Bjog-An International Journal of Obstetrics and Gynaecology最新文献

Objective: To examine the associations of antenatal corticosteroid (ACS) exposure with neurodevelopment in early childhood, and how these vary with gestational age at birth.

Design: Population-based cohort study.

Setting: Scotland, UK.

Population: 285 637 singleton children born at 28-41 weeks' gestation, between 1st January 2011 and 31st December 2017, who underwent health reviews at 27-30 months of age.

Methods: Logistic and linear regression analyses, stratified by gestation at birth (28-33, 34-36, 37-38 and 39-41 weeks' gestation), were used to evaluate the associations between ACS exposure and neurodevelopmental outcomes, and adjusted for maternal age, body mass index, diabetes, antenatal smoking, parity, neighbourhood deprivation, birth year, child sex and age at review.

Main outcome measures: Practitioner-identified concerns about any neurodevelopmental domain, and the average of five domain scores on neurodevelopmental milestones from the parent-rated Ages and Stages Questionnaire (ASQ-3).

Results: After adjustment for covariates, ACS exposure was associated with reduced neurodevelopmental concerns in children born at 28-33 weeks' gestation (OR = 0.79, 95% CI = 0.62-0.999) and with increased neurodevelopmental concerns in children born at 34-36 weeks' gestation (OR = 1.11, 95% CI = 1.01-1.21). No independent associations emerged in children born at later gestations. ACS exposure was not associated with ASQ-3 scores in any gestational age group.

Conclusions: In early childhood, ACS exposure was associated with statistically significantly reduced neurodevelopmental concerns in children born at 28-33 weeks' gestation, and with statistically significantly increased neurodevelopment concerns in children born at 34-36 weeks' gestation. However, the effect sizes of these associations were small. No independent associations were found between ACS exposure and neurodevelopment in term-born children.

Objective: To clarify the protective effects of gonadotropin-releasing hormone analogues (GnRHas) on cyclophosphamide (CTX)-induced oocyte number loss and development of potential damage.

Design: Mice model study.

Setting: Laboratory-based animal study conducted in controlled research facilities.

Population: Female C57/BL6 mice subjected to CTX-induced ovarian damage.

Methods: The effects of GnRHa on CTX mice were evaluated in terms of hormones, oocyte count on slices, oocyte count in established three-dimensional-constructed ovaries, in vitro fertilisation, RNA sequencing and microinjection.

Main outcome measures: The main outcome measures were the number of oocytes in intact mouse ovaries and oocyte quality, evaluated using three-dimensional (3D) tissue-clearing methods, oxidative stress markers (reactive oxygen species [ROS] and malondialdehyde [MDT]), mitochondrial function (ATP levels), and embryogenesis rates at the two-cell, four-cell and blastocyst stages.

Results: In CTX mice, GnRHa pretreatment did not protect endocrine hormone changes, but protected loss of oocyte number on slice counting. A tissue-clearing technique, CUBIC (Clear, Unobstructed Body Imaging Cocktails), was a suitable method for ovaries clearing, and a 3D method for oocyte counting was validated with accuracy of 105.22% ± 3.48%. By this method, GnRHa was also found to protect the loss of oocyte number (597 ± 28 vs. 222 ± 15, p < 0.0001), which may be mediated by upregulated anti-Müllerian hormone (AMH) levels inhibiting primordial follicle development approved by in vitro culture of ovaries. GnRHa also increased the number of retrieved oocytes in CTX mice (19.4 ± 2.1 vs. 15.0 ± 1.6, p < 0.0001) and developmental ability of oocytes (65.0 ± 4.6 vs. 48.1 ± 4.2 for blastocyst, p < 0.0001). RNA sequencing revealed GnRHa pretreatment downregulated pathways of exogenous drug metabolism, oxidative stress and cytochrome P450, validated by detection of adenosine triphosphate (ATP), MDA and ROS levels. The up-expression of Cox17 (cytochrome c oxidase copper chaperone 17) after GnRHa pretreatment was confirmed by PCR and microinjection of siCox17 increased the embryogenesis from CTX mice.

Conclusions: GnRHa was associated with reduced oocyte loss and improved embryogenesis, likely mediated by AMH and Cox17 upregulation.