Question

1. Compare the mouse estrus cycle to that of the human. Specifically, discuss hormones involved and patterns of cell morphology.
2. Discuss the brains role in the estrus cycle.

Answer 1

Reproductive processes in female mammals are characterised by cyclic alterations in the female tract and in sexual receptivity. The recurrent period of receptivity, or "heat" is called Estrus. The estrous cycle has been most extensively studied in laboratory rodents (mice and rats). Rats kept separate from males in the laboratory repeat the Estrous cycle throughout the year at intervals of about five days, unless subjected to pregnancy, pseudo-pregnancy (after a sterile mating), or disease. The cycle involves the whole of the reproductive tract, and it is possible to determine the sexual status of the female rat by examination of smears prepared from the vaginal fluid.Rats and mice are examples of polyestrus mammals (as are cats which are seasonally polyoestrus). Monestrus forms (most wild animals - foxes, bears, wolves etc.) complete a single estrous cycle annually. In the wild, rats and mice probably suspend the cycle for a period during the winter; the reproductive organs are in a state of quiescence, called anestrus.

Mouse Estrous Cycle

Stage	Ovary	Uterus		Smear
Diestrus	Small follicles only are present with large corpora lutea from the previous ovulation. These secrete for only a very short time unless pregnancy or pseudopregnancy intervene.	Small and anaemic, low motility, lumen small and slit-like. Cells of the uterine mucosa columnar; polymorphonuclear leucocytes in stroma; endometrial glands collapsed, atrophic.		Stringy mucous in which are entangled many leucocytes and a few nucleated epithelial cells.
Proestrus	Some follicles grow rapidly.	Become more vascular, water content increases, organ distends. Contractility more pronounced. Epithelial cells become higher (continuing into estrus). Leucocytes disappear from mucosa. Endometrial glands hypertrophy.		Largely small, round, nucleated epithelial cells, singly or in sheets. None to few leucoytes.
Estrus	Ovulation in the rat is spontaneous and occurs about 10 hours after the beginning of estrus. "Heat" (receptivity) lasts about 13 hours. Usually 10-20 eggs ovulated each time.	gains maximum vascularisation. Epithelial cells reach maximum development. No leucocytes.		Contains hundreds of large cornified cells (squames) with degenerate nuclei. Towards the end of estrus the smear becomes "cheesy" - masses of adherent cornified cells.
Metestrus	Many corpora lutea, which secrete only for a very short time, and small follicles.	Epithelium continues vacuolar degeneration and replacement. Leucocytes in stroma. Decrease in size and vascularity.		Many leucocytes and a few

Uterus The changes in the uterus may not be particularly well-marked.

1. Histological changes in the luminal epithelium
2. Histological changes in the glandular epithelium
3. Secretory activity of uterine glands
4. Changes in stromal cells, e.g. number of leucocytes
5. Overall changes in the size distention and shape of the lumen.

The estrus cycle is conserved regarding hormonal profiles but, whereas in humans is 28 days long, in mice lasts 4-5 days Estrus in mice and rats is also strictly linked to the 24 hours light-dark cycle.

Hippocampal Excitability Increases during the Estrous Cycle in the Rat: A Potential Role for Brain-Derived Neurotrophic Factor.Responsiveness to psychological stress in females ,The female brain, unlike its male counterpart, operates in a changing chemical milieu caused by cyclical changes in production of female sex hormones in the periphery during the menstrual cycle (estrous cycle in animals).

The female brain operates in a constantly changing chemical milieu caused by cyclical changes in gonadal hormones during the estrous cycle (menstrual cycle in women). Such hormones are highly lipophilic and pass readily from the plasma to the brain where they can influence neuronal function. It is becoming clear that the rapid reduction in peripheral circulating progesterone, which occurs during the late diestrous phase of the cycle, can trigger a withdrawal-like response, in which changes in GABAA receptor expression render hyper-responsive certain brain areas involved in processing responses to stressful stimuli.The periaqueductal gray matter (PAG) is recognised as an important region for integrating anxiety/defence responses. Withdrawal from progesterone, via actions of its neuroactive metabolite allopregnanolone, triggers up-regulation of extrasynaptic GABAA receptors on GABAergic neurons in the PAG. As a consequence, ongoing GABAergic tone on the output cells decreases,leading to an increase in functional excitability of the circuitry and enhanced responsiveness to stressful stimuli during the late diestrous phase. These changes during late diestrus could be prevented by short-term neurosteroid administration, timed to produce a more gradual fall in the peripheral concentration of allopregnanolone than the rapid decrease that occurs naturally thus removing the trigger for the central withdrawal response.