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Asian Journal of Andrology logoLink to Asian Journal of Andrology
. 2024 Oct 18;27(2):231–238. doi: 10.4103/aja202478

Study on the influence of the sY1192 gene locus in the AZFb/c region on sperm quality and pregnancy outcome

Gang-Xin Chen 1,✉, Yan Sun 1,2,✉, Rui Yang 1, Zhi-Qing Huang 1, Hai-Yan Li 1, Bei-Hong Zheng 1,3
PMCID: PMC11949456  PMID: 39420567

Abstract

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.

Keywords: assisted reproductive technology, AZFb/c, pregnancy outcome, sY1192, Y chromosome microdeletion

INTRODUCTION

The microdeletion of the Y chromosome is an important cause of spermatogenic dysfunction in men. The causes of the loss of small fragments of the Y chromosome include genetic and external factors, such as drugs and radiation, among which the most important reason is genetic factors.1,2 Related studies have shown that the incidence of Y chromosome microdeletions in the infertile male population is about 1 in 4000, only second to Klinefelter syndrome in genetic causes of male infertility.3 The Y chromosome is a unique male sex chromatid that consists of a long arm (Yq) and a short arm (Yp), with 5% pseudoautosomal (PAR). The segments between the PAR regions are called the male-specific region (MSY), which consists of the X transposition sequence (XTR), a degenerate X sequence (XDG), and amplified sequence.4 There is a gene controlling sperm generation in the Y chromosome called the azoospermia factor (AZF). Its gene is located in the long arm of the Y chromosome 6, called Yq 11, which controls the occurrence of spermatocytes, male germ cell meiosis, and sperm maturation.5

The AZF region is rich in highly similar palindromic structures (P1–P8).4 As these gene sequences are repetitive structures, this region is prone to insertion, deletion, inversion, duplication, and other gene mutations, making the Y chromosome more prone to microdeletions in the AZF region than other chromosomes.6 We divided the Yq11 region, which dominates spermatogenesis, into AZFa/b/c regions. The AZFa region is located at the proximal end of the Y chromosome, and its deletion causes Sertoli cell-only syndrome (SCOS); most patients are clinically azoospermic. The AZFb region is located in the middle segment, and its deletion causes spermatocyte arrest; patients are also clinically azoospermic. The AZFc region is located distally (the AZFb and AZFc regions overlap), and patients may present with normozoospermia, oligozoospermia, asthenozoospermia, or azoospermia.7,8 The most common type of deletion in clinic is AZFc deletion, which has six different amplicon family sequences on AZFb and AZFc, named after fluorescent probes of different colors.8 These amplicons are all multicopy sequences, with a base similarity of over 99.9%.9

Many methods can be used to detect AZF microdeletions, and the European Association of Urology and the European Molecular Genetics Quality Network (EAA/EMQN) recommend a sequence tag site (STS) marker multiplex polymerase chain reaction (PCR) to detect the microdeletions of AZF. EAA/EMQN suggests the detection of the Y chromosome microdeletions using six STS marker loci, including sY84 and sY86 for AZFa, sY127 and sY134 for AZFb, and sY254 and sY255 for AZFc, with 95% of the AZF microdeletion types detected.3,10 We used six sites recommended by the EAA and added eight expanded sites and heterosomal tags (sY160) to improve the detection rate of the deletions in the AZF region. This study focused on a model in which sY1192 deletion occurs in AZF microdeletions and how it differs from the traditional mirror structure. SY1192 is located in the overlapping region between AZFb and AZFc. The specific location is in the distal part of AZFb, which is the u3 region between b2 and g1 of the AZFc band.10,11,12 The u3 region belongs to a nonpalindromic sequence in AZFb/c and is less prone to repair after deletion occurs than in the mirror structure.9

The AZF microdeletion changes the environment of developing spermatozoa. This is mainly manifested as the loss of different genetic loci causing changes in the sex hormone levels, which cause decreased sperm number and function and even azoospermia.13 Although men with oligozoospermia, asthenozoospermia, or azoospermia have a low chance of conception naturally, intracytoplasmic sperm injection (ICSI) allows these men to have children.14 Although such patients have lower fertilization and cleavage rates with this technique than those with normal chromosomes, it does not affect the pregnancy rate.14 Related studies have shown no difference in pregnancy rates among different types of microdeletion patients using the ICSI technique.14,15,16,17 There are a few literature on pregnancy outcomes with sY1192 single-locus deletions. We analyzed pregnancy outcomes after assisted reproduction in such patients.

