Imaging and tracing the pattern of adult ovarian angiogenesis implies a strategy against female reproductive aging

Unique model of adult ovarian angiogenesis implies a strategy to extend female reproductive life span.

Age-associated changes in cumulus cells and follicular fluid: The local oocyte microenvironment as a determinant of gamete quality

The ovary is the first organ to age in humans with functional decline evident already in women in their early thirties. Reproductive aging is characterized by a decrease in oocyte quantity and quality which is associated with an increase in infertility, spontaneous abortions, and birth defects. Reproductive aging also has implications for overall health due to decreased endocrinological output. Understanding the mechanisms underlying reproductive aging has significant societal implications as women globally are delaying childbearing and medical interventions have greatly increased the interval between menopause and total lifespan. Age-related changes inherent to the female gamete are well-characterized and include defects in chromosome and mitochondria structure, function, and regulation. More recently, it has been appreciated that the extra-follicular ovarian environment may have important direct or indirect impacts on the developing gamete, and age-dependent changes include increased fibrosis, inflammation, stiffness, and oxidative damage. The cumulus cells and follicular fluid which directly surround the oocyte during its final growth phase within the antral follicle represent additional critical local microenvironments. Here we systematically review the literature and evaluate the studies that investigated the age-related changes in cumulus cells and follicular fluid. Our findings demonstrate unique genetic, epigenetic, transcriptomic, and proteomic changes with associated metabolomic alterations, redox status imbalance, and increased apoptosis in the local oocyte microenvironment. We propose a model of how these changes interact, which may explain the rapid decline in gamete quality with age. We also review the limitations of published studies and highlight future research frontiers.

Systemic L-ornithine supplementation specifically increases ovarian putrescine levels during ovulation in mice

In all mammalian species examined thus far, the ovaries produce a burst of ornithine decarboxylase (ODC) and putrescine during ovulation or after application of human chorionic gonadotropin (hCG). Aged mice have significantly reduced levels of this periovulatory ODC and putrescine rise. Putrescine supplementation, in vitro during oocyte maturation or in mouse drinking water during the periovulatory period, reduces egg aneuploidies and embryo resorption, improving fertility of aged mice. These studies suggest that periovulatory putrescine supplementation may be a simple and effective therapy for reproductive aging for women. However, putrescine supplementation is expected to increase widespread tissue putrescine levels, raising concerns of nonspecific and unwanted side effects. Given that ODC is highly expressed in the ovaries during ovulation but otherwise exhibits low activity in most tissues, we hypothesized that periovulatory supplementation of L-ornithine, the substrate of ODC, might be suitable for delivering putrescine specifically to the ovaries. In this study, we have demonstrated that systemic application of L-ornithine via oral gavage or subcutaneous injection increased ovarian putrescine levels; the increase was restricted to animals that had been injected with hCG. Furthermore, L-ornithine specifically increased ovarian putrescine levels without affecting putrescine levels in any other tissues. However, our attempts to improve fertility of aged mice through L-ornithine supplementation in mouse drinking water produced either no effects (1% L-ornithine) or negative impact on fertility (4% ornithine). Our results suggest that it might not be feasible to achieve fertility-enhancing ovarian putrescine levels via L-ornithine supplementation in drinking water without encountering undesired consequences of high dose of exogenous L-ornithine.

Understanding the Role of Semiochemicals on the Reproductive Behaviour of Cheetahs (Acinonyx jubatus)—A Review

The cheetah species (Acinonyx jubatus) is currently listed as vulnerable according to the International Union for Conservation of Nature (IUCN). Captive breeding has long since been used as a method of conservation of the species, with the aim to produce a healthy, strong population of cheetahs with an increased genetic variety when compared to their wild counterparts. This would then increase the likelihood of survivability once released into protected areas. Unfortunately, breeding females have been reported to be difficult due to the age of these animals. Older females are less fertile, have more difficult parturition, and are susceptible to asymmetric reproductive aging whereas younger females tend to show a significantly lower frequency of mating behaviour than that of older females, which negatively affects breeding introductions, and therefore mating. Nonetheless, the experience from breeding methods used in some breeding centres in South Africa and the Netherlands, which also rely on the role that semiochemicals play in breeding, proves that cheetahs can be bred successfully in captivity. This review aims to give the reader an in-depth overview of cheetahs’ reproductive physiology and behaviour, focusing on the role that pheromones play in this species. Furthermore, it aims to provide new insight into the use of semiochemicals to improve conservation strategies through captive breeding.

