1.Poorly-Controlled Type 1 Diabetes Mellitus Impairs LH-LHCGR Signaling in the Ovaries and Decreases Female Fertility in Mice
Jaewang LEE ; Hoi Chang LEE ; So Youn KIM ; Geum Joon CHO ; Teresa K WOODRUFF
Yonsei Medical Journal 2019;60(7):667-678
PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.
Animals
;
Anti-Mullerian Hormone
;
Biomarkers
;
Blood Glucose
;
Body Weight
;
Corpus Luteum
;
Diabetes Mellitus
;
Diabetes Mellitus, Type 1
;
Embryonic Development
;
Embryonic Structures
;
Enzyme-Linked Immunosorbent Assay
;
Estradiol
;
Female
;
Female
;
Fertility
;
Fertilization
;
Fertilization in Vitro
;
Gonadotropins
;
Humans
;
Immunohistochemistry
;
Lutein
;
Mental Competency
;
Metaphase
;
Mice
;
Oocytes
;
Oogenesis
;
Ovary
;
Pregnancy
;
Progesterone
;
Reproduction
;
Streptozocin
;
Testosterone
2.Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility.
Hui-Yu XU ; Hong-Xian ZHANG ; Zhen XIAO ; Jie QIAO ; Rong LI
Asian Journal of Andrology 2019;21(2):109-114
Anti-Müllerian hormone (AMH) is a functional marker of fetal Sertoli cells. The germ cell number in adults depends on the number of Sertoli cells produced during perinatal development. Recently, AMH has received increasing attention in research of disorders related to male fertility. This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders. We have determined that follicle-stimulating hormone (FSH) promotes AMH transcription in the absence of androgen signaling. Testosterone inhibits the transcriptional activation of AMH. The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue, for example, that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis. The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Müllerian duct syndrome (PMDS), combined with clinical manifestations. The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development (DSD). Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells. Serum AMH levels are varying in patients with male fertility-related disorders, including pubertal delay, severe congenital hypogonadotropic hypogonadism, nonobstructive azoospermia, Klinefelter syndrome, varicocele, McCune-Albright syndrome, and male senescence.
Anti-Mullerian Hormone/metabolism*
;
Follicle Stimulating Hormone/blood*
;
Gene Expression Regulation
;
Humans
;
Infertility, Male/blood*
;
Male
;
Testosterone/blood*
3.Correlation of serum anti-Müllerian hormone with semen parameters.
Long-Ping PENG ; Yong SHAO ; Cen-Cen WANG ; Zhi-Chuan ZOU ; Tao SHEN ; Li CHEN ; Bing YAO
National Journal of Andrology 2017;23(6):531-535
Objective:
To investigate the relationship between the serum anti-Müllerian hormone (AMH) level and semen parameters.
METHODS:
We collected the data about 726 outpatients at the Male Infertility Clinic of Jinling Hospital from September 2015 to November 2016, including 72 with non-obstructive azoospermia, 123 with oligospermia, and 531 with normal sperm concentration. We obtained the semen volume, total sperm count, sperm concentration, sperm motility, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), and the levels of serum AMH, inhibin B (INH-B), total testosterone (TT) and follicle - stimulating hormone (FSH) of the patients, analyzed the correlation of the serum AMH level with the other parameters, and compared the AMH level among different groups.
RESULTS:
The serum AMH level was found to be correlated positively with the total sperm count (r = 0.227, P <0.001), sperm concentration (r = 0.215, P <0.001), sperm motility (r = 0.111, P = 0.003), the percentage of PMS (r = 0.120, P = 0.001), and the levels of INH-B (r = 0.399, P <0.001) and TT (r = 0.184, P = 0.002), negatively with the FSH level (r = -0.283, P <0.001), but insignificantly with age, time of abstinence, semen volume, and the percentage of MNS (P >0.05). There was a statistically significant difference in the serum AMH level among the patients with non-obstructive azoospermia, oligozoospermia, and normal sperm concentration ([6.33 ± 4.26] vs [8.26 ± 3.98] vs [9.8 ± 5.19] ng/ml, P <0.001).
CONCLUSIONS
Serum AMH is a biomarker reflecting the function of Sertoli cells and its level is significantly correlated with sperm concentration and motility, suggesting that AMH may be involved in spermatogenesis and sperm maturation.
Anti-Mullerian Hormone
;
blood
;
Azoospermia
;
blood
;
Biomarkers
;
blood
;
Follicle Stimulating Hormone
;
blood
;
Humans
;
Inhibins
;
blood
;
Male
;
Oligospermia
;
blood
;
Semen
;
Semen Analysis
;
Sertoli Cells
;
physiology
;
Sperm Count
;
Sperm Motility
;
Spermatogenesis
;
Spermatozoa
;
Testosterone
;
blood
4.Seminal plasma anti-Müllerian hormone and inhibin B and serum inhibin B in predicting the outcome of routine IVF fertilization.
