repro

• There are three levels of sexual development: chromosomal (genetic) sex which is determined by chromosomes, gonadal sex – determined by presence of testes or ovary, and phenotypic sex (genitalia) – determined by gonadal hormones i.e. what does the animal look like externally.
• An early embryo with indifferent gonads will produce SRY gene if they have a Y chromosome. The SRY gene causes production of TDF and forms testes. Müllerian inhibitory substance ad testosterone are produced to form epididymis, vas deferens and accessory glands. If there is no TDF then ovaries will form. Lack of Müllerian inhibitory substance under influence of oestrogen allows formation of the oviduct, uterus, cervix and vagina
• The classification of differences of sexual development are by:

  • Sex chromosome type
  • Presence of SRY gene (sex determining region of Y chromosome)
  • Gonads
  • Tubular genitalia or external phenotype

  e.g. XY, SRY+, testicular DSD with female phenotype
• A trye hermaphrodite has both testicular and ovarian tissue. Genitalia are usually ambiguous but often predominantly female.

  A pseudohermaphrodite: Sex chromosomes and gonads are of one sex but the ducts and external genitalia are modified towards, or are of, the opposite sex. To class a pseudohermaphrodite as male or female you go with the sex of the GONADAL TISSUE
• A female pseudohermaphrodite will have ovarian tissue but a male or masculinised external genitalia.

  A male pseudohermaphrodite will have testicular tissue but female external genitalia
• A freemartin is a genetically female calf born twin with a male calf. During foetal development, placental anastomosis allows embryonic blood (including cells and hormones) to be shared and acquired (chimerism). As the testes develop earlier in embryonic life than ovaries, the TDF, MIS and testosterone enters the female twin’s circulation via the placental anastomosis and impairs normal female gonadal development.
• Morphological features of freemartins vary but may include:

  • Normal genitalia
  • Enlarged clitoris with long hair tufts around vulva
  • Hypoplastic, blind-ended vagina, vulva and vestibule
  • Uterus underdeveloped but vestigial vesicular glands present
  • Small mammary glands
  • stunted ovaries or ovotestis
• Congenital abnormalities of the ovaries:

  • Agenesis or duplication
  • Ovarian hypoplasia, often bilateral
  • Cysts, arising from mesonephric or paramesonephric ducts.
• Acquired pathology of the ovaries:

  • Cysts – may be:

  a.      Follicular where there has been failure to ovulate (LH release failure). May secrete oestrogen and can cause anoestrus, nymphomania, mammary hyperplasia

  b.      Luteinised where there is failure to ovulate but the cyst has a thicker wall. Usually no oestrogen but can cause infertility
• Haemorrhage in the ovaries (intrafollicular ovarian haemorrhage) may occur at ovulation from the corpus haemorrhagicum but can occasionally be severe or even fatal in mares.
• Inflammation of the ovaries (oophoritis) is rare but can be secondary to an ascending infection. Repair is by granulation tissue formation with fibrous adhesions to bursa.
• The clinical signs associated with cystic ovaries are:

  • Anoestrus and infertility
  • Nymphomania (increased libido)
  • Enlarged oedematous cervix
  • Cystic endometrial hyperplasia and mucometra (more nodules and mucus)
  • Mammary hyperplasia
  • Endocrine alopecia
• Ovarian neoplasias can arise in one of 3 ways:

  • From germ cells; either teratomas (multiple tissue types) or dysgerminoma (stay in a single cell line)
  • From gonadal stroma – granulosa cell tumour or granulosa theca cell tumour (most common in mare and cow). These produce more inhibin and MIS. Usually unilateral and benign
  • From surface epithelium – cystadenoma or adenocarcinoma. Demonstrate transcoelomic spread
• The two main conditions of the oviduct are:

  1.      Hydrosalpinx due to obstruction (congenital or acquired). The tubes distend with mucus secretions.

  2.      Salpingitis – inflammation from an ascending infection, especially in cattle. May affect fertility, often only detectable microscopically.
• Uterine congenita abnormalities include:

  • Agenesis – either bilateral or unilateral
  • Segmental aplasia – absence of part of or all the uterine horn.
  • Failure of fusion – of the uterine body and cervix or vagina
  • Failure of fusion of the uterus and urogenital sinus (imperforate hymen)
• Pathologies of the uterus fall under 6 categories:

