From Iusmphysiology

• started here on 04/08/11.

Contents 1 Pregnancy, parturition, and lactation 1.1 Learning objectives 1.2 Pregnancy 1.2.1 Female anatomy review 1.2.2 Fertilization 1.2.2.1 Sperm transport 1.2.2.2 Capacitation 1.2.2.3 Ovum transport 1.2.3 Events of fertilization 1.2.3.1 Twinning 1.2.4 Fertilization to implantation 1.2.5 Methods of contraception 1.2.6 Implantation 1.2.7 Structure of the placenta 1.2.8 Function of the placenta 1.2.9 Endocrinology of pregnancy 1.2.10 Human chorionic gonadotropin 1.2.11 Human placental lactogen 1.2.12 Steroid hormones of pregnancy 1.2.13 Endometriosis 1.2.14 Maternal changes of pregnancy 1.3 Parturition 1.3.1 Role of placental CRH 1.4 Lactation 1.4.1 Development of the mammary glands 1.4.2 Anatomy of the breast 1.4.3 Lactogenesis 1.4.4 Role of prolactin 1.4.5 Role of suckling 1.4.6 Role of oxytocin 1.4.7 Characteristics of human milk 1.4.8 Sustaining lactation 1.5 Summary

Pregnancy, parturition, and lactation

Learning objectives

• Understand the processes of fertilization and implantation
• Understand the structure and function of the placenta
• Be familiar with the endocrine changes that occur during pregnancy
• Understand key concepts of parturition
• Understand key concepts of lactation

Pregnancy

Female anatomy review

• The female reproductive tract is composed of gonads that generate gametes and a series of ducts that maintain the gametes and the fetus.
• The gonads are the ovaries, found bilaterally and suspended from the posteriolateral wall of the abdomen by the ovarian ligaments.
• The beginning of the duct system is the fallopian tube (oviduct) which catches the evicted ocum via fimbria and passes it to the uterus via the ampulla and isthmus divisions.
• The uterus has a fundus, corpus, and cervix; the inside surface of the corpus is the endometrium which is the location of implantation and the connection point between mother and child during pregnancy.
• The cervix connects to the vagina.

Fertilization

• Fertilization is defined as the successful union of sperm and an egg.
• For fertilization to occur, both the egg and the sperm must be rapidly transported to their union because they each have a lifespan of only 2 days.
  • Sperm transport through the female reproductive tract is best facilitated during the follicular phase; more to the point, sperm travels best through the female reproductive tract during the proliferative stage of the uterine cycle.
  • Recall that the proliferative stage of the uterine cycle is characterized by endometrial hypertrophy and formation of spiral arteries.
• For proper fertilization, fresh sperm must be present as the ovum enters the oviduct (Fallopian tube).

Sperm transport

• About 250 million sperm are released upon ejaculation, however, only 50 million will make it to the oviduct.
  • Loss of sperm is due to: acidic pH of the vagina, phagocytosis of sperm in the uterus, and the anatomical barrier presented by the uterotubal junction (that is, where the isthmus of the oviduct dumps into the uterus is a small opening that the sperm must find and proceed through).
  • Sperm arrive at the oviduct in less than 5 minutes!
  • That's about 0.5 sperm body lengths / second.
• Sperm are able to move through the female ducts because of their own motility and because of assisting vaginal, cervical, and uterine contractions.
• Semen initially coagulates (bad for transport) in the ducts and then liquefies (good for transport).
• During the follicular phase, mucin molecules of the cervical canal are oriented in parallel to facilitate transport of the sperm.

Capacitation

• Recall the basic anatomy of the sperm: three parts (head, middle, tail), an acrosome (sac of enzymes in the head), a nucleus, mt, and a tail (axoneme).

• Capacitation is a series of irreversible changes occurring in the sperm as a result of being delivered to the female reproductive ducts.
• Capacitation results in increased motility and happens after an hour of being delivered to the ducts.
• Changes during capacitation include: loss of surface proteins and lipids and merging of acrosome with cell membrane.

Ovum transport

• Recall that during ovulation, the oocyte of the dominant follicle is ejected from the ovary.
• Recall the basic anatomy of the follicle: many layers, theca x 2, granulosa, antrum, fluid, corposa oophorus, corona radiata, zona pellucida.
• The ejection of the egg leaves leaves the theca and granulosa layers to become the corpus luteum
  • This makes sense when one recalls that the corpus luteum will go on to be the primary source of hormones and the granulosa cells and theca cells generate estrogen / progesterone and androgens, respectively.
• The ejected egg will therefore be composed of the cumulus oophorus, the zona pellucida, and the cell body of the oocyte.
• This oocyte is collected into the fallopian tube (oviduct) by way of ciliary action of the fibria.

• Some additional oocyte anatomy:
  • The oocyte has three pre-cellular layers as it encouters sperm: the cumulus oophorus and corona radiata surrounding the zona pellucida.
  • Deep to the zona pellucida is the perivitelline space that separates the zona pellucida and the oolemma (the cell membrane of the oocyte).
  • The oocyte also has a series of microvilli just underneath the oolemma, which are poised to be an important part of the egg's interaction with sperm.
  • Finally, recall that the first polar body will exist with the oocyte within the protective encasing of the cumulus oophorus, corona radiata, and zona pellucida.

Events of fertilization

• Fertilization takes place in the ampulla of the oviduct.
  • Recall that 50 million sperm have made it to the oviduct and 1 egg has been moved into the oviduct via ciliary action of the fimbria.
  • Recall that the sperm has undergone capacitation to make it a better swimmer and to merge its acrosome with the cell membrane at the tip of the head section.
  • Recall that the egg that makes it to the oviduct is covered by the cumulus oophorus, the corona radiata, the zona pellucida, the perivitelline space, and the oolemma.
• The process of fertilization can be view as the solution to two major tasks: 1) getting through the layers surrounding the oocyte to the cell body and 2) keeping multiple sperm from fertilizing the oocyte.

