Effects and Interactions of Early-Life and Adult Stress on Neuroendocrine Control of Reproduction
Gibson, Amanda
2024
Abstract
The neuroendocrine systems regulating stress and reproduction are important for organisms to respond to their environments and ensure the continuation of the species. Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus integrate many inputs and serve as the common central output to the downstream reproductive axis. The pulsatile release of GnRH leads to the synthesis and release of luteinizing hormone (LH) and follicle stimulating hormone from the anterior pituitary; these gonadotropins regulate the synthesis of sex steroids by the gonads. The frequency of GnRH/LH pulses changes throughout the ovarian reproductive cycle, and a high frequency of pulses in the preovulatory stage leads to a sustained rise in estradiol. This leads to a switch from negative to positive feedback effects of estradiol, inducing the LH surge and subsequent ovulation. The stress axis is organized similarly to the reproductive axis, beginning with corticotropin-releasing hormone (CRH) neurons in the hypothalamus. CRH stimulates the release of adrenocorticotropic hormone (ACTH) from the pituitary, and ACTH stimulates the synthesis of glucocorticoids by the adrenal glands. Both early-life and adult stress in humans can affect the reproductive system, and early-life stress may also change the response to adult stress. Because causal and mechanistic studies cannot be conducted in humans to understand these relationships, we used models for early-life and adult stress in rodents. Though the length of the reproductive cycle is different in humans and rodents, the pattern of hormonal changes is similar. We tested the hypotheses that limited bedding and nesting (LBN) from postnatal days 4-11 would delay sexual maturation in male and female mice, and would alter the response to an acute, layered, psychosocial stress (ALPS) in adulthood. ALPS disrupts the LH surge in most mice on proestrus. We also investigated a possible mechanism underlying ALPS disruption of the surge. LBN dams exited the nest more often than standard dams. Contrary to the hypotheses, however, the age and mass at vaginal opening, first estrus, and preputial separation were not affected by LBN. In males, diestrous females, and proestrous females, basal corticosterone (the primary glucocorticoid in rodents) concentrations were similar between standard and LBN reared mice. Further, ALPS increased serum corticosterone similarly in standard and LBN reared offspring. The LH surge was disrupted by ALPS in most mice when applied on the morning of proestrus, but this effect was not changed by LBN. To test if ALPS disrupts the LH surge by blunting the observed increase in excitatory GABAergic input to gonadotropin-releasing hormone (GnRH) neurons on the afternoon of proestrus, whole-cell voltage-clamp recordings were conducted following ALPS treatment. The frequency of GABA PSCs in GnRH neurons was not altered by LBN, ALPS, or their interaction. These studies suggested that LBN did not confer susceptibility or resilience to ALPS, and questions remain about how ALPS disrupts the LH surge. ALPS may act upstream of GnRH neurons, change the responsiveness of GnRH neurons to input, or decrease pituitary responsiveness to GnRH. We also tested and rejected the hypothesis that elevated serum corticosterone disrupts the LH surge and ovulation, as there were no differences between the incidence of the surge or ovulation between vehicle- and corticosterone-treated proestrous mice. Future studies should consider other potential mechanisms for ALPS-induced disruptions such as central actions of CRH or endogenous opioid peptide signaling.Deep Blue DOI
Subjects
reproduction stress GnRH LH surge early-life stress
Types
Thesis
Metadata
Show full item recordCollections
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.