Yan-Fei WANG ; Xin WU ; Rong HU ; Fei-Miao WANG ; Shao-Tong JIA ; Li-Guo PEI ; Hui WANG ; Xiao-E OUYANG ; Ting HU ; Yun-Xing FU
National Journal of Andrology 2017;23(11):991-996
Objective:
To analyze the correlations of seminal plasma (sp) anti-Müllerian hormone (spAMH) and inhibin B (spINHB) and serum INHB (serINHB) with semen parameters in oligoasthenospermia patients and explore their value in predicting the outcome of routine in vitro fertilization (IVF).
METHODS:
We obtained the levels of spAMH, spINHB and serINHB as well as semen parameters from 88 infertile males undergoing IVF due to oligoasthenospermia or female uterine tubal factors from August 2016 to February 2017. Using the ROC curve and Pearson's correlation analysis, we examined the effects of the obtained parameters on the fertilization rate and assessed the correlation of the levels of spAMH, spINHB and serINHB with the semen parameters of the patients.
RESULTS:
Concerning the predictive value for the outcome of IVF, Pearson's correlation analysis showed that the area under the ROC curve (AUC) of spAMH was 0.807 (sensitivity = 84.6%, specificity = 76%, cut-off point = 3.529, P <0.001) and that of spINHB was 0.768 (sensitivity = 84.6%, specificity = 88.7%, cut-off point = 31.117, P = 0.002). The serINHB level was found positively correlated with sperm concentration (r = 0.346, P = 0.001), total sperm count (r = 0.378, P <0.001), sperm motility (r = 0.521, P <0.001), and the percentage of progressively motile sperm (r = 0.343, P = 0.001).
CONCLUSIONS
The levels of spAMH and spINHB can be used as laboratory indexes to predict the fertilization rate of routine IVF and are correlated with semen parameters in oligoasthenospermia patients, while that of serINHB has a positive correlation with the semen parameters of the patients.
Anti-Mullerian Hormone
;
analysis
;
blood
;
Asthenozoospermia
;
Female
;
Fertilization
;
Fertilization in Vitro
;
Humans
;
Infertility, Female
;
Inhibins
;
analysis
;
blood
;
Male
;
Oligospermia
;
ROC Curve
;
Semen
;
chemistry
;
Sperm Count
;
Sperm Motility
5.Orchidopexy increases the levels of serum anti-Müllerian hormone and inhibin B in cryptorchidism patients.
Shun-Shun CAO ; Yang-Yang HU ; Cun-Jin NAN
National Journal of Andrology 2017;23(8):713-716
Objective:
To investigate the levels of serum anti-Müllerian hormone (AMH) and inhibin B (INHB) in patients with unilateral cryptorchidism before and after orchidopexy.
METHODS:
This study included 58 cases of unilateral cryptorchidism treated by orchidopexy and 32 healthy controls. Before and at 6 months after surgery, we measured the length and circumference of the penis, the volume of the undescended testis, and levels of serum AMH and INHB.
RESULTS:
There were statistically significant differences between the unilateral cryptorchidism and healthy control groups in the levels of serum AMH ([102.80 ± 17.35 vs 108.76 ± 13.64] ng/ml, P<0.05) and INHB ([70.24 ± 5.73] vs [ 77.72 ± 5.94] pg/ml, P<0.05) at the baseline, but not at 6 months after orchidopexy (AMH: [109.76 ± 17.25] vs [108.03 ± 14.13] ng/ml, P>0.05; INHB: [75.76 ± 5.94] vs [77.63 ± 5.99] pg/ml, P>0.05). No remarkable differences were observed between the unilateral cryptorchidism and healthy control groups in the preoperative penile length ([2.05 ± 0.23] vs [2.11 ± 0.22] cm, P>0.05), penile circumference ([3.91 ± 0.23] vs [3.99 ± 0.20] cm, P>0.05) and volume of the undescended testis ([0.45 ± 0.02] vs [0.46 ± 0.02] ml, P>0.05), or in the postoperative penile length ([2.09 ± 0.23] vs [2.16 ± 0.22] cm, P>0.05), penile circumference ([4.00 ± 0.25] vs [3.98 ± 0.19] cm, P>0.05) and volume of the undescended testis ([0.45 ± 0.02] vs [0.45 ± 0.02] ml, P>0.05). Compared with the baseline, the cryptorchidism patients showed markedly increased levels of serum AMH ([102.80 ± 17.35] vs [109.76 ± 17.25] ng/ml, P<0.05) and INHB ([70.24 ± 5.73] vs [75.76 ± 5.94] pg/ml, P<0.05) after orchidopexy.