• Getting through the protective layers of the oocyte:
• When the sperm and egg unite, the sperm breaks through the cumulus oophorus and the corona radiata to adheres to the zona pellucida of the egg.
  • Adherence of the sperm to the zona pellucida is mediated by the ZP3 receptor.
• Adherence to the zona pellucida triggers release of the enzymes of the acrosome.
• Enzymes of the acrosome digest the cumulus oophorus.

I don't understand how binding the zona pellucida can cause release of enzymes that digest the cumulus oophorus when the oophorus is superficial to the zona pellucida.

• • The sperm penetrate the zona pellucida in about 15-30 minutes.
• Once through the zona pellucida, sperm cross the perivitelline space (space between the zona pellucida and the cell membrane of the oocyte).
• Upon adhering to the oolemma (cell membrane of the oocyte), microvilli of the oocyte extend to grasp the sperm and the spermatic head and tail are engulfed.

Really?  I think it has been shown that the tail is very specifically NOT engulfed.

• Keeping multiple sperm from fertilizing the oocyte:
• Once the oocyte has grasped the first sperm to penetrate the zona pellucida, the egg undergoes changes to the oolemma that prevent other sperm from entering the cell.
• Penetration of the first sperm through the oolemma causes Ca to enter the cell and two processes to begin: cortical granule release and the completion of meiosis 2.
  • Rising Ca levels cause cortical granule fusion with the oolemma.
  • As the cortical granules fuse the zona pellucida undergoes changes such that we call it the zona reaction, which is impermeable to sperm.
  • As meiosis 2 completes, a single oocyte nucleus (1N) remains.

• Finally, a zygote is generated by the fusion of the male and female pronuclei.

What's the 2-3 degree about?

Twinning

• Twinning occurs in 3% of live births.
• There are two types of twinning: monozygotic and dizygotic.
  • Monozygotic twinning occurs when one zygote splits into two separate, functional embryos and generates identical twins.

Fertilization to implantation

• The first mitotic division of the embryo occurs within 24-36 hours of fertilization.
  • This initial cell division occurs in the oviduct, near the site of fertilization.
• Note that the embryo continues to be surrounded by the zona pellucida for the first several division generations for several reasons:
  • transport, protection, and inhibition of immune reactions.
• As the fertilized egg travels along the oviduct it will undergo mitosis and form into a solid ball of cells called a morulla.
  • The morulla enters the uterus approximately 4 days after fertilization.

Is this after ovulation or after fertilization?

• It is possible that an egg can become fertilized outside of the female reproductive tract resulting in an ectopic pregnancy.
  • Ectopic pregnancies can be life-threatening if not treated.

Methods of contraception

Implantation

• The process of implantation is about physically attaching to the endometrium and establishing communication between the embryo and the mother's vascular system.
  • A blastocyst implants in the endometrial wall of the uterus at approximately 7 days after fertilization and is fully embedded by 8-12 days post-ovulation.
• A blastocyst is a collection of 20-30 cells that have two distinct regions (the trophoblast and the embryoblast) with a fluid filled center.
  • The trophoblast will go on to become all the extraembryonic tissue like the plaenta and umbilical cord.
  • The embryoblast (inner cell mass) will go on to become the fetal tissue.
• The cells of the trophoblast commence the process of implantation by using proteases to invade the endometrium.

Is there a consistent location within the uterus for implantation?  Does the location of the placental attachement change along the way?  Does it effect parturition?

• The trophoblasts embedded in the endometrium differentiate into two cell populations to facilitate development of communication between the embryo and the mother's vascular system.
  • Cytotrophoblasts: become villi and eventually chorionic villi.
  • Syncytiotrophoblasts serve to increase the surface area for embryo-mother interaction and also secrete progesterone and hCG.
• Upon trophoblast invasion, the endometrium becomes undergoes changes to become a decidua in a process called the decidual reaction.
  • The maintenance of the decidua requires progesterone from the luteal cells of the corpus luteum and the synciotrophoblasts.
  • The decidua is characterized by large, polyhedral, multinucleated cells, dilated blood vessles, and lacunae.
• Eventually, the embryo will be composed of the three embryological tissue types: ectoderm, endoderm, and mesoderm.

Structure of the placenta

• After implantation, the trophoblast offspring (cytotrophoblasts and synciotrophoblasts) interdigitate with endometrial cells to form chorionic villi and lobes called cotyledons.

Function of the placenta

Endocrinology of pregnancy

Human chorionic gonadotropin

Human placental lactogen

Steroid hormones of pregnancy

• includes "role of progesterone and estrogen"

Endometriosis

• Recall that endometrial cells line the inside of the uterus and respond to estrogen and progesterone by proliferation.
• When endometrial cells exist outside of the uterus (like on the ovaries), they can proliferate and cause pathology.
  • S&S include pelvic pain that worsens with the menstruation cycle.
  • It makes sense that pain would increase during during the follicular uterine cycle and the luteal phase of the ovarian cycle because estrogen levels will be high.
• Endometriosis is in 5-10% of women--usually during the reproductive years.
• Endometriosis is a common cause of infertility.

Maternal changes of pregnancy

• includes "progesterone and estrogen"

Parturition

Role of placental CRH

Lactation

Development of the mammary glands

Anatomy of the breast

Lactogenesis

Role of prolactin

Role of suckling

Role of oxytocin

Characteristics of human milk

Sustaining lactation

Summary

• stopped here on 04/07/11.