Dysregulated expression of GATA2 and GATA6 transcription factors in adenomyosis: implications for impaired endometrial receptivity.

OBJECTIVE: To study the effect of adenomyosis on the localized expression of the GATA binding proteins 2 and 6 (GATA2 and GATA6) zinc-finger transcription factors that are involved in proliferation of hematopoietic and endocrine cell lineages, cell differentiation, and organogenesis, potentially leading to impaired endometrial implantation. DESIGN: Laboratory based experimental study. SETTING: Academic hospital and laboratory. PATIENTS: Human endometrial stromal cells (HESCs) of reproductive age patients, 18-45 years of age, with adenomyosis were compared with patients with no pathology and leiomyomatous uteri as controls (n = 4 in each group, respectively). Additionally, midsecretory phase endometrial sections were obtained from patients with adenomyosis and control patients with leiomyoma (n = 8 in each group, respectively). INTERVENTIONS: GATA2 and GATA6 immunohistochemistry and H-SCORE were performed on the midsecretory phase endometrial sections from adenomyosis and leiomyoma control patients (n = 8 each, respectively). Control and adenomyosis patient HESC cultures were treated with placebo or 10-8 M estradiol (E2), or decidualization media (EMC) containing 10-8 M E2, 10-7 M medroxyprogesterone acetate, and 5 × 10-5 M cAMP for 6 and 10 days. Additionally, control HESC cultures (n = 4) were transfected with scrambled small interfering RNA (siRNA) (control) or GATA2-specific siRNAs for 6 days while adenomyosis HESC cultures (n = 4) were transfected with human GATA2 expression vectors to silence or induce GATA2 overexpression. MAIN OUTCOME MEASURES: Immunohistochemistry was performed to obtain GATA2 and GATA6 H-SCORES in adenomyosis vs. control patient endometrial tissue. Expression of GATA2, GATA6, insulin-like growth factor-binding protein 1 (IGFBP1), prolactin (PRL), progesterone receptor (PGR), estrogen receptor 1 (ESR1), leukemia inhibitory factor (LIF), and Interleukin receptor 11 (IL11R) messenger RNA (mRNA) levels were analyzed using by qPCR with normalization to ACTB. Silencing and overexpression experiments also had the corresponding mRNA levels of the above factors analyzed. Western blot analysis was performed on isolated proteins from transfection experiments. RESULTS: Immunohistochemistry revealed an overall fourfold lower GATA2 and fourfold higher GATA6 H-SCORE level in the endometrial stromal cells of patients with adenomyosis vs. controls. Decidual induction with EMC resulted in significantly lower GATA2, PGR, PRL and IGFBP1 mRNA levels in HESC cultures from patients with adenomyosis patient vs. controls. Leukemia inhibitory factor and IL11R mRNA levels were also significantly dysregulated in adenomyosis HESCs compared with controls. . Silencing of GATA2 expression in control HESCs induced an adenomyosis-like state with significant reductions in GATA2, increases in GATA6 and accompanying aberrations in PGR, PRL, ESR1 and LIF levels. Conversely, GATA2 overexpression via vector in adenomyosis HESCs caused partial restoration of the defective decidual response with significant increases in GATA2, PGR, PRL and LIF expression. CONCLUSION: In-vivo and in-vitro experiment results demonstrate that there is an overall inverse relationship between endometrial GATA2 and GATA6 levels in patients with adenomyosis who have diminished GATA2 levels and concurrently elevated GATA6 levels. Additionally, lower GATA2 and higher GATA6 levels, together with aberrant levels of important receptors and implantation factors, such as ESR1, PGR, IGFBP1, PRL, LIF, and IL11R mRNA in HESCs from patients with adenomyosis or GATA2-silenced control HESCs, support impaired decidualization. These effects were partially restored with GATA2 overexpression in adenomyosis HESCs, demonstrating a potential therapeutic target.

Laparoscopic metroplasty: reconstructive surgery for unicornuate uterus with noncommunicating, functional uterine horn.

OBJECTIVE: To demonstrate laparoscopic surgery for a patient with unicornuate uterus and a large hematometra in the noncommunicating uterine horn. DESIGN: Narrated video featuring the diagnostic tests and surgical management. SETTING: Academic tertiary hospital. PATIENT(S): A 13-year-old woman, gravida 0 with menarche at 9 years old, had severe dysmenorrhea during her recent menstrual cycles. The results of transrectal three-dimensional sonography, hysteroscopy, and magnetic resonance imaging (MRI) were consistent for a uterine didelphys composed of a right unicornuate uterus and a left hemiuterus with hematometra and no connection to the cervix. Left adnexal endometrioma and ipsilateral renal agenesis were also noted. INTERVENTION(S): Laparoscopic adhesiolysis and enucleation of the left ovarian endometrioma were first performed. Then, implementing the concepts of Strassman unification method, a horizontal incision was made on the medial side of each hemicorpus, starting from the left rudimentary horn and ending at the fundal area of the right hemiuterus. The incision was carried deep enough to reach the endometrium. The opposing, reverted myometrium was then reapproximated from the lower end of the uterus to the upper fundal part in two layers, using absorbable bidirectional monofilament barbed suture. The outer serosal layer was closed with 1-0 Monocryl via a running continuous suture. On postoperative day 2, the patient was discharged uneventfully. MAIN OUTCOME MEASURE(S): Symptomatic relief and restoration of normal and functional anatomy. RESULT(S): The patient has regular menstrual cycles with no recurrence of dysmenorrhea or ovarian endometrioma. At a 2-year postoperative follow-up evaluation, hysteroscopic examination revealed a single uterine cavity with a small fundal septum. The MRI scans showed an anteverted, symmetrical uterus. CONCLUSION(S): In comparison with the widely applied hemihysterectomy, reconstructive laparoscopic metroplasty not only effectively achieves symptomatic relief but also offers better uterine symmetry and a larger intrauterine cavity via unification of the uterus.