Follicle-stimulating hormone receptor (FSHR) is exclusively expressed in Sertoli cells within the testis. Mediated by FSHR, follicle-stimulating hormone (FSH) stimulates the proliferation and maturation of immature Sertoli cells via the cAMP/PKA, mTORC1 and AMPK signaling pathways. Simultaneously, FSH and androgen collaboratively regulate spermatogenesis in a synergistic manner. Given these physiological mechanisms, mutations in the FSHβ subunit frequently result in azoospermia; activating mutations in FSHR enable spermatogenesis to bypass FSH restrictions; while inactivating mutations in FSHR can impair male spermatogenesis. The association between FSHR single nucleotide polymorphisms and male infertility is influenced by gene locus and ethnicity, leading to inconsistent conclusions. This article highlights the profound significance of FSHR modulators for future infertility diagnosis and treatment, while also presenting a potential new avenue for male contraception.

Follicle-stimulating hormone receptor (FSHR) is exclusively expressed in Sertoli cells within the testis. Mediated by FSHR, follicle-stimulating hormone (FSH) stimulates the proliferation and maturation of immature Sertoli cells via the cAMP/PKA, mTORC1 and AMPK signaling pathways. Simultaneously, FSH and androgen collaboratively regulate spermatogenesis in a synergistic manner. Given these physiological mechanisms, mutations in the FSHβ subunit frequently result in azoospermia; activating mutations in FSHR enable spermatogenesis to bypass FSH restrictions; while inactivating mutations in FSHR can impair male spermatogenesis. The association between FSHR single nucleotide polymorphisms and male infertility is influenced by gene locus and ethnicity, leading to inconsistent conclusions. This article highlights the profound significance of FSHR modulators for future infertility diagnosis and treatment, while also presenting a potential new avenue for male contraception.

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

The energy consumed by oocyte maturation is partly derived from cumulus cells, but is mainly produced by oocyte mitochondria; the substrate for energy metabolism is glucose, followed by lipid and amino acids. Glucose can be metabolized by four pathways, namely glycolytic pathway, pentose phosphate pathway, hexosamine biosynthetic pathway and polyol pathway. The glycolytic pathway is one of the main metabolic pathways, but its efficiency is low when it is anaerobic or hypoxic. When it is aerobic, oocytes mainly metabolize glucose through the oxidative phosphorylation pathway of mitochondria.This paper reviews the role of glucose metabolism in oocyte maturation and the synchronization of oocyte nuclear and cytoplasmic maturation. It is expected to optimize the protocol of oocyte in vitro maturation by regulating glucose metabolism, which is beneficial to improve the quality and development potential of in vitromaturation oocyte.

Patients with endometriosis are often associated with follicular growth retardation and oocyte maturation disorders, severely affecting patient fertility. In patients with endometriosis, the occurrence of apoptosis and oxidative stress events in granulosa cells, impaired cellular energy metabolism and steroid synthesis in patients with endometriosis may be the cause of abnormal follicular development and decreased oocyte quality. The inflammatory response caused by endometrioma, which afterwards leads excessive activation of follicles and fibrosis of the ovarian cortex, which directly reduces ovarian reserve. This article discusses the oxidative stress and apoptosis of follicle granulosa cells, steroid hormone synthesis, energy metabolism abnormality in patients with endometriosis, and explains the adverse effects of endometrioma on ovarian reserve from the perspective of inflammatory response.

The energy consumed by oocyte maturation is partly derived from cumulus cells, but is mainly produced by oocyte mitochondria; the substrate for energy metabolism is glucose, followed by lipid and amino acids. Glucose can be metabolized by four pathways, namely glycolytic pathway, pentose phosphate pathway, hexosamine biosynthetic pathway and polyol pathway. The glycolytic pathway is one of the main metabolic pathways, but its efficiency is low when it is anaerobic or hypoxic. When it is aerobic, oocytes mainly metabolize glucose through the oxidative phosphorylation pathway of mitochondria.This paper reviews the role of glucose metabolism in oocyte maturation and the synchronization of oocyte nuclear and cytoplasmic maturation. It is expected to optimize the protocol of oocyte in vitro maturation by regulating glucose metabolism, which is beneficial to improve the quality and development potential of in vitromaturation oocyte.

Patients with endometriosis are often associated with follicular growth retardation and oocyte maturation disorders, severely affecting patient fertility. In patients with endometriosis, the occurrence of apoptosis and oxidative stress events in granulosa cells, impaired cellular energy metabolism and steroid synthesis in patients with endometriosis may be the cause of abnormal follicular development and decreased oocyte quality. The inflammatory response caused by endometrioma, which afterwards leads excessive activation of follicles and fibrosis of the ovarian cortex, which directly reduces ovarian reserve. This article discusses the oxidative stress and apoptosis of follicle granulosa cells, steroid hormone synthesis, energy metabolism abnormality in patients with endometriosis, and explains the adverse effects of endometrioma on ovarian reserve from the perspective of inflammatory response.

