Maternal Recognition of Pregnancy - Anatomy & Physiology

Introduction

In most domestic species, maintenance of pregnancy requires prolonging the life of the corpus luteum/corpora lutea. As a result, progesterone concentrations remain elevated. This results in negative feedback on the hypothalamus and anterior pituitary gland, thus inhibiting follicular development and ovulation. In polyoestrous species, it prevents the return to oestrus. In many species, the placenta will take over or supplement the corpus luteum as the source of progesterone.

Overview

Species	Cow	Ewe	Sow	Mare	Queen	Bitch
Preganacy Recognition Factor	Bovine Interferon tau	Ovine Interferon tau	Oestrogen and Pituitary Prolactin	Unidentified	Pituitary Prolactin	None Required

Ruminants

• The free-floating blastocyst produces specific proteins that signal to prevent luteolysis.
• Sheep blastocysts produce ovine interferon tau (OIFN-τ)
• Cattle blastocysts produce bovine interferon tau (BIFN-τ)
• Interferon tau is a small protein produced by trophoblastic cells of the blastocyst.
• It is present in the uterus at day 13-21 after ovulation.
• It is not luteotrophic, so does not enhance progesterone production by the corpus luteum.
• Instead, it binds to the uterine endometrium and inhibits the synthesis of oxytocin receptors.
• In addition to preventing the upregulation of oxytocin receptors, interferon tau binds to the apical portion of uterine glands to promote synthesis of proteins that are critical for embryonic survival pre-implantation.
• As a result, there is no production of the luteolytic factor PGF2α and the corpus luteum is maintained.
• The corpus luteum then produces progesterone to maintain the pregnancy.

The Conceptus

• The ruminant conceptus undergoes rapid elongation between day 14 and 16.
• During this period, IFN-τ is secreted at high levels before decreasing.
• Small embryos produce much less IFN-τ than larger embryos.
• There is a hige proportion of embryo loss in the first 3 weeks of gestation, as small embryos fail to secrete enough IFN-τ in this critical period. Thus they do not block luteolysis.
  • This may be related to poor nutritional status of the mother.

Sow

• The pig conceptus produces oestradiol as the signal for maternal recognition of pregnancy.
• Also, PGF2α is produced in significant quantities, but is re-routed into the uterine lumen.
• Oestradiol is produced 11-12 days after ovulation. This does not inhibit secretion of PGF2α , but causes it to be secreted in a different direction than in a cycling sow.
• It is thought that prolactin production in the uterine endometrium increases under the influence of oestradiol. This acts to change the ionic flux for calcium, promoting exocrine secretion of PGF2α.
• It is secreted away from submucosal capillaries, towards the uterine lumen.
• Luminal PGF2α has little access to the circulation, and thus cannot cause luteolysis.
• Oestadiol also inactivates PGE2-9 oxoreductase,preventing the conversion of PGE2 to PGF2α.
• Production of oestradiol not only prevents luteolysis, but serves to stimulate contractions of the uterine myometrium. This ensures distribution of the conceptuses with proper spacing along the uterine horns.

Conceptus

• The secretion of oestradiol occurs in the period of conceptus elongation.
• There must be at least two conceptuses in each uterine horn for pregnancy to be maintained.
• If they are not present in one uterine horn, PGF2α will be secreted in an endocrine fashion and luteolysis will occur, thus terminating the pregnancy.

Mare

• The presence of a conceptus prevents luteolysis.
• In the presence of a conceptus, endometrial production of PGF2α is significantly reduced.
• The conceptus must migrate within the uterus from one uterine horn to the other 12-14 times a day during days 12, 13 and 14 of gestation in order to inhibit PGF2α.
• This migration is necessary, as the equine conceptus does not elongate, so there is less contact between the conceptus and the endometrial surface.
• It must move to distribute pregnancy recognition factors to the endometrial cells.
• The conceptus does produce proteins to effect the recognition of pregnancy, but specific roles are unknown.
• The luteolysin in the non-pregnanct cycle is thought to be PGF2α.

Conceptus

• The embryo takes 6 days to traverse the oviduct (in other species this is normally ~4 days). It stops at various spots in the uterus, spending 5-20 minutes in each.
• The conceptus remains spherical in shape.
• Day 6-22: the trophectoderm secretes a glycocalyx, which hardens to form a capsule.
  • This prevents attachment of the embryo to the uterine endometrium.
• Day 7-17: Peristaltic contractions of the uterine myometrium move the embryo around the uterus.
  • The conceptus begins to secrete oestrogens, but their role is unknown.
• Day 17: The myometrium clamps the embryo in position at the base of the uterine horns, preventing movement.
• If pregnant, upregulation of oxytocin receptors between day 10-16 is inhibited.

Bitch

• The corpus luteum of the cycle and the corpus luteum of pregnancy have similar lifespans.
• Under normal cyclic condition, the corpus luteum is long-lived.
• When luteolysis does occur, it is close to the end of the normal gestation period.
• Dioestrus is almost the same length as gestation.

Queen

• Induced ovulator, so if mating does not occur no corpora lutea will form.
• In this situation, a post-oestrus period of 8-10 days occurs before the next oestrus.
• In a queen that has been mated, corpora lutea form and their lifespan is the same as gestation (~60 days).
• Thus, corpora lutea do not undergo luteolysis before pregnancy is established.
• In the event of pseudopregnancy (mated without conception), once formed the corpora lutea last ~40 days.
• The lifespan of the corpora lutea in a pregnant queen is extended to ~60 days by the action of pituitary prolactin.
• There is no need for a conventional 'maternal recognition of pregnancy'.