PATIENTS AND METHODS

Patients and experimental design

A total of 2000 patients underwent assisted reproductive therapy at Fujian Maternity and Child Health Hospital (Fuzhou, China) between January 2018 and December 2022. Multiplex PCR was used to screen 116 patients with AZF microdeletion on the Y chromosome. Loss of the Y chromosome sY1192 locus and other types of microdeletions were analyzed. The patients’ semen quality (ejaculated spermatozoa and testicular biopsy spermatozoa were used) and peripheral blood sex hormone levels were examined. Appropriate assisted reproductive technology was selected according to the condition of the husband and wife, and the embryo quality and pregnancy outcomes were analyzed.

Informed consent was obtained from the patients for the study, and the study was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital (Approval No. 2023KY093). The study obtained permission to publicly publish the data. All methods were carried out in accordance with the relevant guidelines and national regulations.

Molecular detection of the Y chromosome

The peripheral blood of the patients was collected, and DNA extraction, PCR amplification, gel electrophoresis, and result interpretation were performed according to the standard experimental operation procedures of the relevant DNA extraction kit (Shenzhen Yaneng Biotechnology Co., Ltd., Shenzhen, China). The PCR amplification reaction included the following: a total reaction system of 22 μl, comprising 8.0 μl ddH2O, 13.5 μl reaction liquid I (primer, UNG enzyme, dNTP, dUTP, Mg2+, and buffer system), and 0.5 μl DNA polymerase. The PCR reaction conditions were as follows: UNG enzyme reaction at 50°C for 10 min; predenaturation at 95°C for 15 min; denaturation at 94°C for 30 s, 58°C for 60 s, and 72°C for 60 s for 35 cycles; and extension at 72°C for 10 min. Gel electrophoresis proceeded as follows: after PCR amplification, 1–2 μl 6× loading buffer was added to the PCR tube, and 5 μl sample was mixed with 2% (w/v) agarose gel at an electrophoresis voltage of 120 V and electrophoresis time of 25 min. The ultraviolet detector results were observed, and the electrophoresis results were recorded.

According to the EAA/EMQN guidelines,3 a multiple PCR technique was used to detect sY84, sY86, sY127, sY134, sY254, sY255, sY82, sY88, sY1064, sY106.5, sY105, sY121, sY153, sY1192, sY160, zinc finger X/Y gene (ZFX/Y), and sex-determining region of Y chromosome gene (SRY). ZFX/Y and SRY were used for quality control. The results were analyzed using agarose gel electrophoresis. After electrophoresis, amplification bands appeared on the length of the target gene fragment in the test sample and normal control sample, while no amplification bands were observed in the negative and blank control samples, indicating the existence of the gene locus. The electrophoresis results of the test sample did not show any amplification bands, while the gene of the positive control sample showed normal bands, indicating that the gene locus is missing.

Sperm detection

The concentration and motility of spermatozoa were determined through manual counting, as recommended by the World Health Organization.18 The patients abstained for 2–7 days, and semen was obtained and kept in a 37°C warm chamber for 30–60 min. About 10 μl of the liquefied semen was added to the Makler plate (American Natural Genetics Co., Ltd., Haifa, Israel) to assess the sperm concentration. If no spermatozoa were found, the liquefied semen were sampled twice more. If spermatozoa were still not detected after high-speed centrifugation, azoospermia was diagnosed.

Hormone detection

Fasting venous blood was collected, and the follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2), and testosterone (T) levels were measured by electrochemiluminescence (American Standard Biotechnology Co., Ltd., Nanjing, China). None of the patients took hormonal drugs.

Assisted reproductive technology to assist pregnancy

Different pregnancy aid methods were selected according to age, body mass index, anti-Müllerian hormone level, basal follicle number, basal hormone level, endometrial thickness, and ovarian reserve function of both men and women. Women received an appropriate in vitro fertilization (IVF) regimen to induce ovulation through the injection of different doses of agonist or antagonist. Oocytes were recorded under the guidance of vaginal ultrasound, and different schemes were selected for assisted reproduction according to sperm quality (IVF, ICSI, artificial intrauterine insemination [AIH], artificial insemination with donor [AID], or sperm donor IVF). Embryonic quality was assessed, and pregnancy outcomes were observed.19,20,21

Statistical analyses

Data analysis was performed using SPSS 26.0 statistical software (IBM, Armonk, NY, USA). The measurement data were expressed as mean±standard deviation (s.d.). An independent sample’s t-test was conducted if the data were normally distributed. A continuous corrected Chi-squared test was performed. P < 0.05 was considered statistically significant.

