯЄЧОК ЩУРІВ ЗА ДАНИМИ ЕЛЕКТРОННОЇ МІКРОСКОПІЇ

Резюме. За останні роки відмічається досить стійка тенденція до зниження народжуваності в ряді європейських країн, включаючи Україну. Одним з факторів зниження цього показника вважається ослаблення активності сперматогенезу. До причин порушення сперматогенезу у чоловіків відносять ендокринні розлади. Зокрема, за результатами ряду досліджень висловлюється думка, що до порушення сперматогенної та інкреторної функції сім’яників у дорослих чоловіків може приводити нестачі тиреоїдних гормонів.Мета дослідження: встановити ультраструктурні особливості перебудови гемомікроциркуляторного русла яєчок щурів після струмектомії.Матеріал і методи. Експерименти проведено на 18 статевозрілих білих лабораторних щурах-самцях з масою тіла 160-180 г. З них 3 тварини склали контрольну групу Іншим 15 щурам під кетаміновим знечуленням проводили струмектомію. Матеріал для електронномікроскопічних досліджень забирали через 1, 3, 7, 14 і 28 діб після операції згідно загальноприйнятої методики. Ультратонкі зрізи, виготовлені на ультрамікротомі LKB–3 (Швеція), контрастували 1 % водним розчином уранілацетату та цитратом свинцю згідно метода Рейнольдса і вивчали в електронному мікроскопі ПЕМ–125К.Результати досліджень та їх обговорення. Через 1 добу після струмектомії спостерігалося зниження пропускної здатності гемокапілярів за рахунок помітного звуження їх просвіту. Це відбувалося внаслідок набухання ендотеліоцитів і особливо їх ядер, які разом із тонким прошарком цитоплазми і цитолемою випиналися у просвіт мікросудин. У результаті цього у просвіті гемокапілярів виявлялися скупчення овально деформованих еритроцитів.Через 3 доби після струмектомії діаметр гемокапілярів ставав, навпаки, дещо розширеним. У їх просвіті також були присутні формені елементи крові, переважно еритроцити, форма яких ще продовжувала залишатися овально витягнутою. Ендотеліоцити у складі стінок мікросудин мали потовщену вогнищево набряклу цитоплазму. Цитолема за рахунок нерівності контурів формувала випинання та мікроворсинки у просвіт капілярів, а також заглиблення у цитоплазму. У периферійних ділянках цитоплазми виявлялися різні за розмірами вакуолі та піноцитозні міхурці. На цьому тлі відмічалися локальні потовщення базальної мембрани та периваскулярний набряк.З 7 по14 добу експериментального спостереження виявлені попередньо електронномікроскопічні зміни структур гемомікроциркуляторного русла продовжували наростати. Це підтверджувалося подальшим розширенням просвітів та помітним кровонаповненям мікросудин. Зберігалися випинання і інвагінації цитоплазми ендотеліоцитів. Однак товщина їх цитоплазми, особливо у периферійних відділах, дещо зменшувалася.Починаючи з 21 і особливо на 28 добу експерименту виявлені у попередній термін спостереження ознаки розладів гемомікроциркукляції продовжували наростати. Просвіт гемокапілярів ставав помітно розширеним і нерідко у рази переважав над діаметром еритроцитів, які у результаті цього набували чіткої округлої форми. У складі стінок мікросудин одночасно виявлялися ендотеліоцити з набряком цитоплазми, а також клітини, що мали електроннощільну цитоплазму та пікнотичні осміофільні ядра. У розширених периваскулярних просторах виявлялися ознаки склеротичних змін, що підтверджувалося наявністю як окремих колагенових фібрил, так і цілих їх пучків.Висновки. У ранні терміни після струмектомії знижується пропускна здатність гемокапілярів яєчок як реакція на операційну травму. У віддалені терміни у гемомікроциркуляторному руслі яєчок переважають явища застійного характеру з одночасним розвитком дистрофічних змін у ендотеліоцитах та проліферацією колагенових структур у периваскулярних просторах, що може бути причиною ішемії органа з розвитком його функціональної недостатності.

