Association between Estrogen Receptor-β Gene Polymorphisms and Ovulatory Dysfunctions in Patients with Menstrual Disorders

Abstract

Estrogen plays a significant role in human ovulation. It acts as an important positive regulator of the preovulatory gonadotropin surge necessary to initiate the cascade of events leading to ovulation. The steroid hormone exerts its physiological responses through the estrogen receptor (ER), of which two subtypes, ERalpha and ERbeta, are known. ERbeta messenger ribonucleic acid occurs maximally in the ovaries and granulosa cells; thus, ERbeta may be essential for normal ovulation. In a recent gene knockout study, it has been shown that ERbeta gene null female mice develop normal reproductive tract and ovaries during pre- and neonatal periods, but have an abnormal frequency of spontaneous ovulation in adulthood. In the present case-control study, we explored the association of two recently described ERbeta gene polymorphisms, RSAI and ALUI, with ovulatory dysfunctions. The respective frequencies of these polymorphisms were significantly higher in patients than in controls (P= 0.009 and P= 0.059). The polymorphisms were significantly associated with ovulatory dysfunctions, especially in patients homozygous for the polymorphisms (P = 0.016 and P = 0.038, respectively). The compound homozygosity of the polymorphisms was seen only in patients (n = 5) and not controls (P = 0.009). The serum levels of LH, FSH, and progesterone were lower in the homozygous and compound homozygous than in the respective nonpolymorphic patients. All five compound homozygous patients had ovulatory dysfunctions with no etiological pathology. Our results suggest that ERbeta gene RSA:I and ALU:I polymorphisms may be associated with ovulatory defects in some patients, especially those with unknown causes.

Estrogen Receptor Alpha and Beta Gene Polymorphisms Are Not Risk Factors for Recurrent Miscarriage in a Brazilian Population

“…[19][20][21] In contrast, the prevalence was different from that for an Asian population. 11,22 Our results highlight the importance of determining the prevalence of polymorphisms in the normal population, which can be variable depending on the ethnicity and the background of patients. When we compared the prevalence of ESR1 and ESR2 polymorphisms between RM patients with and without thrombophilia and controls, no differences were observed.…”

“…The first is located in the ligand-binding domain of exon 5 and the second in the 3′-untranslated region of exon 8, respectively. 11 Factor V:Q 506 , G20210A mutation in the prothrombin gene, and C677T in the MTHFR were screened as previously described. 14,15…”

“…Keywords: recurrent miscarriage; estrogen receptors; polymorphisms hormone, and progesterone in women with ovulatory dysfunctions. 11 Previous reports investigated the B region in the ESR1 gene in primary and secondary recurrent spontaneous abortion, 12 but no study has analyzed other polymorphisms in the ESR1 and ESR2 genes.…”

ERβ Regulation of Gonadotropin Responses during Folliculogenesis

“…ERβ is the predominant estrogen receptor in the ovary [143][144][145][146]. ERβ polymorphisms and mutations in women have been linked to ovulatory dysfunctions, including complete ovarian failure [147][148][149][150]. PCOS, a common clinical condition among women that causes failure of ovulation and infertility, is associated with high levels of LH and androgens [151,152].…”

The association of codon 392 polymorphism in ESR2 gene with breast cancer in Iran

“…Among German population Five SNPs in ER-β gene have been identified [14], however, only rs1256049, showed an association with anorexia nervosa. This SNP had shown colorations with ovulatory dysfunction in a Chinese and Brazilian [15], [16]. Moreover, a CA nucleotide repeats in ESR2 gene revealed association with bone density in Japanese.…”