Fetal Ovarian Reserve: the Dynamic Changes in Ubiquitin C-Terminal Hydrolase L1.

The regulation of protein turnover by the unique deubiquitinating enzyme ubiquitin C-terminal hydrolase L1 (UCHL1) is only seen in oocytes, spermatogonia, and neurons. Our objective was to investigate variation in expression of UCHL1 across fetal maturation of oocytes that result in lifelong ovarian reserve. We performed a retrospective cohort study of 25 fetal autopsy specimens from 21 to 36 weeks. This was an IRB-approved protocol with parental permission for use of tissues for research purposes. Tissues were stained for expression of the oocyte-specific protein UCHL1, and expression levels were evaluated using quantitative immunofluorescence across gestational ages after correction for the area and background absorbance. Corrected total cell fluorescence (CTCF) for expression of UCHL1 within human oocytes was compared across fetal gestational ages and oocyte size. Trends were analyzed using a locally weighted scatterplot smoothing algorithm. Local expression of UCHL1 increases in oocytes across ovarian development reaching a plateau at 27 weeks with the maintenance of elevated levels through 36 weeks gestational age. This maturation trend is also evidenced by the increase in protein expression as oocyte area increases (r = 0.5530, p ≤ 0.001) with the largest rise occurring as oocytes are enveloped into primordial follicles. The increase in expression as oocytes transition from oogonia into oocytes in primordial follicles and beyond may be part of the preparation of both oocytes and the surrounding somatic cells for the long-term maintenance of the ovarian reserve.

The requirement of ubiquitin C-terminal hydrolase L1 in mouse ovarian development and fertility†.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme enriched in neuronal and gonadal tissues known to regulate the cellular stores of mono-ubiquitin and protein turnover. While its function in maintaining proper motor neuron function is well established, investigation into its role in the health and function of reproductive processes is only just beginning to be studied. Single-cell-sequencing analysis of all ovarian cells from the murine perinatal period revealed that Uchl1 is very highly expressed in the developing oocyte population, an observation which was corroborated by high levels of oocyte-enriched UCHL1 protein expression in oocytes of all stages throughout the mouse reproductive lifespan. To better understand the role UCHL1 may be playing in oocytes, we utilized a UCHL1-deficient mouse line, finding reduced number of litters, reduced litter sizes, altered folliculogenesis, morphologically abnormal oocytes, disrupted estrous cyclicity and apparent endocrine dysfunction in these animals compared to their wild-type and heterozygous littermates. These data reveal a novel role of UCHL1 in female fertility as well as overall ovarian function, and suggest a potentially essential role for the ubiquitin proteasome pathway in mediating reproductive health.

A Systematic Review and Meta-analysis of Surgical Treatment of Ectopic Pregnancy with Salpingectomy versus Salpingostomy.

OBJECTIVE: To evaluate the fertility outcomes of salpingectomy compared with those of salpingostomy among patients treated for tubal ectopic pregnancies, including a separate analysis of women with risk factors along with a review of the surgical technique. DATA SOURCES: Systematic review and meta-analysis from 1990 to the present through PubMed, Embase, CINAHL, and Ovid MEDLINE. The search string included "tubal pregnancy" or "ectopic" as well as "salpingectomy" and various terms describing salpingotomy. METHODS OF STUDY SELECTION: Articles studying women who underwent surgical management of an ectopic pregnancy and the contrasted outcomes of salpingectomy vs salpingostomy were reviewed. The primary outcomes included subsequent intrauterine pregnancy (IUP) and repeat ectopic pregnancy (REP). TABULATION, INTEGRATION, AND RESULTS: Two randomized controlled trials (RCTs), which consisted mostly of patients classified as low risk, and patients from 16 cohort studies were included. In the RCTs, there was no significant difference in the odds of subsequent IUP in patients who underwent a salpingectomy compared with those who were treated with salpingotomy (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.71-1.33). However, a significant and clinically meaningful difference was noted in the cohort studies, with the patients having a lower chance of IUP after salpingectomy (OR 0.45; 95% CI, 0.39-0.52). No significant difference was noted in the OR for a REP in the randomized trials (OR 0.77; 95% CI, 0.41-1.47), but the patients followed in the cohort studies had a cumulatively higher risk of REP after a salpingostomy (OR 0.73; 95% CI, 0.60-0.90). The subgroup analysis examining women within the studies with risk factors for tubal pathology found an even more impressive lowering in the odds of a subsequent IUP in patients classified as at-risk who were treated with salpingectomy (OR 0.30; 95% CI, 0.17-0.54), with a change in the direction of the odds for an REP rate favoring those who were treated with salpingostomy (OR 1.96; 95% CI, 0.88-4.35). CONCLUSION: Salpingectomy has clear advantages over salpingostomy, and RCTs consisting mainly of patients classified as low risk show no difference in outcomes between salpingectomy and salpingostomy. However, in cohort studies inclusive of all patients, the likelihood of a subsequent spontaneous IUP is decreased in patients treated with salpingectomy, and salpingostomies may be especially underused in women with risk factors for tubal disease.