Histologic analysis and lipid profiling reveal reproductive age-associated changes in peri-ovarian adipose tissue

Abstract

Background Reproductive aging is a robust phenotype that occurs in all females and is characterized by a significant reduction in gamete quantity and quality, which can have negative consequences on both endocrine function and fertility. Age-associated differences in the oocyte, follicle, and ovary have been well-documented, but how the broader environment changes with age is less well understood. Fat is one of the largest organs in the body, and peri-gonadal adipose tissue surrounds the rodent ovary and comprises a local ovarian environment. The goal of this study was to characterize how peri-ovarian adipose tissue changes with advanced reproductive age. Methods We isolated peri-gonadal adipose tissue from two cohorts of CB6F1 mice: reproductively young (6–12 weeks) and reproductively old (14–17 months). A comparative histological analysis was performed to evaluate adipocyte architecture. We then extracted lipids from the tissue and performed multiple reaction monitoring (MRM)-profiling, a mass spectrometry-based method of metabolite profiling, to compare the lipid profiles of peri-gonadal adipose tissue in these age cohorts. Results We found that advanced reproductive age was associated with adipocyte hypertrophy and a corresponding decrease in the number of adipocytes per area. Of the 10 lipid classes examined, triacylglycerols (TAGs) had significantly different profiles between young and old cohorts, despite quantitative analysis revealing a decrease in the total amount of TAGs per weight of peri-gonadal adipose tissue with age. Conclusions These findings pinpoint age-associated physiological changes in peri-gonadal adipose tissue with respect to adipocyte morphology and lipid profiles and lay the foundation for future studies to examine how these alterations may influence both adipocyte and ovarian function. Electronic supplementary material The online version of this article (10.1186/s12958-019-0487-6) contains supplementary material, which is available to authorized users.

Ovulation and ovarian wound healing are impaired with advanced reproductive age

“…The mice we used to represent advanced reproductive age were 14-17 months old, which based on a linear extrapolation estimate, corresponds to women 38-45 years old [21]. Furthermore, this specific mouse strain demonstrates many reproductive aging phenotypes including reduced ovarian reserve, increased egg aneuploidy, ovarian stromal fibrosis, and altered adiposity [15,[21][22][23]. We confirmed this model by performing follicle counts in mice following hyperstimulation and superovulation since reduced follicle numbers are a hallmark of reproductive aging [24].…”

Exacerbation of Nanoparticle-Induced Acute Pulmonary Inflammation in a Mouse Model of Metabolic Syndrome

“…lipid profiling results via LC-MS/MS (35,(37)(38)(39)(40)(41)(42)(43)(44). Our current study only evaluated transcriptional regulation of ALOX, future studies are needed to examine protein levels and activity.…”

“…MRM-profiling was originally proposed as a twophase (discovery and screening) method based on flow injection and chemical functional profiling for small molecule biomarker discovery (34,45). It has been applied to various studies (37)(38)(39)(40)(41)(42) and here, we used the approach to interrogate the samples for MRMs related to lipid mediators reported in the literature (46)(47)(48)(49). The ion intensities yielded were compared to a blank in order to eliminate the ones that were not informative.…”

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

“…The growth and development of an oocyte is a highly coordinated and complex biological process and largely dependent on surrounding granulosa and stromal cells. Interestingly, follicles isolated from aging mice ovaries show perturbations in gene expression and hormonal profiles and contain oocytes with diminished meiotic competence which is highlighted by a relatively higher incidence of spindle defects compared to their younger counterparts [67]. Indeed, the growth of granulosa cells has been considered as a crucial indicator of follicle development process.…”

“…It is also well-established that oocytes with declined quality are likely to have a significantly reduced competence for early embryonic development. This decline in quality is largely related to the age-related increase in occurrence of meiotic defects and is also likely to be compounded by additional cytoplasmic perturbations in key physiologic states in oocytes such as mitochondrial function and protein homeostasis [3], and possibly in the lipid profiles in peri-ovarian microenvironment [67]. Nevertheless, it is now well understandable that the decline in oocyte quality and competence is multifactorial and a wholistic and generalized perspective covering all developmental stages of oocytes is needed to fully elucidate the underlaying aging mechanisms [3].…”