RESULTS

Type and proportion of missing AZF

Among the 116 cases of AZF microdeletions, the sY1192 unit point deletion accounted for 41.4% (48/116), AZFc deletion accounted for 40.5% (47/116), AZFb deletion accounted for 2.6% (3/116), AZFa deletion accounted for 3.4% (4/116), AZFb/c common deletion accounted for 7.8% (9/116), AZFa/b/c common deletion accounted for 3.4% (4/116), and sY1153-independent deletion occurred in one case. SY1192 can be accompanied by common deletions at other loci. This manifested as sY1192 with AZFc deletions, accounting for 18.1% (21/116) of the total cases and 44.7% (21/47) of the AZFc deletions. Among the AZFb deletion samples, there was one case of sY1192 deletion, accounting for 33.3% (1/3). In four cases of AZFa deficiency, there was no sY1192 deficiency; and 55.6% (5/9) of AZFb/c codeletions were associated with sY1192 deletion. Among the four AZFa/b/c codeletion samples, 50.0% (2/4) were accompanied by an sY1192 deletion. In the analysis results, one case of sY1192, accompanied by a common deletion of sY153, was found (Figure 1).

Figure 1.

Figure 1

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Structure and missing segments of the AZF region of the Y chromosome. (a) The Y chromosome consists of a long arm, a short arm, and a functional area. (b) The AZF regions have a palindrome structure. These regions contain a series of highly similar positive and negative repetitive sequences that encode the sex-determining region of Y chromosome gene (SRY) responsible for male gender. The amplicon of these regions includes eight classic palindrome structures (P1–P8).4 (c) The AZF region also contains multiple copy family sequences of different amplicons, which are named after fluorescent probes of different colors: blue (b), turquoise (t), green (g), red (r), yellow (y), and gray (gr).8 u represents nonsingle copy sequences. (d) The sequence tag site (STS) labeled with multiple PCR markers corresponds to the sequence position of the AZF region. (e) In 116 cases, the missing AZF region was observed, and its location and proportion are shown. PCR: polymerase chain reaction; PR: pseudo autosomal region; AZF: azoospermia factor; Yp: short Y arm; Yq: long Y arm.

Detection rate of the sY1192 unit point deletion and other site deletion types

According to the statistics of the traditional AZF partition, the azoospermia rate caused by an independent absence of AZFc was 44.7% (21/47), and the severe oligozoospermia rate was 55.3% (26/47), with no normozoospermia detected. The azoospermia rate was 100.0% in patients with AZFa, AZFb, AZFb/c, and AZFa/b/c deletions. According to the statistics of sequence tagged sites (STS) loss sites, among patients with the sY1192 unit point deletion, the azoospermia rate was 47.9% (23/48), the severe oligozoospermia rate was 50.0% (24/48), and the probability of normozoospermia was 2.1% (1/48). An azoospermia rate of 50.0% (15/30) was found in the codeletion type of the sY1192 locus with other loci. An azoospermia rate of 68.4% (26/38) was found in patients with the presence of the sY1192 locus but the absence of other loci. A special patient with sY1192 and a single deletion of the sY153 locus presented with oligozoospermia (Figure 2 and 3).

Figure 2.

Figure 2

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The 8 microdeletion models related to sY1192 deletion. The AZF regions correspond to eight types of sY1192 missing models, which are named after fluorescent probes of different colors: blue (b), turquoise (t), green (g), red (r), yellow (y), and gray (gr).8 u represents nonsingle copy sequences. The newly discovered missing type is indicated by green, while the type with the highest incidence is indicated by red. AZF: azoospermia factor.

Figure 3.

Figure 3

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The sperm detection rates of different types of microdeletions related to sY1192. The detection rate of spermatozoa with sY1192 single deletion and sY1192 combined with other site deletions was not significantly different (52.1% vs 50.0%). However, there was a noticeable statistical difference in the detection rate of spermatozoa with other types of deletions present in sY1192 (52.1% vs 31.6%). sY1192-: sY1192 locus lost; sY1192+ other-: sY1192 and other loci are lost; other-: sY1192 locus exists, while other loci missed; +: detected sperm; −: undetected sperm.