OBJECTIVE To investigate the correlation of 21-hydroxylase deficiency (21-OHD) with male testicular dysplasia. METHODS Clinical data of 8 infertile males with congenital adrenal hyperplasia due to 21-OHD was retrospectively analyzed. In addition, potential mutations of the CYP21A2 gene was detected. RESULTS All patients were referred because of azoospermia or severe oligospermia and had small testis with averaged testicular volume of 6.1 mL. Three patients had testicular adrenal rest tumors. Endocrinologic examinations revealed low levels of leutinizing hormone and follicular stimulating hormone, normal or elevated testosterone, elevated progesterone, elevated or normal adrenocoticotropic hormone, and low or normal cortisol. All patients had adrenal cortical hyperplasia, 5 with adrenal adenoma, 1 case associated with bilateral adrenal myelolipoma. All patients were given glucocorticoid replacement therapy for 3 to 6 months, which successfully improved the seminal status of 6 patient and resulted pregnancies in 5 couples. Seven pathogenic mutations of the CYP21A2 gene among the 8 patients. CONCLUSION 21-OHD can cause testicular hypoplasia and spermatogenic failure. Glucocorticoids and operations can obtain good result and improve spermatogenesis. Our results have shown a good genotype/phenotype correlation in these cases. All patients have carried the p.Ile172Asn mutation, which is associated with simple virilizing form.

Objective Using of cumulative live birth rate(CLBR)per oocytes retrieved cycle,to assess the clinical outcomes of in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI),and to explore impact factors on CLBR following utilization of all fresh and frozen embryos in one complete IVF/ICSI cycle using gonadotropin-releasing hormone(GnRH)agonist, GnRH-antagonist and clomiphene mild stimulation protocols. Methods Of the patients who underwent IVF/ICSI from January 1st, 2014 to December 31st, 2015 in the First Affiliated Hospital, Nanjing Medical University, a total of 6 142 oocytes retrieved cycles were included. The clinical and laboratory parameters of different ovarian stimulation protocols, and the effects of the age, number of oocytes retrieved and number of embryos available on the CLBR of each oocytes retrieved cycle were analyzed.Results The CLBR was 69.0%(2 004/2 906)in the GnRH-agonist protocol versus 67.4%(644/955)in the GnRH-antagonist protocol (P>0.05); the CLBR of clomiphene mild stimulation protocol was 53.2%(1 215/2 281),significantly lower than those of the other two protocols (all P<0.05). The CLBR significantly decreased with age increased. When divided into four groups according to the patients′ age, we found that CLBR were not statistically significant using three different protocols in the 20-25 years old group(all P>0.05).There was a strong association between the number of oocytes retrieved and embryos available on CLBR. CLBR rose significantly with an increasing number of oocytes up to 6, then the rising trend slowed down. Patients were categorized into four groups according to the number of oocytes retrieved,CLBR was significantly higher using GnRH-antagonist protocol (50.0%)than mild stimulation protocol(37.0%)in low ovarian responder(0-4 oocytes)group(P<0.05). The CLBR were no significant difference among three protocols in normal(10-15 oocytes)and high responders(≥15 oocytes)group(all P>0.05).The incidence rate of ovarian hyperstimulation syndrome in GnRH-agonist protocols(5.2%,152/2 906)were significantly higher than those of GnRH-antagonist(4.4%, 42/955)and clomiphene mild stimulation protocols(1.5%,34/2 281;all P<0.05).Conclusions CLBR is an important index to assess the clinical outcomes of IVF/ICSI. Age, number of oocytes retrieved and embryos available could affect CLBR obviously. According to the different age and ovarian response of patients, we should design ovarian stimulation protocols based on target oocytes number in order to get higher CLBR and reduce complications.

Objective To evaluate the efficiency of the application of array comparative genomic hybridization (array-CGH) in preimplantation genetic diagnosis or screening (PGD/PGS), and compare the clinical outcomes of different stage embryo biopsy. Methods The outcomes of 381 PGD/PGS cycles referred in the First Affiliated Hospital of Nanjing Medical University from July 2011 to August 2015 were retrospectively analyzed. There were 320 PGD cycles with 156 cleavage-stage-biopsy cycles and 164 trophectoderm-biopsy cycles, 61 PGS cycles with 23 cleavage-stage-biopsy cycles and 38 trophectoderm-biopsy cycles.Chromosomal analysis was performed by array-CGH technology combined with whole genome amplification.Single embryo transfer was performed in all transfer cycles.Live birth rate was calculated as the main clinical outcomes. Results The embryo diagnosis rate of PGD/PGS by array-CGH were 96.9%-99.1%. In PGD biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were 50.0%(58/116) and 37.2%(58/156) in cleavage-stage-biopsy group, 67.5%(85/126) and 51.8%(85/164) in trophectoderm-biopsy group (both P<0.01). In PGS biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were the same as 34.8%(8/23) in cleavage-stage-biopsy group, the same as 42.1%(16/38) in trophectoderm-biopsy group (both P>0.05). Conclusions High diagnosis rate and idea live birth rate are achieved in PGD/PGS cycles based on array-CGH technology.The live birth rate of trophectoderm-biopsy group is significantly higher than that of cleavage-stage-biopsy group in PGD cycles;the efficiency of trophectoderm-biopsy is better.