Reproductive physiology of female animals · Polyestrous = female cycles all year round (cow, pig, human, etc) Seasonal polyestrous = cycles in a particular season of the year Monoestrous

Reproductive physiology of

female mammals I-II.

László Solti, professor emeritus

University of Veterinary Medicine

Department of Reproduction

Introduction

What is reproduction?

Why is reproduction important?

Development and organization of

reproductive organs (female).

Cyclic function of the female

reproductive organs.

Reproduction:

a sequence of events

Development of the reproductive system in the embryo

The newborn animal must achieve puberty and acquiring the ability to produce fertile gametes

The animal must show reproductive behavior > estrous, libido, copulation, etc.

Fertilization > development of the early embryo > implantation > development of the fetus

Parturition > lactation (nourishment for the neonate)

Resumption of cyclicity > establishment of a newpregnancy

Reproductive terms

Andrology: deals with reproduction of male animals + humans (study/treatments of males)

Gynecology: deals with reproductive issues in woman

Theriogenology: deals with reproductive system of animals

Obstetrics: deals with the females before, during and after parturition in the human + animal

An International Journal

of Animal Reproduction

2. oldal, 1-es abra

Reproductive physiology:

wide area connected to

many fields

4. Oldal 1-2 abra

History of

reproductive

physiology

900 microscope

9 still in Utrecht

270X

Johann Ham, 1677

„animalcules”

Oocyte + spermatozoa

must be attached

Oocyte + spermatozoa

must be fused

Induced by seminal fluid

Importance of reproduction

The global challenge is to:

Decrease the rate of the growth of human population

The growth of the human population is cca. 300.000 per day

Increase the efficiency of the reproduction in food-producing animals > there is no production without reproduction!!!!

Educate the public about managing reproductive function in all species

Benefits of improved reproduction

Improvement in the reproductive rate is a major goal

in food animal production because a 3% increase

would result in:

1 million more beef calves/year

3.2 million more piglets/year

12.58 million L (3.7 million gallons) more milk annually

Litter size in swine

1 calf/13-14 months in dairy industry

1calf/year in beef industry

twin pregnancy in sheep

Development, anatomyand histology of the femalereproductive organs

Gonadal sex

In males, the sex is determined by the SRY protein, encoded by a gene, called sex determining region and located on the Y chromosome

Sertoli-cells produce anti-Müllerian factor (AMF) → Müllerian ducts

degenerate;

induce development of Leydig-cells

Leydig-cells produce testosterone which is partly converted into DHT by Sertoli-cells

In females, the SRY + Sertoli-cells are missing and there is no AMF production > Müllerian ducts stay intact + Wolffian ducts degenerate (no testosterone)

Sex and gender

Sex refers to the biological and physiologicalcharacteristics, while gender refers to behaviors, roles, expectations, and activities in societyExamples of characteristics related to sex:

Females have a vagina, men don't

Males have a penis, women don't

Male newborns tend to weigh more than female newborns

Females can breastfeed their babies, males can't

Males have deeper voices than females

Females can get pregnant, males can't

Males have testicles and females have ovaries

Examples of characteristics related to gender:

Women tend to do more of the housework than their spouses do

A higher percentage of US doctors are women, compared to Egypt

Nursing is often seen as a woman's job, although many men enter the profession

In some countries women have to cover their heads when they go outside the house

120 years ago women were not allowed to vote in elections

Insulin 3 >

descent of

the tesis

meiotic inhibiting factor(maintains meiotic arrest)

Introduction to Reproduction

anatomy

histology

endocrinology

regulation

The Organization and Function of

the Female Reproductive Tract

•Ovaries

•Oviducts

•Uterus

•Cervix

•Vagina

•External genitalia

Continuous

tubular

system

Female reproductive organs

Ovaries: gamete and hormone production

Oviducts: environment for fertilization + early

development of the preattachment embryos

Uterus: sperm transport + early embryonic

development + attachment of the embryo/fetus

Cervix: barrier + mucus production

Vagina: mucus production + copulatory organ

External genitalia (perineal area)

Structure

The female tract is a series of tubes (oviducts,

uterus, cervix and vagina) and each of them is

organized in concentric layers:

Serosa (outer)

Muscularis

Submucosa

Mucosa (inner)

Wall structure of thereproductive tract

Senger: Pathways to pregnancy and parturition (3rd ed)

Surrounded by peritoneum (very outer layer)

which continues in the broad ligament

• The broad ligament (BL) (ligamentum latum uteri) houses the blood vessels,nerves, lymphatic drainage;• BL develops from theperitoneum• Mesovarium (aroundovaries)• Mesosalpinx (aroundoviduct)• Mesometrium (arounduterus)

Advanced Duplex

(Opossum)

Two Uterine

Horns

Two Cervices

Two Vaginas

Duplex

(Rabbit, Mouse)