Effect of sY1192 deficiency and other types of microdeletions on male hormone levels

The serum FSH and LH levels in patients with the three types of microdeletions were higher than those in the normal control group, and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the PRL levels between the three groups of AZF microdeletion patients and the normal control group (all P > 0.05). No statistically significant difference was found in the FSH, LH, and E2 levels among the three groups of microdeletions (all P > 0.05). The T levels of the sY1192 unit point defect group and the accompanying defect group were similar to those of the normal group (P > 0.05). The T levels of the other site loss groups were lower than those of the above three groups, and the differences were statistically significant (P < 0.05), as shown in Figure 4.

Figure 4.

Figure 4

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The hormone levels in patients with different types of microdeletions. The (a) LH, (b) PRL, (c) T, (d) E2, and (e) FSH levels among different types of deletions. *P<0.05, statistically significant difference between the two groups. sY1192-: sY1192 locus lost; sY1192+ other-: sY1192 and other loci are lost; other-: sY1192 locus exists, while other loci missed; LH: luteinizing hormone; FSH: follicle-stimulating hormone; PRL: prolactin; T: testosterone; E2: estradiol.

Pregnancy outcomes after assisted reproductive technology for sY1192 and other types of microdeletions

According to the flowchart, 116 patients underwent the corresponding assisted reproductive technology for pregnancy. The pregnancy outcomes of 48 patients with sY1192 deletion were as follows: 1 patient underwent IVF but his wife did not conceive; 2 patients with normal spermatozoa underwent AIH, resulting in two pregnancies; 2 patients underwent donor IVF, resulting in one pregnancy; 20 patients with azoospermia or minimal spermatozoa chose AID, resulting in 11 pregnancies; and 23 oligozoospermic patients chose ICSI, resulting in 17 pregnancies. The pregnancy outcomes of 68 patients with other types of microdeletions were as follows: 28 cases selected donor IVF, resulting in 11 pregnancies; 26 cases chose AID, resulting in 20 pregnancies; 12 oligozoospermic patients chose ICSI, resulting in 9 pregnancies; and two patients abandoned assisted reproductive technology treatment. Thirty-five patients underwent ICSI-assisted pregnancy, including 23 cases with sY1192 deletion and 12 cases with sY1192 presence. There was no difference in their pregnancy rates (P > 0.05), but the fertilization rate and cleavage rate of the sY1192 unit point deletion group were higher than those of the other deletion groups (both P < 0.05; Figure 5 and Table 1).

Figure 5.

Figure 5

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Impact of microdeletion on pregnancy outcomes. (a) Pregnancy outcomes in patients with various microdeletions following assisted reproduction. (b) Pregnancy rate after ICSI in patients with different types of deletions (sY1192 vs other: 56.5% vs 58.3%). The pregnancy rate represents the utilization of all embryos. (c) Blastocyst formation rate after ICSI in patients with different types of deletions (sY1192 vs other: 57.7% vs 59.2%). (d) Variation in fertilization rates among patients with different types of deletions after ICSI. (e) Differences in cleavage rate after ICSI among patients with different types of deletions. (f) No significant difference in the rate of excellent embryos after ICSI among patients with different types of deletions. *P<0.05, statistically significant difference between the two groups. sY1192-: sY1192 locus lost; +: positive; −: negative; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; AIH: artificial intrauterine insemination; AID: artificial insemination with donor; G-IVF: using sperm provided by others for in vitro fertilization.

Table 1.