  1.      Abnormal position or location

  2.      Endometrial changes

  3.      Inflammation

  4.      Cystic endometrial hyperplasia and pyometra

  5.      Miscellaneous

  6.      Neoplasia

   
• Abnormal positioning and location of the uterus can be:

  • Torsion – an enlarged uterus e.g. due to pregnancy or pyometra twists. Sequelae are congestion, oedema, foetal death and uterine rupture.
  • Prolapse – seen in cow, ewe and sow mostly. Usually post-partum and secondary to hypocalcaemia and prolonged dystocia. Sequelae are oedema, necrosis and shock.
  • Rupture – secondary to torsion or prolapse. Can be iatrogenic or due to untreated dystocia.
• Endometrial changes of the uterus can include:

  • Atrophy due to loss of ovarian function. Often an age-related change, secondary to hypopituitarism, anoestrus or following ovariectomy.
  • Hyperplasia – cystic endometrial hyperplasia, related to hormone influence e.g. granulosa cell tumours. Non-cystic hyperplasia also occurs in some species after ingestion of oestrogenic plants.
  • Endometrial polyps – seen in bitches and queens. Focal enlargement of the uterine horn with a pedunculated mass of stroma and dilated glands. Can prolapse through the cervix
  • Inflammation
• Inflammation of the uterus may be infectious or non-infectious and is influenced by hormones. The main routes of infection are via the cervix or haematogenous entry. Any infection may result in reduced fertility. Inflammation of the endometrium is endometriosis. Of the serosa is perimetritis. Of the whole wall is metritis. Endometriosis is chronic endometritis. Pyometra is chronic suppurative infection with accumulation of pus in the uterine lumen.
• Infection of the uterus at mating causes a mild non-specific endometritis which is usually rapidly cleared by neutrophils. Infected semen can also transmit infection following AI or natural infection e.g. contagious equine metritis (notifiable disease)- leads to purulent endometritis and cervicitis

   

  Postpartum infection can be via the vagina after parturition or abortion. There is increased risk in animals with dystocia, retained placenta or failure of involution
• Macroscopic inflammation of the uterus can range from slight opacity of oestral mucus (mild) to malodourous, grey brown uterine contents, sometimes with debris. The mucosa may be ulcerated, congested and haemorrhagic
• Sequalea of endometritis very widely:

  • Ascending infection
  • Descending infection (causing cystitis, pyelonephritis)
  • Septicaemia (fever, depression, death)
  • Embolic spread
  • Chronic endometritis (fibrosis, lymphoplasmacytic inflammation, glandular atrophy)
  • Pyometra
• Pyometra is an acute or chronic suppurative infection of the uterus with accumulation of pus in the uterine lumen (often a sequel to endometritis or metritis). This may be due to a persistent corpus luteum as there is failure of prostaglandin release. Can also be due to retained foetal membranes.
• Most dogs who develop pyometra are middle aged or old and have never been bred. Around 4-8 weeks after oestrus, there is inappetence, lethargy, vomiting, polyuria and polydipsia. There may also be uterine discharge.  pyrexia, neutrophilia and a painful/distended abdomen may also be noted.
• Cystic endometrial hyperplasia occurs in dioestrus due to oestrogen priming of the uterus, which is followed by progesterone. There is endometrial hyperplasia with dilated (cystic) glands, which can progress to pyometra, especially in bitches.
• Pathogenesis of cystic endometrial hyperplasia and pyometra:

  Oestrogen priming and elevated progesterone -> local irritation and inflammation -> cystic endometrial hyperplasia -> mucus secretion and secondary bacterial proliferation -> clinical pyometra -> systemic infection
• Macroscopically, cystic endometrial hyperplasia appears as distended uterine horns containing variable, often purulent content and congested serosal surfaces. Microscopically there is marked hyperplasia with cystic glands, inflammatory cells and congested blood vessels.
• Non-genital lesions of pyometra include toxaemia/ septicaemia, pre-renal azotaemia, polyuria, leucocytosis, myeloid hyperplasia of bone marrow and extra-medullary haematopoiesis.
• miscellaneous pathologies of the uterus:

  • Subinvolution of placental sites: postpartum, where the placenta was fails to involute, so there is persistent bloody discharge and necrotic placental tissue. Idiopathic
  • Hydrometra/ mucometra: accumulation of fluid or mucus in the uterus due to endometrial hyperplasia or and obstruction
• Uterine neoplasias:

  • Uterine carcinoma: seen in entire, older female rabbits
  • Leiomyoma – especially in bitches (smooth muscle neoplasia)
  • Lymphosarcoma
• Pathologies of the vagina and vulva:

  1.      Congenital defects – usually as part of DSD of failure of fusion  with the urogenital sinus

  2.      Swelling – may be a physiological change during oestrus or due to abnormal oestrogen levels

  3.      Trauma – prolapse or rupture

  4.      Fistulas – post dystocia. Can include the rectum.

  5.      Vulvovaginitis – due to infectious pustular vulvovaginitis (BHV-1 in cattle) or equine coital exanthema (EHV-3)
• Neoplasias of the vagina and vulva include:

  • Squamous cell carcinoma, due to solar radiation
  • Canine transmissible venereal tumour. Produces nodular, friable ulcerated lesions (microscopically sheets of round cells)
  • Melanotic tumours – seen in grey horses
  • Vaginal leiomyoma – single or multiple benign tumours
• Non-infectious conditions of the pregnant uterus:

  • Rupture (usually during parturition)
  • Ventral herniation
  • Adventitial placentation (formation of additional, less efficient sites of placentation between existing placentomes. If excessive can cause abortion)
  • Hydroamnios and hydroallantois
  • Prolonged gestation (due to foetal malformation e.g. no pituitary gland to initiate parturition)
  • Twinning (especially in mares)
  • Postpartum haemorrhage
  • Umbilical cord torsion
• General responses to disease during pregnancy:

  • Early embryonic death and resorption
  • Mummification – foetus dies but CL retained. Fluids resorbed, foetus retained
  • Maceration and emphysema – bacterial infection -> maceration -> resorption/expulsion. Dead foetal tissue invaded by gas-forming bacteria
  • Abortion
  • Stillborn (death within viable period)
  • Live birth – clinically normal or abnormal.
  • Congenital malformation of foetus
  • Retained foetal membranes -> metritis or endometritis
• Non-infectious causes of abortion:

  • Genetic defects
  • Nutrition (mycotoxins, plants)
  • Hyperthermia
  • Iatrogenic (drugs )
  • Trauma
  • Herpesvirus 1 is an infectious cause basically across species
• Infectious diseases of the pregnant uterus: pregnancy failure may occur as a result of:

  • Endotoxins or pyrexia with no lesions in the placenta or foetus (although bacteria present)
  • Immediate placentitis e.g. brucella abortus
  • Direct damage due to viruses e.g. BVDV, parvovirus; cause foetal death
• samples required to investigate an abortion outbreak:

  • Clinical history
  • Foetus – abortion or stillborn?
  • samples of placenta and foetus
  • dam: serum sample and uterine swab
  • placenta: submit whole or fresh and fixed samples
  • foetus: eyelid, brain, thyroid, thymus, lung, heart, liver, spleen, kidney, adrenal gland, intestine (or whole foetus)
• Causes of ovine abortion: TESTBLQC

  • toxoplasma
  • enzootic abortion (EAE caused by Chlamydophila abortus)
  • salmonella
  • tick borne fever
  • border disease
  • listeria
  • q-fever
  • campylobacter
• Mammary glands are composed of lobules of glandular tissue, made up of secretory units (alveoli) and their ducts in fibrofatty connective tissue. Myoepithelial cells control milk flow. Teat canals are lined with squamous epithelia.
• Congenital/ non-infectious conditions of the mammary gland:

  • Galactorrhoea: producing milk- can occur in the neonate via the dam’s hormones and in adults after parturition or false pregnancy
  • Malformations: mammary gland/ nipple aplasia, hypoplasia, inversion, non-patency. Significance depends on whether the animal will be used for breeding and milking
  • Supernumerary teats – can cause issues at milking, trauma, mastitis
  • Trauma – standing, catching, neonate biting, milking machine