Two Uterine

Horns

Two Cervices

One Vagina

Bicornuate

(Pig)

Two Uterine

Horns (long)

Common

Uterine Body

One CervixOne Vagina

Bipartite

(Cow, Ewe, Doe)

Smaller

Uterine Horns

Modified Bipartite

(Mare)

Larger Uterine

Body with Smaller

Uterine Horns

Simplex

(Human)

No Uterine

Horn, All

Uterine

Body

Types of internal genital organs

Placenta types (histological)

Placentome in Ruminants

Cow

Chorion

Caruncle

Endometrium

Chorion

Caruncle

Endometrium

Ewe

Mare, SowChorion

Microcotyledon

Endometrium

Placentomes




Ovarian

bursa

Mesosalpinx

completely covers

the ovaries



Ovarianstructures

Estrogen

Inhibin

FSH

receptors

Maturation of the

oocytes

P4 + oxytocin, relaxin, inhibin, activin

AndrogensLH receptors

Corpus hemorrhagicum„bloody body”


9/7/2015

Ovulationand CL

formation


Ovulationfossa

• Ovarian medulla and cortex are reversed• F can but CL cannotbe palpated

F and CL can be palpated rectally

Histologicalstructure of the oviduct

Mucosal folds > Fimbriae

Ostium

Uterotubal junction >Regulate the movementof the embryo(s) into theuterus

Finger-like projections =fimbriae


9/7/2015

Structure of the uterus

Serosa/perimetrium

Muscularis/myometrium

Mucosa + submucosa/endometrium


Functions of the uterus

Sperm transport

Luteolysis and control of cyclicity

Environment for preattachment embryo

Feeding the embryos and spermatozoa;

(enhance embryo development and

sperm viability)

Maternal contribution to the placenta

Expulsion of the fetus and fetal placenta

Structure of

the cervix

The cervix provides:

• a flushing system,

- mucose production

(lubrication + protection)

• a barrier

- controlling sperm transport

- isolation – protection

- cervical seal (viscous

mucus) during pregnancy


Histologicalstructure of the

cranial/caudalvagina

Highly secretory

High E2 > thickening >

1) mechanical protection +

2) prevents microorganism

immigration

Sperm deposition:

Ruminants/carnivores > intravaginal

Pig > intracervical

Horse > intrauterine


Anatomy of the hypothalamus, pituitary and pineal gland

Hormonal regulation of the

female reproductive cycle

Cyclic function of the ovaries

and the reproductive tract

Tonic and surge centersin the hypothalamus

Senger: Pathways to pregnancyand parturition (3rd ed)

GnRH-patterns

from the tonic

and surge center


The hypothalamo-

pituitary portalsystem

Connection between

HYP and adeno-hypophysis


Connection

between HYP and

neurohypophysis

No portal system!!!!

Milk let down is a neuroendocrine reflex


Neural Reflex

9/7/2015

Prenatal „defeminization” of the malebrain and it’s consequences (no surge

center in males, consequently, thehormonal profiles differ between the

two sexes)


Kisspeptin neuronsintegrate various inputs

Kisspeptins are neuropeptides

Secreted by HYP neurons

Stimulate GnRH secretion


Role of kisspeptin neurons inthe regulation of seasonalcyclicity in long-day and

short-day breeders

Circadian rhythm

„For their discoveries of molecular

mechanisms controlling the

circadian rhythm"

Internal biological clock.Mimosa plants have a cell autonomous clock that can maintain the biological rhythm even under constant conditions (d’Ortous de Mairan, 1729) Feedback regulation of the period gene

The circadian clock has an impact on our physiology

Basal GnRH-pulse frequencyis elevated after puberty


Gonadotropindependency of different tertiary

follicles

Effects of E2 and inhibin on thehypothalamus and pituitary


Wave-like pattern of folliculardevelopment in the cow


9/7/2015

Follicularwaves

The „two cell-twogonadotropin” model of estrogenproduction of tertiary follicles


Induced

ovulation


Cyclicity profile of qeens

(induced ovulator)

PGF2α bound to lutealreceptors induces apoptosis


Effects of

progesterone

Senger: Pathways to pregnancyand parturition (3rd ed)

Progesterone primes the brainfor the effects of estradiol


1. Hormone receptor binding2. Activation of adenylate cyclase3. Protein kinase activation4. Synthesis of new product


Fast response1. Steroid binding to

membrane receptors2. Activation of adenylate

cyclase3. Protein kinase activation4. Synthesis of new product

Slow response1. Steroid transport2. Movement through the

cell membrane and cytoplasm

3. Binding of steroid tonuclear receptor

4. mRNA synthesis and protein synthesis

Types of reproductive cycles

Length of the cycle: sheep 16-17 d, most mammals 20-21 d, primates 28-37 d

Receptive/receptivity = accepts the male for mating

Polyestrous = female cycles all year round (cow, pig, human, etc)