Patient status and pregnancy outcomes for two different microdeletion types

Parameter (female) sY1192− (n=23) sY1192+ (n=12) t/χ2 P
Age (year), mean±s.d. 30.7±3.4 28.8±3.4 1.571 0.775
BMI (kg m−2), mean±s.d. 21.05±2.69 21.25±2.18 −0.218 0.724
Duration of infertility (year), mean±s.d. 3.5±2.8 3.8±3.3 −0.215 0.380
Endometria (mm), mean±s.d. 11.26±1.90 11.59±1.92 −0.486 0.962
Egg (n), mean±s.d. 14.4±7.2 13.3±6.6 0.441 0.831
AMH (ng ml−1), mean±s.d. 4.42±2.48 5.44±4.90 3.259 0.418
Basal follicle (n), mean±s.d. 16.09±5.17 17.50±8.92 2.295 0.555
FSH (mIU ml−1), mean±s.d. 5.86±1.74 6.36±1.77 0.039 0.432
LH (mIU ml−1), mean±s.d. 3.62±1.93 4.88±2.78 0.800 0.124
PRL (ng ml−1), mean±s.d. 18.33±5.57 16.23±8.48 1.055 0.384
E2 (pg ml−1), mean±s.d. 40.17±28.59 38.23±19.43 0.280 0.834
Testosterone (ng ml-1), mean±s.d. 0.29±0.09 0.31±0.12 0.491 0.563
Fertility rate (%), mean±s.d 85.33±13.52 78.56±19.70 1.200 0.006*
Cleavage rate (%), mean±s.d 95.93±7.03 90.95±16.05 1.283 0.010*
Excellent embryo rate (D3, %), mean±s.d 59.22±21.24 63.12±17.30 −0.548 0.670
Blastocyst rate (D5 and D6), % (n/total) 57.7 (56/97) 59.2 (29/49) 0.028 0.867a
Pregnancy rate (D3, D5 and D6), % (n/total) 56.5 (13/23) 58.3 (7/12) 0.011 0.918a
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*P<0.05, statistically significant difference; aChi-square test. +: positive; –: negative; BMI: body mass index; AMH: anti-Müllerian hormone; FSH: follicle-stimulating hormone; LH: luteinizing hormone; PRL: prolactin; E2: estradiol; D3/5/6: embryo growth time (3/5/6 days); s.d.: standard deviation

DISCUSSION

Microdeletions in the AZF region of the Y chromosome are an important cause of azoospermia and oligoasthenozoospermia, and its incidence in the infertile male population is 5.7%–21.0%.22 There are significant racial and regional differences in the probability and type of AZF microdeletions, with an incidence rate of 8%–18% in Europe and 6.7%–13.0% in Asia.23,24 AZFc deletion is the main type of Y chromosome deletion in all regions, and the AZFc microdeletion rate in some regions exceeds 80%.3,22 The nonallelic homologous recombination mediated by the amplicon of the MSY sequence is the direct cause of AZF microdeletion, but external environmental factors can also indirectly cause microdeletion.1,2 Examining microdeletion fragments and types of AZF can help in the diagnosis and treatment of male infertility.

After PCR amplification with STS, electrophoresis can mark the corresponding gene sites of the Y chromosome, and genes at different sites encode different functional regions.3,10 We used “u” to represent nonsingle copy sequences in this region, where u1, u2, and u3 appear only once. The homology between u3 and Yp was 99.7%, and the sY1192 site represents the presence of u3.12 The sY1192 site is located in the overlapping area of AZFb and AZFc, specifically at the distal end of the AZFb and u3 area10,11,12 between b2 and g1 of the AZFc band. The deletion of sY1192 or sY1191 represents a b2/b3-type deletion in the AZFc region.12,25 Owing to the high specificity of sY1192 as a single copy site between g1 and b2, its deletion is more specific than the other mirror structure sites in the AZF region.

In this study, 41.4% of the 116 patients with AZF microdeletions had sY1192-independent deletions, indicating that sY1192-independent deletions are a common phenomenon in AZF microdeletions. SY1192 can also exist in the form of codeletion with other loci. There are eight modes of such deletion. These deletion sites were divided into five types according to the AZF partition: sY1192 single-locus deletion, AZFc, AZFb, AZFb/c, and AZFa/b/c. A case of the deletion type of sY1192 with sY153 was also found. Our study showed that the rate of sperm detection in men with an independent deletion of sY1192 was higher than that of the other types of microdeletions. The probability of azoospermia in patients with AZFa, AZFb, AZFb/c, and AZFa/b/c deletions was 100.0%. A patient with sY1192 and a single deletion of the sY153 locus presented with oligozoospermia. The above results show that the negative effect of the sY1192 unit point deletion on spermatogenesis is less than that of other mixed-type microdeletions of the Y chromosome, and that the size of the gene locus loss segment is positively correlated with the integrity of cell function. The absence of a single gene locus in the AZF region represents only a mutation or absence at that locus, while the loss of multiple loci represents the loss of the entire gene fragment. This loss of large fragments is more difficult to repair and has a greater effect on sperm function.9,26

Hormone levels are important factors in maintaining the environment for spermatogenesis. Microdeletion of the Y chromosome causes changes in the male hormone level, which is related to the type of deletion.27,28 The levels of sex hormones, such as FSH, play an important role in maintaining male reproductive ability, and their secretion is regulated by the hypothalamic–pituitary–testicular axis. Our study showed that the FSH, LH, and T levels in the sY1192 deletion group were higher than those in normal individuals, with T levels higher than the other types of microdeletions. This result is similar to the effect of other types of AZF microdeletions on hormone levels.29 The change in male hormone levels may be indicative of the occurrence of AZF microdeletions and the deterioration of sperm quality, but is not predictive of the quality of pregnancy outcomes.30 The mechanism may be that the proteins encoded by Y chromosome-related genes affect the seminiferous tubules, which support cells and gonadal organs, ultimately leading to corresponding changes in hormones.