The Dynamic Regulation of mRNA Translation and Ribosome Biogenesis During Germ Cell Development and Reproductive Aging

The regulation of mRNA translation, both globally and at the level of individual transcripts, plays a central role in the development and function of germ cells across species. Genetic studies using flies, worms, zebrafish and mice have highlighted the importance of specific RNA binding proteins in driving various aspects of germ cell formation and function. Many of these mRNA binding proteins, including Pumilio, Nanos, Vasa and Dazl have been conserved through evolution, specifically mark germ cells, and carry out similar functions across species. These proteins typically influence mRNA translation by binding to specific elements within the 3′ untranslated region (UTR) of target messages. Emerging evidence indicates that the global regulation of mRNA translation also plays an important role in germ cell development. For example, ribosome biogenesis is often regulated in a stage specific manner during gametogenesis. Moreover, oocytes need to produce and store a sufficient number of ribosomes to support the development of the early embryo until the initiation of zygotic transcription. Accumulating evidence indicates that disruption of mRNA translation regulatory mechanisms likely contributes to infertility and reproductive aging in humans. These findings highlight the importance of gaining further insights into the mechanisms that control mRNA translation within germ cells. Future work in this area will likely have important impacts beyond germ cell biology.

Perimenopause and the Use of Fertility Tracking: 3 Case Studies

Perimenopause is a time in a woman's life where fertility may vary depending upon her age and her reproductive stage and has been defined as the transition period prior to menopause that is characterized by irregular menses, hormonal changes, vasomotor symptoms, and declining fertility (Casper, 2020). Fertility tracking during this time in a woman's reproductive stage has not been widely studied. Employing the use of Luteinizing Hormone Urine Assay sticks, an electronic hormonal monitor device or mucus, we propose a set of guidelines to determine the potentially fertile times of a woman's cycle based on staging according to the Stages of Reproductive Aging Workshop (STRAW) criteria and illustrate their application with three case reports.

PSX-A-24 Late-Breaking: Testosterone production by theca cells of large preovulatory follicles is affected by growth hormone depending on the hen age and the presence of granulosa cells

Testosterone produced by theca cells may be involved in regulating of the growth and ovulation of hen preovulatory follicles (Rangel, Gutierrez, Gen Comp Endocrinol, 203:250, 2014). In the current research, we studied effects of growth hormone (GH), a known regulator of the hen ovarian function, on in vitro testosterone production by the theca layer (TL) from the two largest yellow follicles in relation to the hen age and the presence of the granulosa layer (GL). Young hens with long clutch (YLC, 32–33 week-old, >10 eggs per clutch) and old hens with short clutch (OSC, 74–76 week-old, 3–6 eggs per clutch) were used. After isolation, TL from F1 and F2 follicles (n = 8–9) was cultured for 18 h in two systems, separately or together with the corresponding GL, in the presence or absence of chicken GH (25 ng/ml). Concentrations of testosterone in the spent media were measured by ELISA. The data were analyzed by RM-ANOVA. In the case of separate TL culture, GH did not change significantly testosterone production in both follicles of YLC hens and reduced it from 338±105 to 152±52 fmol/mg tissue (P < 0.05) in F1 follicles of OSC hens. When TL was cultured in the presence of GL, GH enhanced 1.8-2.6-fold (P < 0.05) the secretion of testosterone in the case of F1 follicles and decreased it 1.8-2.5-fold (P < 0.05) in the case of F2 follicles in both young and old hens. Regardless of the treatment, follicular size or culture system, the production of testosterone in OSC hens was 2–5 times higher than in YLC hens. The results indicate that the interaction between TL and GL changes the steroidogenic response of theca cells from preovulatory follicles to GH in young and old hens. Furthermore, testosterone production is obviously increased with reproductive aging of laying hens. The study was supported by RFBR (19-016-00216).

The influence of reproductive stage on cerebellar network connectivity across adulthood

Sex-specific differences in the aging cerebellum may be related to hormone changes with menopause. We evaluated the influence of reproductive stage on lobular cerebellar network connectivity using data from the Cambridge Centre for Ageing and Neuroscience repository. We used raw structural and resting state neuroimaging data and information regarding age, sex, and menopause-related variables. Crus I and II and Lobules V and VI were our cerebellar seeds of interest. We characterized reproductive stage using the Stages of Reproductive Aging Workshop criteria. Results show that postmenopausal females have lower cerebello-striatal and cerebello-cortical connectivity, particularly in frontal regions, along with lower connectivity within the cerebellum, compared to reproductive females. Postmenopausal females also exhibit greater connectivity in some brain areas as well. Differences begin to emerge across transitional stages of menopause. Further, results reveal sex-specific differences in connectivity between female reproductive groups and age-matched male control groups. This suggests that menopause may influence cerebellar network connectivity in aging females, and sex differences in the aging brain may be related to this biological process.