Gene variants identified by whole-exome sequencing in 33 French women with premature ovarian insufficiency.

Purpose: To investigate the potential genetic etiology of premature ovarian insufficiency (POI).

Methods: Whole-exome sequencing (WES) was done on DNA samples from women diagnosed with POI. Mutations identified were analyzed by in silico tools and were annotated according to the guidelines of the American College of Medical Genetics and Genomics.

Genetics of Reproductive Aging from Gonadal Dysgenesis through Menopause.

Reproduction is essential for the survival of the species and is influenced by external factors such as smoking and exposure to chemotherapy as well as chronic disorders such as obesity and autoimmunity. Reproductive senescence, such as menopause, is also dependent on multiple intrinsic genetic factors. Reproductive aging is not isolated from an overall aging process, and several studies strongly support the link between the early age of menopause and mortality.

MCM8 and MCM9 Nucleotide Variants in Women With Primary Ovarian Insufficiency.

Objective: To assess the frequency of variants, including biallelic pathogenic variants, in minichromosome maintenance 8 (MCM8) and minichromosome maintenance 9 (MCM9), other genes related to MCM8-MCM9, and DNA damage repair (DDR) pathway in participants with primary ovarian insufficiency (POI).

Design: MCM8, MCM9, and genes encoding DDR proteins that have been implicated in reproductive aging were sequenced among POI participants.

Setting: Academic research institution.

The rs10993994 in the proximal MSMB promoter region is a functional polymorphism in Asian Indian subjects.

Background: The microseminoprotein gene encoding prostate secretory protein of 94 amino acids (PSP94) harbours a potential risk allele (rs10993994) for prostate cancer (PCa) in its promoter region. However, studies on rs10993994 have been sparse in Asian Indians.

Methods: The present study recruited a sample population of 44 benign prostatic hyperplasia patients, 33 PCa patients and 60 healthy participants, of which, participants without other confounding risk factors for PCa were retained.

Functional characterization of two naturally occurring mutations (Val514Ala and Ala575Val) in follicle-stimulating hormone receptor.

Context: Inactivating mutations have been reported in subjects with primary/secondary amenorrhea, whereas activating mutations are rare and seen only in women with ovarian hyperstimulation syndrome (OHSS). In the present study, we describe the functional characterization of the two mutations Val(514)Ala (novel mutation) and Ala(575)Val in FSH receptor (FSHR) identified in women with OHSS developed during in vitro fertilization and primary amenorrhea, respectively.

Objective: The objective of the investigation was to study the effect of mutations (514 and 575) on FSHR activity by in vitro functional studies.

Development of an ELISA for sPSP94 and utility of the sPSP94/sPSA ratio as a diagnostic indicator to differentiate between benign prostatic hyperplasia and prostate cancer.

Background: The serum PSA (sPSA) test has low specificity for prostate cancer (PCa), since sPSA also rises in benign prostatic hyperplasia (BPH). Serum PSP94 (sPSP94), a major secreted prostate protein, is indicated as a PCa marker. The potential of sPSP94 and sPSA in conjunction with each other to improve specificity of diagnostic test for PCa needs to be evaluated.

Mutations and polymorphisms in FSH receptor: functional implications in human reproduction.

FSH brings about its physiological actions by activating a specific receptor located on target cells. Normal functioning of the FSH receptor (FSHR) is crucial for follicular development and estradiol production in females and for the regulation of Sertoli cell function and spermatogenesis in males. In the last two decades, the number of inactivating and activating mutations, single nucleotide polymorphisms, and spliced variants of FSHR gene has been identified in selected infertile cases.

Association of allelic combinations of FSHR gene polymorphisms with ovarian response.

During an IVF protocol, exogenous FSH is administered to women for ovulation induction. The ovarian response to gonadotrophin stimulation is variable and unpredictable in these women. The FSHR is the most studied gene in relation to ovarian response.

Follicle-stimulating hormone receptor polymorphism (G-29A) is associated with altered level of receptor expression in Granulosa cells.

Context: Polymorphisms of the FSHR gene are associated with variable ovarian response to FSH stimulation in subjects undergoing in vitro fertilization (IVF) treatment. The type of ovarian response is correlated with the level of FSH receptor (FSHR) expression on granulosa cells.

Objective: We investigated whether the polymorphism at position -29 in the promoter of the FSHR gene may contribute in altered receptor expression.