The homologous recombination of AZF region amplifiers during meiosis is an important mechanism of Y chromosome microdeletion.31 There are three ways to form and transmit microdeletions: de novo deletions,7,32,33 vertical inheritance,34 and the formation of missing chimeras.35 With the advent of ICSI, the spouses of patients with azoospermia or severe oligoasthenozoospermia caused by the microdeletion of the Y chromosome can successfully conceive. However, this technology can lead to the introduction of spermatozoa with microdeletions of the above three forms of gene fragments into the oocyte cytoplasm, thereby passing on microdeletions to the offspring. Some studies have found that the probability of Y chromosome microdeletions in the offspring of ICSI-assisted pregnancies is 3.2% or 9.4%, which is similar to the probability of Y chromosome microdeletions in infertile male patients.36,37 At present, few studies have been conducted on the effect of the single-site deletion of AZF on pregnancy outcomes, and there are no relevant reports on the effect of single-site deletion of sY1192 on pregnancy outcomes. The results of this study are similar to that examining the effect of a single-site deletion in sY152 on pregnancy outcomes, with both showing differences in fertilization rate and cleavage rate after ICSI compared with the other types of microdeletions but showing no difference in pregnancy outcomes among the different types of microdeletions.38 The study found that the single-site deletion of sY1192 resulted in higher fertilization and cleavage rates than ICSI used with other mixed-type deletions. This result indirectly indicates that the quality of spermatozoa with the sY1192 unit point deletion is higher than that of the other types of microdeletions, which is consistent with the higher detection rate of spermatozoa with the sY1192 unit point deletion in the study and with the findings of Stouffs et al.39 that the sY1192 site could be used as a testicular biopsy marker. The discovery of this phenomenon provides a basis for the diagnosis and treatment of Y chromosome microdeletion.

CONCLUSION

The unit point deletion of sY1192 is a common phenomenon in AZF microdeletions. Five types of AZF regions were found to be associated with the loss of the sY1192 locus, which could be manifested in eight forms. The independent absence of sY1192 had less effect on sperm quality than the other types of microdeletions, and the changes in male hormone levels were similar to the other types of microdeletions. The fertilization rate and cleavage rate of oocytes injected with spermatozoa bearing a single-point deletion in sY1192 were higher than those with other types of microdeletions, but their pregnancy outcomes were similar.

AUTHOR CONTRIBUTIONS

GXC conceived and designed the research plan, analyzed the data, and wrote the manuscript. YS, ZQH, RY, HYL, and BHZ participated in the data collection and analysis. YS participated in drafting the manuscript. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.

ACKNOWLEDGMENTS

We would like to thank the technicians of the Male Health Laboratory in the reproductive center of Fujian Maternity and Child Health Hospital for the sample reception and processing. This work was supported by the funding from the Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant No. 2023Y9385), and Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province, China (Grant No. 2022ZQNZD010).