CONCLUSIONS
Orchidopexy can elevate the levels of serum AMH and INHB and protect the testicular function of cryptorchidism patients.
Anti-Mullerian Hormone
;
blood
;
Case-Control Studies
;
Cryptorchidism
;
blood
;
pathology
;
surgery
;
Humans
;
Inhibins
;
blood
;
Male
;
Orchiopexy
;
Organ Size
;
Penis
;
anatomy & histology
;
Postoperative Period
;
Preoperative Period
6.Hydrogen-rich Water Exerting a Protective Effect on Ovarian Reserve Function in a Mouse Model of Immune Premature Ovarian Failure Induced by Zona Pellucida 3.
Xin HE ; Shu-Yu WANG ; Cheng-Hong YIN ; Tong WANG ; Chan-Wei JIA ; Yan-Min MA
Chinese Medical Journal 2016;129(19):2331-2337
BACKGROUNDPremature ovarian failure (POF) is a disease that affects female fertility but has few effective treatments. Ovarian reserve function plays an important role in female fertility. Recent studies have reported that hydrogen can protect male fertility. Therefore, we explored the potential protective effect of hydrogen-rich water on ovarian reserve function through a mouse immune POF model.
METHODSTo set up immune POF model, fifty female BALB/c mice were randomly divided into four groups: Control (mice consumed normal water, n = 10), hydrogen (mice consumed hydrogen-rich water, n = 10), model (mice were immunized with zona pellucida glycoprotein 3 [ZP3] and consumed normal water, n = 15), and model-hydrogen (mice were immunized with ZP3 and consumed hydrogen-rich water, n = 15) groups. After 5 weeks, mice were sacrificed. Serum anti-Müllerian hormone (AMH) levels, granulosa cell (GC) apoptotic index (AI), B-cell leukemia/lymphoma 2 (Bcl-2), and BCL2-associated X protein (Bax) expression were examined. Analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA) software.
RESULTSImmune POF model, model group exhibited markedly reduced serum AMH levels compared with those of the control group (5.41 ± 0.91 ng/ml vs. 16.23 ± 1.97 ng/ml, P = 0.033) and the hydrogen group (19.65 ± 7.82 ng/ml, P = 0.006). The model-hydrogen group displayed significantly higher AMH concentrations compared with that of the model group (15.03 ± 2.75 ng/ml vs. 5.41 ± 0.91 ng/ml, P = 0.021). The GC AI was significantly higher in the model group (21.30 ± 1.74%) than those in the control (7.06 ± 0.27%), hydrogen (5.17 ± 0.41%), and model-hydrogen groups (11.24 ± 0.58%) (all P < 0.001). The GC AI was significantly higher in the model-hydrogen group compared with that of the hydrogen group (11.24 ± 0.58% vs. 5.17 ± 0.41%, P = 0.021). Compared with those of the model group, ovarian tissue Bcl-2 levels increased (2.18 ± 0.30 vs. 3.01 ± 0.33, P = 0.045) and the Bax/Bcl-2 ratio decreased in the model-hydrogen group.
CONCLUSIONSHydrogen-rich water may improve serum AMH levels and reduce ovarian GC apoptosis in a mouse immune POF model induced by ZP3.
Animals ; Anti-Mullerian Hormone ; blood ; Apoptosis ; drug effects ; Female ; Granulosa Cells ; cytology ; Hydrogen ; chemistry ; pharmacology ; Mice ; Mice, Inbred BALB C ; Ovarian Reserve ; drug effects ; physiology ; Ovary ; drug effects ; metabolism ; Primary Ovarian Insufficiency ; blood ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Water ; administration & dosage ; chemistry ; pharmacology ; Zona Pellucida ; drug effects ; physiology ; bcl-2-Associated X Protein ; metabolism
7.Impact of unilateral cryptorchidism on the levels of serum anti-müllerian hormone and inhibin B.
Shun-Shun CAO ; Xiao-Ou SHAN ; Yang-Yang HU
National Journal of Andrology 2016;22(9):805-808
ObjectiveTo investigate the influence of unilateral cryptorchidism on the levels of serum anti-müllerian hormone (AMH) and inhibin B in children.
METHODSWe enrolled 65 patients with unilateral cryptorchidism and 45 healthy children in this study. We measured the length and circumference of the penis, the testis volume in the cryptorchidism side, and the levels of serum AMH and inhibin B at the age of 6 and 12 months, respectively.