Seasonal polyestrous = cycles in a particular season of the year

Monoestrous = has only 1 or 2 cycle in a year

Anestrous/lactational anestrous = pregnancy/lactation (beefcattle, pig, human)

No lactational anestrus = mare (1 week), dairy cow (3 weeks), small ruminants/dogs (longer time) > postpartum resumption of cyclic ovarian function

Small cycle = estrous cycle

Big cycle = from fertilization (pregnancy, parturition, lactation, resumption of cyclic ovarian function) to the next fertilization

Types of oestrous cycles

(E2 profiles)

Seasonality

Cyclicity is in connection with daylength > melatonin(M) production by the pineal gland

Long day breeders: decreased M induces cyclicity(horse)

Short day breeders: increased M induces cyclicity(sheep, goat)

Monoestrus: 1 or 2 cycle/year; spring period (dog)

Anestrus: physiological (pregnancy, lactation, seasonality, dog has long anestrus (4-6 months)

Pathological causes: stress, endometritis, systemicdisease, ovarian tumor, energy deficit, starvation, etc.

Seasonality

• Circannual species (small ruminants, deer, somerodents)

They have biological clock, which induces cyclicity aroundthe same time of the year

• Not circannual species (mice, rat)

Continues photostimulation can maintain cyclicity all yeararound regardless of the season

• Light programs

Can be used in order to induce earlier the cyclicity in theyear

• Melatonin implant is used in small ruminants in orderto induce cycling in non-breeding season

Melovine implant (18 mg melatonin)

Chronogest vaginal sponge

Day 0. Sponge/implant introduced

Day 12-14. Removal of sponge/implant + 400-500 IU eCG

+ 24 hr vasectomized ram in

+ 48 hr AI with fresh semen, or

+ 53-58 hr AI frozen semen

Types of reproductive cycles

1. Estrous cycle: 21 (17) days long

Estrus > female shows behavioral changes + observable signs of heat > accepts themale for copulation; Day 0 is the time of estrus

2. Menstrual cycle: 28 (37) days longSpecific sign > mestrual bleeding (menses)Day 0 is the mensesPrimates (+ humans) + elephant have

this type of cycle

Menstrual cycle (MC) in general

Onset of MC (menstrual periods)

OWM: 4 years of age (rhesus)

Great apes: 8-10 (in captivity: 6-7) years of age

Human: 11-14 years of age

But: genetical factors, nutrition, climate

Duration of MC

Orangutans: 29 days (4-6 days)

Baboon: 32 days (3-4 days)

Gorillas: 30 days (2-3 days)

Chimpanzee: 37 days (10-14 days)

Woman: 28 days (4-7 days)

Big individual differences

Estrous cycle

Phases of the estrous cycle


Stages of the estrous cycle

Dog = 9 days

Cow = 1 D

Mare = 5-7 D

Sow = 3 D

Dog = 2 months


Menstrual cycle

Differences

between the

estrous and

menstrualcycles


Mitotic and meiotic divisonsof oogonies and the oocyte

Senger: Pathways topregnancy and

parturition (3rd ed)

Main hormones in

female reproduction

Main hormones in the

regulation of reproduction

P4

Dehydroepiandrosterone, androstenedion, testosterone

E2

Inhibin, activin

PGF2α

Relaxin

Insulin, IGF-2, leptin

Prolactin

FSH, LH, eCG, hCG

Oxytocin, GnRH

Melatonin

Melatonin is regulated by light


Melatonin

Structure: amino acid derivate

Site of synthesis: Pineal gland (dark hours of the day)

Precursor: produced through many steps from tryptophan

Synthesis:

light stimulation → retina > transmitted through the optic nerve to thesuprachiasmatic nucleus > an inhibitory neuron is stimulated > noradrenergic neurons will be blocked > pinealocytes will not be stimulated > melatonin production ↓;

during dark hours the activity of the inhibitory neuron ↓> norepinephrin + melatonin production ↑

Role in reproduction: regulation of the seasonality of reproduction;

Regulation of the GnRH production and release

Long-day breeders (horse): light > melatonin production ↓ > GnRH ↑

Short-day breeders (sheep): decreasing light stimulation result in increasing melatonin production/release

Oxytocin and GnRH

Structure:

1) Oxytocin consists of 9 amino-acid (peptide);

2) GnRH consists of 10 amino-acid (decapeptide) > neuropeptides

Synthesis:

1) oxytocin is produced in HYP > paraventricular nucleus,

and is released into blood vessels in the neuro-hypophysis

2) GnRH is produced in the HYP > tonic and surge centers

Oxytocin is also produced by the CL (luteolyses)

Half-life of both hormones are very short!!!