REFERENCES

  • 1.O’Flynn O’, Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility:a review. Fertil Steril. 2010;93:1–12. doi: 10.1016/j.fertnstert.2009.10.045. [DOI] [PubMed] [Google Scholar]
  • 2.Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol. 2018;15:369–84. doi: 10.1038/s41585-018-0003-3. [DOI] [PubMed] [Google Scholar]
  • 3.Simoni M, Bakker E, Krausz C. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions. State of the art 2004. Int J Androl. 2004;27:240–9. doi: 10.1111/j.1365-2605.2004.00495.x. [DOI] [PubMed] [Google Scholar]
  • 4.Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003;423:825–37. doi: 10.1038/nature01722. [DOI] [PubMed] [Google Scholar]
  • 5.Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet. 1976;34:119–24. doi: 10.1007/BF00278879. [DOI] [PubMed] [Google Scholar]
  • 6.Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS, et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature. 2003;423:873–6. doi: 10.1038/nature01723. [DOI] [PubMed] [Google Scholar]
  • 7.Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996;5:933–43. doi: 10.1093/hmg/5.7.933. [DOI] [PubMed] [Google Scholar]
  • 8.Vogt PH. AZF deletions and Y chromosomal haplogroups:history and update based on sequence. Hum Reprod Update. 2005;11:319–36. doi: 10.1093/humupd/dmi017. [DOI] [PubMed] [Google Scholar]
  • 9.Fernandes S, Paracchin S, Meyer LH, Floridia G, Tyler-Smith C, et al. A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup N. Am J Hum Genet. 2003;74:180–7. doi: 10.1086/381132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Krausz C, Hoefsloot L, Simoni M, Tüttelmann F. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions:state-of-the-art 2013. Andrology. 2014;2:5–19. doi: 10.1111/j.2047-2927.2013.00173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Vogt PH, Bender U, Deibel B, Kiesewetter F, Zimmer J, et al. Human AZFb deletions cause distinct testicular pathologies depending on their extensions in Yq11 and the Y haplogroup:new cases and review of literature. Cell Biosci. 2021;11:60. doi: 10.1186/s13578-021-00551-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Kuroda-Kawaguchi T, Skaletsky H, Brown LG, Minx PJ, Cordum HS. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet. 2001;29:279–86. doi: 10.1038/ng757. [DOI] [PubMed] [Google Scholar]
  • 13.Oates RD, Silber S, Brown LG, Page DC. Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod. 2002;17:2813–24. doi: 10.1093/humrep/17.11.2813. [DOI] [PubMed] [Google Scholar]
  • 14.Zhu YC, Wu TH, Li GG, Yin B, Liu HJ. Decrease in fertilization and cleavage rates, but not in clinical outcomes for infertile men with AZF microdeletion of the Y chromosome. Zygote. 2014;23:771–7. doi: 10.1017/S096719941400046X. [DOI] [PubMed] [Google Scholar]
  • 15.Liu XH, Qiao J, Li R, Yan LY, Chen LX, et al. Y chromosome AZFc microdeletion may not affect the outcomes of ICSI for infertile males with fresh ejaculated sperm. J Assist Reprod Genet. 2013;30:813–9. doi: 10.1007/s10815-013-0009-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Abur U, Gunes S, Ascı R, Altundag E, Akar OS, et al. Chromosomal and Y-chromosome microdeletion analysis in 1,300 infertile males and the fertility outcome of patients with AZFc microdeletions. Andrologia. 2019;51:e13402. doi: 10.1111/and.13402. [DOI] [PubMed] [Google Scholar]
  • 17.Liu XY, Wang RX, Fu Y, Luo LL, Guo W, et al. Outcomes of intracytoplasmic sperm injection in oligozoospermic men with Y chromosome AZFb or AZFc microdeletions. Andrologia. 2016;49:e12602. doi: 10.1111/and.12602. [DOI] [PubMed] [Google Scholar]
  • 18.World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. Geneva: World Health Organization; 2010. pp. 45–100. [Google Scholar]
  • 19.Xu H, Feng G, Wang H, Han Y, Yang R, et al. A novel mathematical model of true ovarian reserve assessment based on predicted probability of poor ovarian response:a retrospective cohort study. J Assist Reprod Genet. 2020;37:963–72. doi: 10.1007/s10815-020-01700-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Kromp F, Balaban B, Cottin V, Saiz I, Fancsovits P, et al. O-285 artificial intelligence algorithms reach expert-level accuracy in automated grading of blastocyst morphology assessment based on static embryo images and Gardner criteria. Hum Reprod. 2022;37(Suppl 1):deac106.078. [Google Scholar]
  • 21.Elguero S, Patel B, Forman M, Goldfarb J. Clinical characteristics associated with adherence to American Society of Reproductive Medicine (ASRM) embryo transfer (ET) guidelines. Fertil Steril. 2014;101:e32–3. [Google Scholar]
