A recent study reports that altered homeobox A10 (HOXA10) gene expression in the mid-secretory endometrium could play a role in infertility associated with endometriosis and uterine fibroids, as well as unexplained infertility. The findings, published in the recent issue of the journal Human Reproduction, suggest that the gene could be a potential target for new generation infertility treatments.

Sachiko Matsuzaki from CHU Clermont-Ferrand, Gynécologie Obstétrique et Médecine de la Reproduction, France, and co-workers, evaluated the expression levels of HOXA10 mRNA and protein in the endometrium of infertile patients with endometriosis and uterine fibroids, those with unexplained infertility, and fertile women (controls), during the mid-secretory phase of the endometrial development. Molecular techniques such as real time polymerase chain reaction (RT-PCR), laser capture microdissection, and immunohistochemistry were utilized in the study.

It was observed that the expression levels of HOXA10 mRNA and protein in the endometrial stromal cells were considerably lower in patients with various types of endometriosis (ovarian, superficial-peritoneal and deep infiltrating endometriosis), unexplained infertility and uterine myoma, when compared to the healthy controls. The expression level of HOXA10 mRNA was found to be lower in microdissected glandular epithelial cells compared to microdissected stromal cells, with the non-expression of the protein in the former group of cells. A considerably higher percentage of patients with superficial peritoneal endometriosis showed altered HOXA10 protein expression levels compared to the other groups. The study findings are listed in the table below:

The above results suggest that aberrant HOXA10 expression in the endometrial stromal cells during the implantation period could be one of the possible molecular pathologies of infertility, especially in superficial peritoneal endometriosis.

An earlier study by Li et al (Zhonghua Fu Chan Ke Za Zhi, 2002) showed that the expression level of HOXA10 mRNA was found to be higher during the mid- and late-secretory phases of the menstrual cycle in fertile women compared to patients with unexplained infertility. Based on these findings, the researchers suggested the following:
• Increased HOXA10 gene expression during the mid- and late-secretory phases signifies the role of the gene in implantation
• Abnormal HOXA10 expression could probably contribute to the etiology of unexplained infertility due to altered endometrium development at the molecular level
• HOXA10 gene could be involved in the decidualization of endometrium in early pregnancy

The HOXA10 gene, coding for an endometrial transcription factor, is essential for uterine development and function. The expression of this gene, driven by estrogen and progesterone, is suggested to be an essential regulator of endometrial development and embryo implantation.

The recent findings, demonstrating lower endometrial expression of HOXA10 in infertile patients during the window of implantation, emphasize the crucial role the gene plays in implantation and its importance in pregnancy. The expression of the gene product in the endometrial epithelium or stromal cells could thereby serve as a potential marker of uterine receptivity, and also aid in the investigation of other genes that are vital for establishing a successful pregnancy.

References

1. Matsuzaki S, Canis M, Darcha C, Pouly JL, Mage G. HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility. Hum Reprod. 2009 Sep 7. [Epub ahead of print]

2. Li H, Chen S, Xing F. Expression of HOXA10 gene in human endometrium and its relationship with unexplained infertility [in Chinese]. Zhonghua Fu Chan Ke Za Zhi. 2002 Jan;37(1):30-2.