RESULTSCompared with the healthy controls, the patients with unilateral cryptorchidism showed significant decreases at 12 months in serum AMH ([108.06±12.40] vs [103.26±17.57] ng/ml, P<0.05) and inhibin B ([77.43±5.66] vs [70.21±5.69] pg/ml, P<0.05). No statistically significant differences were found in the length and circumference of the penis and the testis volume in the cryptorchidism side at 6 and 12 months (P>0.05), or in the levels of serum AMH and inhibin B at 6 months (P>0.05).
CONCLUSIONSUnilateral cryptorchidism affects the gonadal function of the patient, and orchiopexy should be timely performed in order to reduce its impact.
Anti-Mullerian Hormone ; blood ; Case-Control Studies ; Cryptorchidism ; blood ; pathology ; Humans ; Infant ; Inhibins ; blood ; Male ; Orchiopexy ; Organ Size ; Penis ; pathology ; Testis ; pathology ; physiopathology ; Transforming Growth Factor beta
8.Correlation between the Serum Luteinizing Hormone to Folliclestimulating Hormone Ratio and the Anti-Mullerian Hormone Levels in Normo-ovulatory Women.
Jong Eun LEE ; Sang Ho YOON ; Hye Ok KIM ; Eung Gi MIN
Journal of Korean Medical Science 2015;30(3):296-300
Serum anti-Mullerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.
Adult
;
Aging/blood
;
Anti-Mullerian Hormone/*blood
;
Female
;
Follicle Stimulating Hormone/*blood
;
Humans
;
Luteinizing Hormone/*blood
;
Menstruation/blood/physiology
;
Middle Aged
;
Ovarian Reserve/*physiology
;
Ovulation/*blood/physiology
;
Retrospective Studies
;
Young Adult
9.Correlation between the Serum Luteinizing Hormone to Folliclestimulating Hormone Ratio and the Anti-Mullerian Hormone Levels in Normo-ovulatory Women.
Jong Eun LEE ; Sang Ho YOON ; Hye Ok KIM ; Eung Gi MIN
Journal of Korean Medical Science 2015;30(3):296-300
Serum anti-Mullerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.
Adult
;
Aging/blood
;
Anti-Mullerian Hormone/*blood
;
Female
;
Follicle Stimulating Hormone/*blood
;
Humans
;
Luteinizing Hormone/*blood
;
Menstruation/blood/physiology
;
Middle Aged
;
Ovarian Reserve/*physiology
;
Ovulation/*blood/physiology
;
Retrospective Studies
;
Young Adult
10.What Number of Oocytes Is Appropriate for Defining Poor Ovarian Response?.
Seul Ki KIM ; Jung Ryeol LEE ; Byung Chul JEE ; Chang Suk SUH ; Seok Hyun KIM
Yonsei Medical Journal 2015;56(2):482-489
PURPOSE: This study attempted to derive an objective and sophisticated definition of poor ovarian response (POR). MATERIALS AND METHODS: A total of 176 consecutive in vitro fertilization (IVF) cycles (137 patients) with conventional ovarian stimulation during 2009 to 2012 were studied by retrospective analysis. Optimal oocyte number (total or mature) was determined by statistics-based (distribution of oocyte number) and prognosis-based approaches (prediction for IVF outcome). Receiver operating characteristics curve analysis was used to show what number of oocytes could predict IVF pregnancy and whether clinical and laboratory variables could predict newly defined POR. RESULTS: The 25th percentile of the distribution corresponded to total oocytes < or =2 and mature oocyte < or =1. The cut-off values for the prediction of IVF outcomes were total oocytes >5 and mature oocyte >1. Considering the incidence of POR (34.1%), a reasonable definition of POR was decided as total oocytes < or =2 or mature oocyte < or =1. For the prediction of this new definition, the extreme cut-off value (by setting a false positive rate of 5%) of serum anti-Mullerian hormone (AMH) was < or =0.76 ng/mL, which was better than serum follicle stimulating hormone or age. A new simple definition of POR was derived as total oocytes < or =2 or mature oocyte < or =1 in a previous cycle or a serum AMH level of < or =0.76 ng/mL. When this simple criterion was re-applied to our data, the predictive performance was similar to the Bologna criteria. CONCLUSION: We here propose a new definition of POR, which is simple and supported by statistical and prognostic analyses.
Adult
;
Anti-Mullerian Hormone/blood
;
Female
;
Fertilization in Vitro
;
Follicle Stimulating Hormone/blood
;
Humans
;
Infertility, Female/blood/*therapy
;
*Oocytes
;
*Ovulation Induction
;
Pregnancy
;
Prognosis
;
ROC Curve
;
Retrospective Studies
;
*Sperm Injections, Intracytoplasmic
;
Treatment Outcome

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