  • 22.Kim MJ, Choi HW, Park SY, Song IO, Seo JT, et al. Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men. J Assist Reprod Genet. 2012;29:539–46. doi: 10.1007/s10815-012-9748-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Dada R, Gupta NP, Kucheria K. Molecular screening for Yq microdeletion in men with idiopathic oligozoospermia and azoospermia. J Biosci. 2003;28:163–8. doi: 10.1007/BF02706215. [DOI] [PubMed] [Google Scholar]
  • 24.Zhang F, Li L, Wang L, Yang L, Liang Z, et al. Clinical characteristics and treatment of azoospermia and severe oligospermia patients with Y-chromosome microdeletions. Mol Reprod Dev. 2013;80:908–15. doi: 10.1002/mrd.22226. [DOI] [PubMed] [Google Scholar]
  • 25.Lange J, Skaletsky H, Bell GW, Page DC. MSY breakpoint mapper, a database of sequence-tagged sites useful in defining naturally occurring deletions in the human Y chromosome. Nucleic Acids Res. 2007;36:D809–14. doi: 10.1093/nar/gkm849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Alimardanian L, Saliminejad K, Razi S, Ahani A. Analysis of partial azoospermia factor c deletion and DAZ copy number in azoospermia and severe oligozoospermia. Andrologia. 2016;48:890–4. doi: 10.1111/and.12527. [DOI] [PubMed] [Google Scholar]
  • 27.Liu W, Gao X, Ma G, Yan L, Chen, et al. Correlation of genetic results with testicular histology, hormones and sperm retrieval in nonobstructive azoospermia patients with testis biopsy. Andrologia. 2016;49:e12705. doi: 10.1111/and.12705. [DOI] [PubMed] [Google Scholar]
  • 28.Dong Y, Du RC, Jiang YT, Wu J, Li LL, et al. Impact of chromosomal translocations on male infertility, semen quality, testicular volume and reproductive hormone levels. J Int Med Res. 2012;40:2274–83. doi: 10.1177/030006051204000625. [DOI] [PubMed] [Google Scholar]
  • 29.Yu XW, Wei ZT, Jiang YT, Zhang SL. Y chromosome azoospermia factor region microdeletions and transmission characteristics in azoospermic and severe oligozoospermic patients. Int J Clin Exp Med. 2015;8:14634–46. [PMC free article] [PubMed] [Google Scholar]
  • 30.Vijesh VV, Nambiar V, Mohammed SI, Sukumaran S, Suganthi R. Screening for AZFc partial deletions in Dravidian men with nonobstructive azoospermia and oligozoospermia. Genet Test Mol Biomarkers. 2015;19:150–5. doi: 10.1089/gtmb.2014.0251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Tyler-Smith C. An evolutionary perspective on Y-chromosomal variation and male infertility. Int J Androl. 2008;31:376–82. doi: 10.1111/j.1365-2605.2008.00889.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Dai RL, Sun LK, Yang X, Li LL, Zhu HB, et al. Expansion and de novo occurrence of Y chromosome microdeletions occurring via natural vertical transmission in Northeastern China. J Int Med Res. 2012;40:1182–91. doi: 10.1177/147323001204000339. [DOI] [PubMed] [Google Scholar]
  • 33.Reijo R, Alagappan RK, Patrizio P, Page DC. Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet. 1996;347:1290–3. doi: 10.1016/s0140-6736(96)90938-1. [DOI] [PubMed] [Google Scholar]
  • 34.Dada R, Kumar R, Shamsi MB, Kumar R, Kucheria K, et al. Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood. Asian J Androl. 2007;9:720–2. doi: 10.1111/j.1745-7262.2007.00274.x. [DOI] [PubMed] [Google Scholar]
  • 35.Martínez MC, Bernabé MJ, Gómez E, Ballesteros A, Landeras J, et al. Screening for AZF deletion in a large series of severely impaired spermatogenesis patients. J Androl. 2000;21:651–5. [PubMed] [Google Scholar]
  • 36.Kent-First MG, Kol S, Muallem A, Ofir R, Manor D, et al. The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers. Mol Hum Reprod. 1996;2:943–50. doi: 10.1093/molehr/2.12.943. [DOI] [PubMed] [Google Scholar]
  • 37.Liu XH, Yan LY, Lu CL, Li R, Zhu XH, et al. ART do not increase the risk of Y-chromosome microdeletion in 19 candidate genes at AZF regions. Reprod Fertil Dev. 2014;26:778–86. doi: 10.1071/RD13092. [DOI] [PubMed] [Google Scholar]
  • 38.Zhu Y, Wu T, Li G, Yin B, Liu H, et al. The sperm quality and clinical outcomes were not affected by sY152 deletion in Y chromosome for oligozoospermia or azoospermia men after ICSI treatment. Gene. 2015;573:233–8. doi: 10.1016/j.gene.2015.07.051. [DOI] [PubMed] [Google Scholar]
  • 39.Stouffs K, Vloeberghs V, Gheldof A, Tournaye H, Seneca S. Are AZFb deletions always incompatible with sperm production?Andrology . 2017;5:691–4. doi: 10.1111/andr.12350. [DOI] [PubMed] [Google Scholar]

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