Sodium-dependent organic anion transporter (Slc10a6−/−) knockout mice show normal spermatogenesis and reproduction, but elevated serum levels for cholesterol sulfate

The sodium-dependent organic anion transporter SOAT (gene name SLC10A6 in man and Slc10a6 in mice) is a plasma membrane transporter for sulfated steroids, which is highly expressed in germ cells of the testis. SOAT can transport biologically inactive sulfated steroids into specific target cells, where they can be reactivated by the steroid sulfatase (STS) to biologically active, unconjugated steroids known to regulate spermatogenesis. Significantly reduced SOAT mRNA expression was previously found in different forms of impaired spermatogenesis in man. It was supposed that SOAT plays a role for the local supply of steroids in the testis and consequently for spermatogenesis and fertility. Thus, an Slc10a6−/− Soat knockout mouse model was established by recombination-based target deletion of the Slc10a6 gene to elucidate the role of Soat in reproduction. However, the Slc10a6−/− knockout mice were fertile, produced normal litter sizes, and had normal spermatogenesis and sperm vitality. This phenotype suggests that the loss of Soat can be compensated in the knockout mice or that Soat function is not essential for reproduction. In addition to reproductive phenotyping, a comprehensive targeted steroid analysis including a set of 9 un-conjugated and 12 sulfo-conjugated steroids was performed in serum of Slc10a6−/− knockout and Slc10a6+/+ wildtype mice. Only cholesterol sulfate, corticosterone, and testosterone (only in the males) could be detected in considerable amounts. Interestingly, male Slc10a6−/− knockout mice showed significantly higher serum levels for cholesterol sulfate compared to their wildtype controls. As cholesterol sulfate has a broader impact apart from the testis, further analysis of this phenotype will include other organs such as skin and lung, which also show high Soat expression in the mouse.

Clomiphene citrate rescue of spermatogenesis in men with infertility while remaining on finasteride: A case report.

Finasteride is a selective inhibitor of type-2 5-alpha reductase enzyme, preventing the conversion of testosterone to dihydrotestosterone (DHT). Finasteride is used as an oral drug for the treatment of benign prostatic hyperplasia at the 5 mg/day dose and is also used for the treatment of androgenic alopecia, or male pattern hair loss, at a dosage of 1 mg orally. There are now a number of studies documenting that finasteride, even at the low dose of 1 mg, may have an adverse effect on fertility for some men.In the largest study, Samplaski et al reported that sperm counts improved over 11-fold once the men had stopped the finasteride, but most of the men did not recover to normal sperm parameters. Presently, if men using finasteride are subfertile, the recommendation is to stop the finasteride and wait for a recovery of spermatogenesis. There has been no report of the use of any hormone therapy, such as clomiphene citrate, gonadotropin, or aromatase inhibitors, to treat subfertile men on finasteride. This is the first case report of the use of clomiphene citrate to improve fertilty for a man on finasteride.

An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism

BackgroundHypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH.MethodsThis was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 106/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs).ResultsMean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 106/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated.ConclusionsCorifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone.Trial registrationClinicalTrials.gov: NCT01709331.

Peculiarities in Disturbance of Spermatogenesis in Men with Infertility in Dependence on the Used Assisted Reproductive Technologies

The work represents the results of analysis of spermograms in men with infertility of 420 married couples who referred during 2013–2015 to the Institute of Reproductive Medicine (Kyiv) for fertilization with the aim to restore fertility. There were revealed the parameters of dependence of the used programs of the assisted reproductive technologies. Based on the quantitative assessment in scores, the most informative significant spermograms, determining the choice of technology, were selected.

Gonadotropin Induction of Spermatogenesis in Men with Hypogonadotrophic Hypogonadism: an audit

Gonadotropin Induction of Spermatogenesis in Men with Hypogonadotrophic Hypogonadism: an audit

Identifying differential mRNA & miRNA expression patterns in microsurgically isolated individual seminiferous tubules reveals unique “niche” for spermatogenesis in men with severe forms of infertility

Non-obstructive azoospermia (NOA) is a cause of male infertility secondary to genetically driven defects in spermatogenesis. Testicular sperm extraction (TESE) is successful in identifying small number of sperm in 50% of men with NOA. During TESE, predominantly collapsed seminiferous tubules (ST) are identified with rare areas of dilated STs that are more likely to harbor viable sperm. Hence we hypothesize that miRNA regulated control of mRNA expression along STs leads to optimal environments for spermatogenesis within the human testis.