Role in reproduction: smooth muscle contraction, follicular

development, luteolysis, etc.

Pituitary (FSH, LH) and extrapituitary (eCG, hCG)

gonadotropins

Structure: glycoprotein hormones (α and β peptid

chain); the α chain is the same in all four hormones

Site of synthesis: FSH/LH → adenohypophysis; eCG

(PMSG) → endometrial cups, Days 35-140; hCG →

trophoblast cells in the human embryo

Receptors: FSH → granulosa cells of tertiary F3; LH

→ granulosa cells of dominant F - luteal cells of CL

eCG → FSH receptors; hCG → LH receptors

Prolactin (PRL)

Structure: Protein hormone

Site of synthesis: lactotroph cells in the anterior pituitary,

regulated by dopaminergic neurons of HYP (dopamin

inhibits PRL release)

Role in reproduction: together with growth hormone, E2 and P4 stimulates the development of mammaryglands; induces milk production + placental lactogensecreted by placenta; in dogs it has a luteotropiceffect (supports CL); negative effect on the activity of GnRH neurons (dog, human); high PRL decreaseslibido (e.g. lactating mothers)

Progesterone

(P4)

Structure: steroid hormone

Site of synthesis: Luteal cells of the CL and the placenta

Synthesis: cholesterol – pregnenolon – P4

Transport in the blood: P4 is in complex withtranscortin/albumin

Metabolism: excreted in the urine and/or faces after hydroxy-

lation and conjugation with glucuronic acid or sulfate

Cholesterol Pregnenolone

Progesterone

P4 + synthetic derivates =

gestagens

Dehydroepiandrosterone(DHEA), androstenedion,

testosteroneStructure: steroid hormones > androgenes

Site of synthesis: theca cells, follicles;

DHEA + androstenedion in adrenal cortex too;

They can be aromatized into E2 in the ovaries.

Precursor of synthesis: androstenedion can be

synthesized from pregnenolone through P4 or

DHEA, then it is further converted into testosterone

Testosterone dihydrotestosterone

Transport (blood): in complex with globulin SHBG

Metabolism: converted into E2, then conjugated

with glucuronic acid/sulfate, secreted into urine

DHEA

Androstenedione

Testosterone

5α-reductase

Estradiol (E2)

Structure: steroid hormone

Site of synthesis: granulosa cells of the tertiary follicles + placenta

Precursor of the synthesis: androgens, aromatisation

by the aromatase enzyme, conversion of androgens

into E2

Transport (blood): SHBG + albumin

Metabolism: Estradiol converted into less potentestrone

(E1) or estriol (E3), then conjugated with glucuronic

acid/sulfate, secreted into urine!! or feces

Inhibin, activin

Structure: protein hormones, built up from two chains and belong

to the family of transforming growth factors (TGFs)

Site of synthesis: granulosa cells of dominant follicles + placenta.

Inhibin is also synthesized by the luteal cells of CL

Role in reproduction: activin receptor, activin – FSH ↑ + follicular

growth; inhibin – FSH ↓

Vaccination against inhibin: FSH ↑, # of preovulatory follicles ↑

Fecundity genes in Booroola breeds (FecB, FecX) decrease the

inhibin level

# of twin pregnancies ↑

Prostaglandin F2α

Structure: arachidonic acid derivative

Site of synthesis: endometrial tissue

Role in reproduction:

- luteolysis,

- smooth muscle contraction (myometrium) > promotes involution

- side effects (intestines, blood vessels) > horse

- half life: 30 sec

Prostaglandin E2 (PGE2)

It has role in ovulation (in every species)

Dog: produced by CL, autocrine

luteotrophic factor beside PRL

Horse: supports the migration of the

embryos (relaxes the smooth muscle!!)

Relaxin

Structure: protein hormone

Site of synthesis: CL and placenta

Role in reproduction: relaxes the uterine smooth

muscles (except the last few weeks), supports

pregnancy, relaxes the pelvic ligament, softens the

cervix and widens the pelvic bones before

parturition

In canine, the relaxin is pregnancy specific → indicates

pregnancy

Pregnancy determination in canine: US + relaxin test

Insulin, IGF-2, leptin

Structure: protein hormones

Site of synthesis:

- Insulin: B-cells of pancreatic Langerhans-islets;

- IGF-2 (insulin-like growth factor 2): hepatocytes +

ovarian theca cells (induced by growth hormone);

- Leptin: mature adipocytes

Role in reproduction:

- Insulin + leptin are indicators of the nutritional status;

- Leptin takes part in the induction of puberty stimulatesGnRH-release (well fed females show cyclicity);

- IGF-2 takes part in the regulation of follicular growth

Documents

Reproductive physiology of female animals · Polyestrous = female cycles all year round (cow, pig, human, etc) Seasonal polyestrous = cycles in a particular season of the year Monoestrous